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Play Episode Listen Later Oct 31, 2024 18:03

Dr. Ryan Augustin and Dr. Jason Luke discuss neoadjuvant immunotherapy and the importance of multidisciplinary team coordination, promising new TIL therapy for advanced melanoma, and the emerging role of CD3 engagers in treatment strategies. TRANSCRIPT Dr. Ryan Augustin: Hello, I'm Dr. Ryan Augustin, your guest host of the ASCO Daily News Podcast today. I'm a medical oncology fellow at Mayo Clinic in Rochester, Minnesota. Joining me today is Dr. Jason Luke, an associate professor of medicine and the director of the Cancer Immunotherapeutic Center at the University of Pittsburgh Hillman Cancer Center. I had the privilege of working as a postdoc in Jason's translational bioinformatics lab, where we investigated mechanisms of resistance to immunotherapy in melanoma and other cancers. Today, we'll be discussing 3 important topics, including neoadjuvant immunotherapy and the importance of multidisciplinary team coordination, the impact and practical considerations for incorporating TIL therapy into melanoma, and the current and future use of CD3 engagers in both uveal and cutaneous melanoma. You'll find our full disclosures in the transcript of this episode. Jason, it's great to have this opportunity to speak with you today. Dr. Jason Luke: Absolutely. Thanks, Ryan. It's great to see you. Dr. Ryan Augustin: So, to kick things off, Jason, we, of course, have seen tremendous advances in cancer immunotherapy, not only in metastatic disease but also the perioperative setting. Recent data have shown that the use of neoadjuvant therapy can provide not only critical prognostic information but can also help individualize post-resection treatment strategies and potentially even eliminate adjuvant therapy altogether in patients who achieve a pathologic, complete response. This signifies a conceptual shift in oncology with the goal of curing patients with immunotherapy. In triple-negative breast cancer, the KEYNOTE-522 regimen with pembrolizumab is standard of care. In non-small cell lung cancer, there are now four FDA approved chemo-IO regimens in both the neoadjuvant and perioperative settings. And, of course, in melanoma, starting with SWOG S1801 utilizing pembro mono therapy, and now with combined CTLA-4 PD-1 blockade based on results from the NADINA trial, neoadjuvant IO is the new standard of care in high-risk, resectable melanoma. It's important to highlight this because whereas other tumor types have more mature multidisciplinary care, for example, patients with breast cancer are reviewed by the whole team in every center, and every patient with lung cancer certainly benefits from multidisciplinary care conferences, that's not always the case with melanoma, given the relative frequency of cases compared to other tumor types. Jason, would you say that we have now moved into an era where the integration of a multidisciplinary team and melanoma needs to be prioritized. And why is it important to have multidisciplinary team coordination from the onset of a patient's diagnosis? Dr. Jason Luke: Well, I think those are great questions, Ryan, and I think they really speak to the movement in our field and the great success that we've had integrating systemic therapy, particularly immunotherapy, into our treatment paradigms. And so, before answering your question directly, I would add even a little bit more color, which is to note that over the last few years, we've additionally seen the development of adjuvant therapy into stages of melanoma that, historically speaking, were considered low-risk, and medical oncologists might not even see the patient. To that, I'm speaking specifically about the stage 2B and 2C approvals for adjuvant anti-PD-1 with pembrolizumab or nivolumab. So this has been an emerging complication. Classically, patients are diagnosed with melanoma by either their primary care doctor or a dermatologist. Again, classically, the next step was referral to a surgeon who had removed the primary lesion, with discussion around nodal evaluation as well. And that paradigm has really changed now, where I think integration of medical oncology input early on in the evaluation of the appropriate treatment plan for patients with melanoma is quite a pressing issue now, both because we have FDA approvals for therapeutics that can reduce risk of recurrence, and whether or not to pursue those makes a big difference to the patient for discussion early on. And, moreover, the use of systemic therapies now, prior to surgery, of course, then, of course, requires the involvement of medical oncology. And just for an emphasis point on this, it's classically the case, for good reason, that surgeons complete their surgery and then feel confident to tell the patient, “Well, we got it all, and you're just in really good shape.” And while I understand where that's coming from, that often leaves aside the risk of recurrence. So you can have the most perfect surgery in the world and yet still be at very high risk of recurrence. And so it's commonly the case that we get patients referred to us after surgery who think they're just in totally good shape, quite surprised to find out that, in fact, they might have a 20% to 50% risk of recurrence. And so that's where this multidisciplinary integration for patient management really does make a big difference. And so I would really emphasize the point you were making before, which is that we need multidisciplinary teams of med onc with derm, with surgery early on, to discuss “What are the treatment plans going to be for patients?” And that's true for neoadjuvant therapy, so, for palpable stage 3, where we might give checkpoint inhibitors or combinations before surgery. But it's true even in any reasonably high-risk melanoma, and I would argue in that state, anything more than stage 1 should be discussed as a group, because that communication strategy with the patient is so important from first principles, so that they have an expectation of what it's going to look like as they are followed out over time. And so we're emphasizing this point because I think it's mostly the case at most hospitals that there isn't a cutaneous oncology disease management meeting, and I think there needs to be. It's important to point out that usually the surgeons that do this kind of surgery are actually either the GI surgeons who do colon cancer or the breast surgeons. And so, given that melanoma, it's not the most common kind of cancer, it could easily be integrated into the existing disease review groups to review these cases. And I think that's the point we really want to emphasize now. I think we're not going to belabor the data so much, but there are enormous advantages to either perioperative or adjuvant systemic therapy in melanoma. We're talking about risk reduction of more than 50%, 50-75% risk reduction. It's essential that we make sure we optimally offer that to patients. And, of course, patients will choose what they think is best for their care. But we need to message to them in a way that they can understand what the risks and benefits of those treatments are and then are well set up to understand what that treatment might look like and what their expectations would be out over time. So I think this is a great art of medicine place to start. Instead of belaboring just the details of the trial to say, let's think about how we take care of our patients and how we communicate with them on first principles so that we can make the most out of the treatments that we do have available. Dr. Ryan Augustin: That's great, Jason. Very insightful points. Thank you. So, shifting gears now, I'd also like to ask you a little bit about TIL therapy in melanoma. So our listeners will be aware that TIL is a promising new approach for treating advanced melanoma and leverages the power of a patient's cytotoxic T cells to attack cancer cells. While we've known about the potential of this therapy for some time, based on pioneering work at the NCI, this therapy is now FDA approved under the brand AMTAGVI (Lifileucel) from Iovance Biotherapeutics, making it the first cellular therapy to be approved for a solid tumor. Now, I know TIL therapy has been administered at your institution, Jason, for several years now, under trial status primarily for uveal melanoma using an in-house processing. But for many cancer centers, the only experience with cellular therapy has come under the domain of malignant hematology with CAR T administration. At our institution, for example, we have only recently started administering TIL therapy for melanoma, which has required a tremendous multidisciplinary effort among outpatient oncology, critical care, and an inpatient hematology service that has expertise in cytokine release syndrome. Jason, where do you see TIL therapy fitting into the metastatic space? Which patients do you think are truly candidates for this intensive therapy? And what other practical or logistical considerations do you think we should keep in mind moving forward? Dr. Jason Luke: Well, thanks for raising this. I think the approval of lifileucel, which is the scientific name for the TIL product that's on the market now. It really is a shift, a landscape shift in oncology, and we're starting in melanoma again, as seems to be commonly the case in drug development. But it's really important to understand that this is a conceptually different kind of treatment, and therefore, it does require different considerations. Starting first with data and then actualization, maybe secondarily, when we see across the accelerated approval package that led to this being available, we quote patients that the response rate is likely in the range of 30%, maybe slightly lower than that, but a meaningful 25% to 30% response rate, and that most of those patients that do have response, it seems to be quite durable, meaning patients have been followed up to four years, and almost all the responders are still in response. And that's a really powerful thing to be able to tell a patient, particularly if the patient has already proceeded through multiple lines of prior standard therapy. So this is a very, very promising therapy. Now, it is a complicated therapy as well. And so you highlighted that to do this, you have to have a tumor that's amenable for resection, a multidisciplinary team that has done a surgery to remove the tumor, sent it off to the company. They then need to process the TIL out of the tumor and then build them up into a personalized cell product, bring it back, you have to lympho-deplete the patient, re-introduce this TIL. So this is a process that, in the standard of care setting under best circumstances, takes roughly six weeks. So how to get that done in a timely fashion, I think, is evolving within our paradigms. But I think it is very important for people who practice in settings where this isn't already available to realize that referring patients for this should be a strong consideration. And thinking about how you could build your multidisciplinary team in a way to be able to facilitate this process, I think is going to be important, because this concept of TIL is relevant to other solid tumors as well. It's not approved yet in others, but we kind of assume eventually it probably will be. And so I think, thinking through this, how could it work, how do you refer patients is very important. Now, coming back to the science, who should we treat with this? Well, of course, it's now an air quotes “standard of care option”, so really it ought to be available to anybody. I will note that currently, the capacity across the country to make these products is not really adequate to treat all the patients that we'd want. But who would we optimally want to treat, of course, would be people who have retained a good performance status after first line therapy, people who have tumors that are easily removable and who have not manifested a really rapid disease progression course, because then, of course, that six-week timeline probably doesn't make sense. The other really interesting data point out of the clinical trials so far is it has looked like the patients who got the least amount of benefit from anti-PD-1 immunotherapy, in other words, who progressed immediately without any kind of sustained response, those patients seem to have the best response to TILs, and that's actually sort of a great biomarker. So, this drug works the best for the population of patients where checkpoint inhibitors were not effective. And so as you think about who those patients might be in your practice, as you're listening, I think prioritizing it for primary progression on anti PD-1, again and giving it ahead thought about how would you get the patient through this process or referred to this process very quickly is really important because that lag time is a problem. Patients who have melanoma tend to progress reasonably quickly, and six weeks can be a long time in melanoma land. So, thinking ahead and building those processes is going to be important moving into the future Dr. Ryan Augustin: Definitely appreciate those practical considerations. Jason, thank you. Moving on to our final topic, I was hoping to discuss the use of immune cell engagers in melanoma. So, similar to CAR T therapy, bispecific T-cell engagers, or BiTEs, as they're commonly known, are standard of care in refractory myeloma and lymphoma. But these antibodies engaging CD-3 on T cells and a tumor specific antigen on cancer cells are relatively new in the solid tumor space. Tarlatamab, which is a DLL-3 and CD-3 bispecific antibody, was recently approved in refractory small cell lung cancer, and, of course, tebentafusp, an HLA-directed CD-3 T cell engager was approved in uveal melanoma in 2022. Both T and NK cell engaging therapies are now offering hope in cancers where there has historically been little to offer. However, similar to our discussion with TIL therapy, bispecifics can lead to CRS and neurotoxicity, which require considerable logistical support and care coordination. Jason, I was wondering if you could briefly discuss the current landscape of immune cell engagers in melanoma and how soon we may see these therapies enter the treatment paradigm for cutaneous disease. Dr. Jason Luke: I think it is an exciting, novel treatment strategy that I think we will only see emerge more and more. You alluded to the approval of tebentafusp in uveal melanoma, and those trials were, over the course of a decade, where those of us in solid tumor land learned how to manage cytokine release syndrome or the impact of these C3 bispecifics, in a way that we weren't used to. And what I'll caution people is that CRS, as this term, it sounds very scary because people have heard of patients that, of course, had difficult outcomes and hematological malignancies, but it's a spectrum of side effects. And so, when we think about tebentafusp, which is the approved molecule, really what we see is a lot of rash because GP100, the other tumor antigen target, is in the skin. So, patients get a rash, and then people do get fevers, but it's pretty rare to get more than that. So really what you have to have is the capacity to monitor patients for 12 hours, but it's really not more scary than that. So it really just requires treating a few people to kind of get used to these kinds of symptoms, because they're not the full-on ICU level CRS that we see with, say, CAR T-cells. But where is the field going? Well, there's a second CD3 bispecific called brenetafusp that targets the molecule PRAME, that's in a phase 3 clinical trial now for frontline cutaneous melanoma. And tebentafusp is also being evaluated in cutaneous melanoma for refractory disease. So, it's very possible that these could be very commonly used for cutaneous melanoma, moving into, say, a two-to-four-year time horizon. And so therefore, getting used to what are these side effects, how do you manage them in an ambulatory practice for solid tumor, etc., is going to be something everyone's going to have to learn how to deal with, but I don't think it should be something that people should be afraid of. One thing that we've seen with these molecules so far is that their kinetics of treatment effect do look slightly different than what we see with more classic oncology therapies. These drugs have a long-term benefit but doesn't always manifest as disease regression. So, we commonly see patients will have stable disease, meaning their tumor stops growing, but we don't see that it shrank a lot, but that can turn into a very meaningful long-term benefit. So that's something that we're also, as a community, going to have to get used to. It may not be the case we see tumors shrink dramatically upfront, but rather we can actually follow people with good quality- of-life over a longer period of time. Where is the field going? You mentioned tarlatamab in small cell lung cancer, and I think we're only going to see more of these as appropriate tumor antigens are identified in different tumors. And then the other piece is these CD3 engagers generally rely upon some kind of engagement with a T cell, whether CD3 engagers, and so they can be TCR or T-cell receptor-based therapies, although they can be also SCFV-based. But that then requires new biomarkers, because TCR therapy requires HLA restriction. So, understanding that now we're going to need to profile patients based on their germline in addition to the genomics of the tumor. And those two things are separate. But I would argue at this point, basically everybody with cutaneous melanoma should be being profiled for HLA-A(*)0201, which is the major T-cell receptor HLA haplotype that we would be looking for, because whether or not you can get access immediately to tebentafusp, but therefore clinical trials will become more and more important. Finally, in that T-cell receptor vein, there are also T cell receptor-transduced T cells, which are also becoming of relevance in the oncology community and people listening will be aware in synovial sarcoma of the first approval for a TCR-transduced T cell with afamitresgene autoleucel. And in melanoma, we similarly have TCR-transduced T cells that are coming forward in clinical trials into phase 3, the IMA203 PRAME-directed molecule particularly. And leveraging our prior conversation about TILs, we're going to have more and more cellular based therapies coming forward, which is going to make it important to understand what are the biomarkers that go with those, what are the side effect profiles of these, and how do you build your practice in a way that you can optimally get your patients access to all of these different treatments, because it will become more logistically complicated, kind of as more of these therapies come online over the next, like we said, two to four years kind of time horizon. So, it's very exciting, but there is more to do, both logistically and scientifically. Dr. Ryan Augustin: That's excellent. Thanks, Jason, and thank you so much for sharing your great insight with us today on the ASCO Daily News Podcast. Dr. Jason Luke: Thanks so much for the opportunity. Dr. Ryan Augustin: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode, and you can follow Dr. Luke on X, formerly known as Twitter, @jasonlukemd. And you can find me, @RyanAugustinMD. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers: @ryanaugustinmd Dr. Jason Luke @jasonlukemd Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Ryan Augustin: No relationships to disclose Dr. Jason Luke: Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof) Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

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DESTINY-Breast06 and A-BRAVE: Advances in Breast Cancer Research

Play Episode Listen Later Aug 8, 2024 15:12

Dr. Allison Zibelli and Dr. Erika Hamilton discuss the results of the DESTINY-Breast06 trial in HR+, HER2-low and HER2-ultralow metastatic breast cancer and the A-BRAVE trial in early triple-negative breast cancer, the results of which were both presented at the 2024 ASCO Annual Meeting. TRANSCRIPT Dr. Allison Zibelli: Hello, I'm Dr. Allison Zibelli, your guest host of the ASCO Daily News Podcast. I'm an associate professor of medicine and breast medical oncologist at the Sidney Kimmel Cancer Center of Jefferson Health in Philadelphia. My guest today is Dr. Erika Hamilton, a medical oncologist and director of breast cancer research at the Sarah Cannon Research Institute. We'll be discussing the DESTINY-Breast06 trial, which showed a progression-free advantage with the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) compared to chemotherapy in hormone receptor-positive HER2-low or HER2-ultralow metastatic breast cancer. We'll address the implications of this study for the community, including the importance of expanding pathology assessments to include all established subgroups with HER2 expression, and the promise of expanding eligibility for antibody-drug conjugates. We'll also highlight advances in triple-negative breast cancer, focusing on the A-BRAVE trial, the first study reporting data on an immune checkpoint inhibitor avelumab in patients with triple-negative breast cancer with invasive residual disease after neoadjuvant chemotherapy. Our full disclosures are available in the transcript of this episode. Erika, it's great to have you on the podcast today. Dr. Erika Hamilton: Thanks so much, Allison. Happy to join. Dr. Allison Zibelli: Antibody-drug conjugates are rapidly changing the treatment landscape in breast cancer. The data from the DESTINY-Breast06 trial suggests that trastuzumab deruxtecan may become a preferred first-line treatment option for most patients with HER2-low or HER2-ultralow metastatic breast cancer after progression on endocrine therapy. First, could you remind our listeners, what's the definition of HER2-ultralow and what were the findings of this trial? Dr. Erika Hamilton: Yeah, those are fantastic questions. Ultralow really has never been talked about before. Ultralow is part of a subset of the IHC zeros. So it's those patients that have HER2-tumor staining that's less than 10% and incomplete but isn't absolutely zero. It's even below that +1 or +2 IHC that we have classified as HER2-low. Now, I think what's important to remember about D-B06, if you recall, D-B04 (DESTINY-Breast04) was our trial looking at HER2-low, is that D-B06 now included HER2-low as well as this HER2-ultralow category that you asked about. And it also moved trastuzumab deruxtecan up into the frontline. If you recall, D-B04 was after 1 line of cytotoxic therapy. So now this is really after exhausting endocrine therapy before patients have received other chemotherapy. And what we saw was an improvement in progression-free survival that was pretty significant: 13.2 months versus 8.1 months, it was a hazard ratio of 0.62. And you can ask yourself, “well, was it mainly those HER2-low patients that kind of drove that benefit? What about the ultralow category?” And when we look at ultralow, it was no different: 13.2 months versus 8.3 months, hazard ratio, again, highly significant. So I think it's really encouraging data and gives us some information about using this drug earlier for our patients with hormone receptor-positive but HER2-negative disease. Dr. Allison Zibelli: I thought this study was really interesting because it's a patient population that I find very difficult to treat, the hormone receptor-positive metastatic patient that's not responding to endocrine therapy anymore. But it's important to mention that T-DXd resulted in more serious toxicities compared to traditional chemotherapy in this study. So how do you choose which patients to offer this to? Dr. Erika Hamilton: Yeah, those are both great points. So you're right, this is after endocrine therapy. And in fact, about 85% of these patients had received at least 2 prior lines of endocrine therapy. So I have some people kind of asking, “Well, if endocrine therapy really isn't benefiting everyone in the second-line setting post-CDK, should we just move to the ADCs?” And, no, probably we should really make sure that we're exhausting endocrine therapies for those patients that are going to benefit. And once we determine somebody has endocrine-resistant disease, that's when we would think about switching. In terms of the side effects, I think you're right. It's mainly ILD that's probably the more serious side effect that we worry about a little bit with trastuzumab deruxtecan. The good news is, through multiple trials, we've gotten a little bit better at managing this. We've pretty much all but eliminated any fatal cases of ILD, definitely less than 1% now. ILD rates, depending on what study you look for, kind of ranges in that 10% to 15% range. Any grade ILD on D-B06 was 11.3%. So really kind of making sure that we look for ILD at scans, making sure that patients are educated to tell us about any new pulmonary symptoms: cough, exertional dyspnea, shortness of breath at rest, etc. But I think the most common side effects that we really deal with on a daily basis with trastuzumab deruxtecan, luckily, is nausea, which we've gotten better at managing with the 2- or 3-drug antiemetic regimen, and probably a little bit of fatigue as well. Dr. Allison Zibelli: Thank you. So, I think for most people in the community, the sticking point here will be expanding pathology assessments to include all of the subgroups, including the ultralow. Most patients in the community are not testing for HER2-low and HER2-ultralow now. Dr. Erika Hamilton: Historically, we kind of all did HER2 IHC, right? And then as FISH became available, there were a lot of institutions that moved to FISH and maybe didn't have IHC anymore. And now, at least in my institution, we do both. But I think it's a very important point that you made that IHC was really designed to pick out those patients that have HER2-high, the 3 pluses or the FISH amplified cases. It was not to tell the difference between a 1+ or a 2+ or a 0 that's not quite a 0 and a 1+. So I think you're right. I think this is tough. I probably have a little bit more of an interesting take on this than some people will. But data from ASCO, not this year but in 2023, there was actually a pretty eloquent study presented where they looked at serial biopsies in patients, and essentially, if you got up to 4 or 5 biopsies, you were guaranteed to have a HER2-low result. Now, this didn't even include ultralow, which is even easier. If we know we include ultralow, we're really talking about probably 85% to 90% of our patients now that have some HER2 expression. But if we biopsy enough, we're guaranteed to get a HER2 low. And so I think the question really is, if we know IHC wasn't really designed to pick out these ultralows, and we know kind of greater than 90% of patients are going to have some expression, did we kind of develop this drug a little bit backwards? Because we thought we understood HER2, and the reality is this drug is a little bit more like a sacituzumab govitecan, where we don't test for the TROP2. Should we really be kind of serial biopsying these patients or should maybe most patients have access to at least trying this drug? Dr. Allison Zibelli: So I don't think that most of my patients will really be happy to sign up for serial biopsies. Dr. Erika Hamilton: Agreed. Dr. Allison Zibelli: Do we have any emerging technologies for detecting low levels of HER2? You talked about how the IHC test isn't really designed to detect low levels of HER2. Do you think newer detection techniques such as immunofluorescence will make a difference, or will we have liquid biopsy testing for this? Dr. Erika Hamilton: Yeah, I think liquid biopsy may be a little bit hard, just because some of those circulating tumor cells are more of a mesenchymal-type phenotype and don't necessarily express all of the same receptors. Normally, if they're cytokeratin-positive, they do, but certainly there is a lot out there looking at more sensitive measures. You mentioned immunofluorescence, there are some even more quantitative measures looking at lower levels of HER2. I definitely think there will be. I guess, ultimately, with even the IHC zeros that are the less than 10% incomplete staining, having a PFS that was absolutely no different than the HER2 low, I guess the question is, how low can we really go? We know that even the IHC zeros doesn't mean that there's no HER2 expression on the cell surface. It just means that maybe there's a couple of thousand as opposed to 10,000 or 100,000 copies of HER2. And so it really appears that perhaps this drug really is wedded to having a lot of HER2 expression. So ultimately, I wonder how much we're going to have to use those tests, especially with what we know about tumor heterogeneity. We know that if we biopsy 1 lesion in the liver, biopsy a lymph node, or even another lesion in the liver, that the HER2 results can have some heterogeneity. And so ultimately, my guess is that most people have some HER2 expression on their breast cancer cells. Dr. Allison Zibelli: So maybe we're going to be using this for everybody in the future. Dr. Erika Hamilton: It certainly seems like we keep peeling back the onion and including more and more patients into the category that are eligible to receive this. I agree. Dr. Allison Zibelli: Let's move on to triple-negative breast cancer, namely the A-BRAVE trial. This was an interesting trial for patients that did not get neoadjuvant immunotherapy and testing 2 groups. The first group was those with residual disease after neoadjuvant conventional chemotherapy. The second group was people with high-risk disease identified upfront that had upfront surgery. The study found that adjuvant avelumab did not improve disease-free survival versus observation, which was the study's primary endpoint. But interestingly, there was a significant improvement in 3-year overall survival and distant disease-free survival. Can you give us your thoughts on that? Dr. Erika Hamilton: Yeah, I think this study was really interesting. Right now, the standard for our patients with larger or node-positive triple-negative cancers is KEYNOTE-522. It's a pretty tough regimen. It's kind of 2 sequential uses of 2 chemotherapies, so 4 chemotherapy agents total with pembrolizumab. But you're right, this study looked at those that had residual disease after neoadjuvant that didn't include immunotherapy, or those patients that didn't get neoadjuvant therapy, went to surgery, and then were receiving chemotherapy on the back end. I'm going to give you the numbers, because you're right. The 3-year disease-free survival rates were not statistically significant. It was 68.3% among those that had avelumab, 63.2% with those that had observation only. So the difference was 5.1% in favor of avelumab, but it wasn't statistically significant. A p value of 0.1, essentially. But when we looked at the 3-year overall survival rates, we saw the same pattern, those patients with the avelumab doing better, but it was 84.8% overall survival and not, unfortunately, dying, versus 76.3%. So the magnitude of benefit there was 8.5%, so about 3% higher than we saw for disease-free survival, and this was statistically significant. So is this going to change practice for most patients? I probably don't think so. I think for our patients that have larger tumors that's recognized upfront or have node positivity, we're probably going to want to use neoadjuvant chemo. Being able to get a PCR is very prognostic for our patients and enables us to offer things on the back end, such as PARP inhibitors or further chemotherapy of a different type of chemotherapy. But for our patients that go to surgery and maybe the extent of their disease just isn't recognized initially, this could be an option. Dr. Allison Zibelli: I agree. I think this will be a really useful regimen for patients where we get the surprise lymph node that we weren't expecting, or somebody who comes to us, maybe without seeing the medical oncologist, who got upfront surgery. So I thought this was really interesting. What kind of translational studies do you think we're going to do to try and understand which patients would benefit from avelumab? Dr. Erika Hamilton: Yeah, I think that's a great question, and honestly, it's a question that we haven't really answered in the neoadjuvant setting either. Immunotherapy in breast cancer is just a little bit different than it is in some other diseases. We have a benefit for those patients that are PD-L1 positive in the first line. We really haven't seen benefit for metastatic outside of first line. And then in neoadjuvant, it was among all comers. We don't have to test for PD-L1. And now we have this avelumab data from A-BRAVE. I think the question is, is there's probably a subset of patients that are really getting benefit and a subset that aren't. And I don't know that PD-L1 testing is the right test. We know a lot of people are looking at TILs, so kind of lymphocytes that are infiltrating the tumor, a variety of other kind of immunologic markers. But my guess is that eventually we're going to get smart enough to tease out who actually needs the immunotherapy versus who isn't going to benefit. But we're not quite there yet. Dr. Allison Zibelli: Thank you, Erika, for sharing your valuable insights with us on the ASCO Daily News Podcast today. Dr. Erika Hamilton: Thanks so much for having me. Dr. Allison Zibelli: And thank you to our listeners for joining us. You'll find the links to all the abstracts discussed today in the transcript of this episode. Finally, if you like this podcast and you value our insights, please take a moment to rate, review, and subscribe wherever you get your podcasts. It really helps other people to find us. So thank you very much for listening today. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers: Dr. Allison Zibelli Dr. Erika Hamilton @ErikaHamilton9 Follow ASCO on social media: @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn   Disclosures: Dr. Allison Zibelli: None Disclosed Dr. Erika Hamilton: Consulting or Advisory Role (Inst): Pfizer, Genentech/Roche, Lilly, Daiichi Sankyo, Mersana, AstraZeneca, Novartis, Ellipses Pharma, Olema Pharmaceuticals, Stemline Therapeutics, Tubulis, Verascity Science, Theratechnologies, Accutar Biotechnology, Entos, Fosun Pharma, Gilead Sciences, Jazz Pharmaceuticals, Medical Pharma Services, Hosun Pharma, Zentalis Pharmaceuticals, Jefferies, Tempus Labs, Arvinas, Circle Pharma, Janssen, Johnson and Johnson Research Funding (Inst): AstraZeneca, Hutchison MediPharma, OncoMed, MedImmune, Stem CentRx, Genentech/Roche, Curis, Verastem, Zymeworks, Syndax, Lycera, Rgenix, Novartis, Millenium, TapImmune, Inc., Lilly, Pfizer, Lilly, Pfizer, Tesaro, Boehringer Ingelheim, H3 Biomedicine, Radius Health, Acerta Pharma, Macrogenics, Abbvie, Immunomedics, Fujifilm, eFFECTOR Therapeutics, Merus, Nucana, Regeneron, Leap Therapeutics, Taiho Pharmaceuticals, EMD Serono, Daiichi Sankyo, ArQule, Syros Pharmaceuticals, Clovis Oncology, CytomX Therapeutics, InventisBio, Deciphera, Sermonix Pharmaceuticals, Zenith Epigentics, Arvinas, Harpoon, Black Diamond, Orinove, Molecular Templates, Seattle Genetics, Compugen, GI Therapeutics, Karyopharm Therapeutics, Dana-Farber Cancer Hospital, Shattuck Labs, PharmaMar, Olema Pharmaceuticals, Immunogen, Plexxikon, Amgen, Akesobio Australia, ADC Therapeutics, AtlasMedx, Aravive, Ellipses Pharma, Incyte, MabSpace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pieris Pharmaceuticals, Pionyr, Repetoire Immune Medicines, Treadwell Therapeutics, Accutar Biotech, Artios, Bliss Biopharmaceutical, Cascadian Therapeutics, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, Relay Therapeutics, Tolmar, Torque, BeiGene, Context Therapeutics, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Cullinan Oncology, Bristol-Myers Squib, Eisai, Fochon Pharmaceuticals, Gilead Sciences, Inspirna, Myriad Genetics, Silverback Therapeutics, Stemline Therapeutics

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Immunotherapy at ASCO24: NADINA and Other Key Studies

Play Episode Listen Later Jun 19, 2024 34:51

Dr. Diwakar Davar and Dr. Jason Luke discuss advances in the neoadjuvant immunotherapy space that were presented at the 2024 ASCO Annual Meeting, including promising outcomes in high-risk melanoma from the NADINA trial, as well as other new treatment options for patients with advanced cancers. TRANSCRIPT Dr. Diwakar Davar: Hello and welcome to the ASCO Daily News Podcast. I'm your guest host, Dr. Diwakar Davar, and I am an associate professor of medicine and the clinical director of the Melanoma Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. I am delighted to have my colleague and friend Dr. Jason Luke on the podcast today to discuss key late-breaking abstracts and advances in immunotherapy that were presented at the 2024 ASCO Annual Meeting. Dr. Luke is an associate professor of medicine, the associate director of clinical research, and the director of the Cancer Immunotherapeutic Center at the University of Pittsburgh Hillman Cancer Center. You will find our full disclosures in the transcript of this episode. Jason, it's always a pleasure to hear your insights on the key trials in these spaces and to have you back as a guest on this podcast that highlights some of the work, especially advances, that were just presented. Dr. Jason Luke: Well, thanks very much for the invitation. I always love joining the podcast. Dr. Diwakar Davar: We'll start very quickly by talking about some advances and really interesting things that happened both in the context of melanoma but also in immunotherapy in general. And we'll start with what I think was certainly one highlight for me, which was LBA2, the late-breaking abstract on the NADINA trial. It was featured in the Plenary Session, and in this abstract, Dr. Christian Blank and colleagues reported on the results of this phase 3 trial of neoadjuvant ipi-nivo. This is the flipped dose of ipi1/nivo3 versus adjuvant nivolumab in PD-1 naive, macroscopic, resectable, high-risk stage 3 melanoma. By way of background, neoadjuvant immunotherapy for those listening is an area of increasing interest for drug developers and development for both approved and novel agents. Neoadjuvant immunotherapy has been studied with multiple approved agents, including PD-1 monotherapy, PD-1 LAG-3, PD-1 CTLA-4, T-VEC, as well as investigational agents and multiple randomized and non-randomized studies. The benchmark pathologic response rates with these agents range from 17% PCR with PD-1 monotherapy, 45% to 55% PCR with PD-1 CTLA-4 combination therapy, and slightly higher 57% PCR with PD-1 LAG-3 has recently reported by Dr. Rodabe Amaria from MD Anderson. However, as we embark on phase 3 comparisons for various neoadjuvant compared to adjuvant immunotherapy trials and combinations, we're increasingly moving towards event-free survival as the primary endpoint for neoadjuvant versus adjuvant studies. And this was most recently studied in the context of SWOG S1801, a study that was led by Dr. Sapna Patel. So, Jason, before we start on NADINA, can you briefly summarize the SWOG S1801 trial and the event-free survival statistic reported by Dr. Patel and her colleagues? Dr. Jason Luke: Well, absolutely. And these data were reported at ESMO about two years ago and then in the New England Journal last year. The S1801 study answered a very simple question: What would happen if you took three of the doses of standard adjuvant therapy with pembrolizumab and moved them prior to surgery? And on a high level, the study is as simple as that. And many of us were somewhat skeptical of this trial design because we thought that just moving the doses earlier may not actually have a major impact. In the study, you alluded to the event-free survival statistic, and that alludes to what was considered an event. And so, without reading all of it, there were several different aspects that were included in terms of time, based on the date of randomization until the first of a series of events, such as disease progression, toxicity from treatment, if the patient was unable to go to surgery or had surgical complications, or if they had delay in starting the adjuvant therapy due to toxicity, and obviously, recurrence of melanoma or death from any cause. In that context, merely moving the 3 doses of pembrolizumab to the neoadjuvant setting saw an improvement in this two-year event free survival to 72% for the neoadjuvant therapy compared to 49% for the adjuvant therapy. That was quite an outstanding change. And again, noting the power of neoadjuvant treatment, really dictating the impact of anti PD-1, again, just with 3 doses moving from adjuvant into the neoadjuvant setting, and I think all of us were somewhat surprised to see that magnitude of a benefit. But it set up the current study very well, where we now look at combination therapy. Dr. Diwakar Davar: So let's move on to the phase 3 NADINA trial. Do you want to perhaps discuss the study design, particularly focusing on the EFS primary endpoint and maybe also touching on the different schedules? So, SWOG S1801 was a neoadjuvant study of 3 cycles of pembrolizumab and how did that compare and contrast to the neoadjuvant combination that was studied in NADINA? Dr. Jason Luke: Well, as you alluded to, NADINA investigated the regimen of nivolumab plus ipilimumab and compared that against adjuvant therapy with nivolumab alone. So, in the study, as you alluded, the dose and schedule of the two drugs used was nivolumab at 3 milligrams per kilogram, and ipilimumab with 1 milligram per kilogram. That was based on a series of signal finding and safety studies that had been previously done by the same group of authors identifying that as the optimal treatment regimen. And it's worth noting that's slightly different than the labeled indication that's generally used for those same drugs for metastatic melanoma, albeit that the NCCN also endorses this schedule. So, in the trial, 423 patients were randomized, 1:1 to receive either neoadjuvant therapy with those 2 doses of nivolumab plus ipilimumab as compared with standard adjuvant therapy with nivolumab following surgery. Now, one interesting tweak was that there was an adaptive nature to the study, meaning that patients had a fiducial placed at the index lymph node, and after the neoadjuvant therapy in that arm, that lymph node was removed. And if the patient had a major pathological response, they did not go on to receive the adjuvant portion of the treatment. So it was adaptive because those patients who did very well to the neoadjuvant did not require the adjuvant portion. And in those patients who did not achieve a major pathological response, they could go on to have the adjuvant therapy. And that also included the BRAF therapy for those whose tumors were BRAF mutants. It's also worth pointing out that the definition of event free survival was slightly different than in the S1801 study that was alluded to just a second ago. And here, EFS was defined from the date of randomization until progression due to melanoma or due to treatment. So that's slightly different than the definition in the S1801 trial. So, a somewhat complicated study, but I really applaud the authors because I think this study does mirror what we would likely be doing in actual clinical practice. Dr. Diwakar Davar: So, just to briefly summarize the efficacy, and then to get your comments on this, the path response, the PCR rate was 47%. The major pathologic response rate, which is the proportion of patients with between 0% to 1/10% of residual viable tumors, was about 12%. And for a major pathologic response rate of 0% to 10% of 59%. And then the rest of the patients had either pathologic partial response, which was 10% to 50%, or pathologic non response or 50% or greater residual viable tumor, all assessed using central pathology grades. The one year RFS was 95% in the FDR patient population versus 76% in the pathologic partial response patient population, 57% in the pathologic non response patient population. So how do you view these results? Can you context the FDR rates and the EFS rates from NADINA relative to nivo-rela and also potentially SWOG 1801? Dr. Jason Luke: Well, I think these are very exciting results. I think that for those of us that have been following the field closely, they're actually not especially surprising because they mirror several studies that have come before them. When we put them in context with other studies, we see that these rates of major pathological response are consistent with what we've seen in phase 2 studies. They're relatively similar. Or I should say that the results from nivolumab and relatlimab, which was also pursued in a phase 2 study of somewhat similar design, are somewhat similar to this. So, combination immunotherapy does look to deliver a higher major pathological response than pembrolizumab alone, as was known in S1801. Which of course, the caveat being is these are cross control comparisons that we need to be careful about. So I think all of these are active regimens, and I think adding a second agent does appear to enhance the major pathologic response rates. When we look at the event free survival, we see something similar, which is that numerically it looks to be that combination immunotherapy delivers a higher event free survival rate. And that looks to be rather meaningful given the difference in the hazard ratios that were observed between these various studies. And here in the NADINA study, we see that 0.3 hazard ratio for EFS is just extremely impressive. So the abstract then, from ourselves, out of these specific studies, what does this mean more broadly in the real world, where patients exist and the rest of the landscape for clinical trials? I think we can't take enough time to stop for a second and just think about what a revolution we've come forward in with immune checkpoint blockade and melanoma. When I started my career, now, more than 15 years ago, melanoma was the cancer that made cancer bad. And now here we say, in the highest risk of perioperative patients, we can deliver 2 doses of nivolumab and ipilimumab, and essentially half of the patients then don't need to go on, and more than half the patients don't need to go on to have a full surgery and don't need adjuvant therapy. And from what we could tell of a very, very low risk of every heavy recurrence of melanoma. Of course, there's the other half of patients where we still need to do better, but these are just fantastic results and I think highly meaningful for patients. In the context of ongoing clinical trials, another abstract that was presented during the meeting was the update to the individualized neoantigen therapy, or V940 with pembrolizumab or against pembrolizumab alone. That's the KEYNOTE-942 study. In that study, they presented updated data at two and a half years for relapse free survival, noting a 75% rate without relapse. So those results are also highly intriguing. And these are in a similar population of very high risk patients. And so I think most of us believe that neoadjuvant therapy with this study in NADINA is now confirmed as the priority approach for patients who present with high-risk stage 3 disease. So that would be bulky disease picked up on a scan or palpable in a clinic. I think essentially all of us now believe patients should get preoperative immunotherapy. We can debate which approach to take, and it may vary by an individual patient's ability to tolerate toxicity, because, of course, multi agent immunotherapy does have increased toxicity relative to anti PD-1 alone. But we'll have to wait now for the full phase 3 results from the V940 individualized neoantigen therapy. And if those come forward, that will be an extremely attractive approach to think about for patients who did not achieve a major pathological response to neoadjuvant therapy, as well as of course to the other populations of patients with melanoma where we otherwise currently give adjuvant therapy stage 2B all the way through stage 4 resected. It's an amazing time to think about perioperative therapy in melanoma. Dr. Diwakar Davar: So this is clearly outstanding data, outstanding news. Congratulations to the investigators for really doing what is an investigative initiated trial conducted across multiple continents with a huge sample size. So this clearly appears to be, at this point in time at least, a de facto standard. But is this going to be FDA-approved, guideline-approved, or is it possible in your mind? Dr. Jason Luke: Well, that's an interesting question. This study was not designed with the intent to necessarily try to register this treatment regimen with the FDA. One would have to take a step back and say, with how powerful these data appear, it sort of seemed like it would be too bad if that doesn't happen. But all the same, I think the community and those of us who participate in guideline recommendations are fully supportive of this. So, I think we will see this move into compendium listings that support insurance approval, I think, very, very quickly. So, whether or not this actually becomes formally FDA approved or is in the guidelines, I think this should become the standard approach that is considered for patients, again presenting with high-risk stage 3 disease. Dr. Diwakar Davar: Fantastic. So now we're going to go in and talk about a slightly different drug, but also from the melanoma context, and that is the safety and efficacy of RP1 with nivolumab in the context of patients with melanoma who are PD-1 failures. So, this is Abstract 9517. And in this abstract, our academic colleagues essentially talked about these data, and we'll start by describing what RP1 is. RP1 essentially is a HSV-1 based oncolytic immunotherapy. And RP1 expresses GM-CSF as well as a fusogenic protein, GALV-GP-R-. And in this abstract, Dr. Michael Wong from MD Anderson and colleagues are reporting the results of IGNYTE, which is a phase I trial of intratumoral RP1 co-administered with systemic nivolumab in patients with advanced metastatic treatment refractory cutaneous melanoma. And the data presented in this abstract represents data from a registration directed, abbreviated as RD, registration directed cohort of RP1 plus nivolumab in PD-1 refractory melanoma. So, let's start with the description of the cohort. Dr. Jason Luke: Right. So, in this study, there were a total of 156 patients who were presented, and that included an initial safety and dose finding group of 16, as well as the RD cohort, as you noted, of 140 patients. And it's important to point out that this was a cohort that was selected for a very strict definition of progression on anti PD-1, or a combination immunotherapy as their immediately prior treatment. So, all of the patients in the cohort had exposure to anti PD-1, and 46% of them had anti PD-1 plus anti CTLA4, nivolumab and ipilimumab as their immediately prior therapy. This was also a group of relatively high-risk patients when one considers stage. So, within the stage 4 population, the entry here included 51% who had stage M1B, C, and D melanoma. And that is worth pointing out because this is an injectable therapy. So, trials like this in the past have tended to be biased towards earlier stage, unresectable or metastatic melanoma, meaning stage 3B, 3C, 3D and then stage 4m1a. Again, to emphasize the point here, these were pretreated patients who had a strict definition of anti PD-1 resistance, and over half of them, in fact, had high-risk visceral metastatic disease. In that context, it's very interesting to observe that the overall response rate was described in the total population, as 31%, and that included 12% who achieved complete response. And so, again, to make sure it's clear, we're talking about a treatment where the oncolytic virus is injected into one or multiple sites of recurrent disease, and then the patients administer nivolumab as per standard. And so, I think these data are quite intriguing. Again, such a high- risk population and their maturity now, with a follow-up of over a year, I think, makes this look to be a very interesting treatment option. Dr. Diwakar Davar: I guess on that topic of mature follow-up, it probably would be important for us to inform our audience that the top line data for the primary analysis was actually just released, I think, earlier today, and wherein the central confirmed objective response rate was 34% by modified RECIST and 33% by RECIST, clearly indicating that these responses, as you noted, very treatment refractory patient population, these responses were clearly very durable. So, you mentioned that there were responses seen in uninjected visceral lesions, responses seen in both PD-1 and PD-1 CTLA-4 refractory patients. Can you talk a little bit about the response rate in these high-risk subgroups, the uninjected visceral lesions, the patients who had both combination checkpoint and epidural refractory response rate by primary PD-1 resistance. Dr. Jason Luke: Sure. You know, I think, again, to emphasize this point in the study, we saw that there were responses in the non-injected lesions, and I think it's really important to emphasize that. Some have referred to this as a putative abscopal like effect, similar to what is described in radiation. But it implies that local treatment with the oncolytic virus is triggering a systemic immune response. In the higher risk patient population, we'll note that whereas the overall response rate in PD-1 refractory patients was 34%, in the combination of PD-1 and CTLA-4 refractory patients, the response rate was 26%. So, [this is] still very good. And when we looked at that split by stage, as I alluded to before, in the population of patients that had, what you might call earlier unresectable diseases, so 3B through 4A, the response rate was 38%, and in the stage 4 M1b through M1d, it was 25%. So slightly lower, but still very good. And that would be as expected, because, of course, the patients with visceral metastatic disease have more advanced disease, but those response rates look quite good. Again, looking at the combination refractory population as well as the more high-risk disease. Dr. Diwakar Davar: So, clearly, these are very promising data and exciting times for multiple investigators in the field and the company, Replimune, as well. So, what are the next steps? I believe that a registration trial is planned, essentially, looking at this with the goal of trying to get this combination registered. Can you tell us a little bit about IGNYTE-3, the trial design, the control arm, and what you foresee this trial doing over the next couple of years? Dr. Jason Luke: So, as this agent has been maturing, it's worth pointing out that the company that makes this molecule, called RP1, but I guess now we'll have to get used to this name vusolimogene oderparepvec as the actual scientific term, they have been having ongoing discussions with the FDA, and there is the potential that this agent could come forward on an accelerated path prior to the results being released from a phase 3 trial. That being said, the phase 3 confirmatory study, which is called the IGNYTE-3 study, is in the process of being launched now. And that's a study investigating this molecule in combination with nivolumab, as was alluded to earlier, and a randomized phase 3 design, where that combination is compared with a physician's choice, essentially a chemotherapy-based option. In that study, it will be 400 patients with stage 3B through stage 4; patients will have progressed on anti PD-1, either as a combination or in sequence, and then come on the study to be randomized to either vusolimogene oderparepvec plus nivolumab versus that physician's choice. And the physician's choice includes chemotherapy agents, but also nivolumab plus relatlimab as another option, or an anti PD-1 monotherapy, if that's deemed to be a reasonable option by the treating investigator. And the primary endpoint of that study is overall survival. And unfortunately, in this highly refractory patient population, that's something that may not take long to identify with key secondary endpoints of progression free survival, as well as overall response rate. I'm quite enthusiastic about this study, given these data, which have now been centrally confirmed as you alluded to before. I think this is a very exciting area of investigation and really crossing my fingers that this may be perhaps the first locally administered therapy which does appear to have a systemic impact that can hold up in phase 3. Dr. Diwakar Davar: Very, very, very exciting results. And I guess it's worthwhile pointing out that this company also has got, I think, multiple studies planned with both RP1 and cutaneous squamous cell carcinoma in a solid organ transplant patient population where single agent activity has already been reported by Dr. Migden at prior meetings, as well as a novel trial of potentially RP2 metastatic uveal melanoma. So we'll now pivot to Abstract 6014. So, 6014 is a drug by a company known as Merus. Essentially, it's a very novel agent. Merus essentially is a company that is specialized in making bicyclics and tricyclics. And these are not bicycles or tricycles, but rather drugs that essentially are bispecific antibodies. And Merus essentially has come up with petosemtamab. I think we're going to have to figure out better names for all of these drugs at some point. But petosemtamab, or MCLA-158, essentially is a bicyclic, targeting both EGFR as well as LGR-5. So EGR-5, of course, is a known oncogenic driver in multiple tumor types, squamous, including non small cell lung cancer, cutaneous squamous cell carcinoma, but also head and neck squamous cell carcinoma. And LGR-5 essentially is leucine-rich repeat-containing G-protein coupled receptor 5, but it's a receptor in cancer stem cells and certainly highly expressed in head neck squam. And MCLA-158, or petosemtamab is a IgG one bispecific with ADCC-activity because of IgG1 backbone co-targeting EGFR and LGR5. Merus had earlier results that evaluated petosemtamab monotherapy. They defined the RP2D and second- and third-line head and neck blastoma patients with a respectable response rate of 37% investigator-assessed ORR with six months median DoR, and this was published by Ezra Cohen about a year or so ago. In this abstract, Dr. Fayette and colleagues report on the results of the MCLA-158-CL01 trial, which is a trial of pembrolizumab plus petosemtamab in one front line head and neck squamous cell population. So maybe let's start with the description of the cohort. And it is a small trial, but we'll be able, I think, to dig into a little bit about why this might be exciting. Dr. Jason Luke: Yes. So, as alluded to, it's not the biggest trial as yet, but there were 26 patients with anti PD-1 treatment naive head and neck squamous cell carcinoma. And all the patients in the study did receive, as you alluded to, pembrolizumab plus petosemtamab. Based on the label for pembrolizumab, all the patients in this study were PDL-1 positive. So that's one point that it's worth pointing out to make sure that that's understood. This is the population of patients who would be expected to benefit from pembrolizumab in the first place. Now, in the abstract, they reported out only 10 response evaluable patients, but they updated that in the actual slides of presentation at the meeting. So among 24 patients that were alluded to, 67% were described as having had a response, although some of those were yet to be confirmed responses. And when it was evaluated by PDL-1 status, there didn't seem to be a clear enrichment of response in the PD-1 positive more than 20% group, as compared to the 1-19% group. That isn't especially surprising because that was a trend that one would see, presumably with pembrolizumab alone. But overall, I think these data are pretty exciting in terms of a preliminary study. Dr. Diwakar Davar: You know, you mentioned that the objective response rate was high, almost 60-something%. The prognosis of these patients is generally poor. The OS is typically thought of as between 6-15 months. And based on KEYNOTE-048, which was led by Dr. Burtness and colleagues, the standard of care in the setting is pembrolizumab +/- platinum based chemotherapy regimens. Allowing for the fact that we only have 10 patients here, how do you think these results stack up against KEYNOTE-048? And you made a very important point earlier, which was, by definition, pembro is on label only for the CPS. So PDL-1 score, at least in head and neck squamous cell carcinoma CPS and not TPS. But in the CPS 1% or greater patient population, where pembro is on label, how do these results stack up against the KEYNOTE-048 results. Dr. Jason Luke: Right. KEYNOTE-048 is considered the seminal study that dictates frontline treatment in head and neck cancer. And before we dive into this too far, we do want to acknowledge that here we're comparing 26 patients versus a phase 3 trial. So, we're not trying to get too far ahead of ourselves, but this is just a preliminary comparison. But in KEYNOTE-048, as you alluded to, two regimens were superior to chemotherapy. One was the pembrolizumab monotherapy, as well as pembrolizumab plus chemotherapy. So again, the study overall survival, of course, was much higher, the PDL-1 positive subgroup, which is what dictated the unlabeled use of this. But response to pembro monotherapy in that population of patients is still modest. We're talking about upwards of 20-30%. So, if you compare that to, again, preliminary evidence here from this trial of only 24 patients, that response rate of 60% seems extremely high. And so even if that were to come down somewhat in a larger data series of patients, that still looks to be quite promising as a treatment regimen, that might eventually even be chemotherapy sparing for this population of patients. I think this raises a lot of eyebrows that perhaps this dual targeting approach, EGFR and LDR-5, may bring something really important to the field that evolves it. Dr. Diwakar Davar: So, what are the next steps for petosemtamab? You mentioned that the activity was interesting. Are we going to see a larger trial? Any thoughts on where things are going to go? Dr. Jason Luke: Well, based on the phase 2 data of petosemtamab alone, even without pembrolizumab, the molecule had already been given fast track designation by FDA, which means allowing for greater communication between the drug sponsor in the FDA and designing a seminal study design. One would assume that this trial will be rapidly expanded quite greatly, perhaps to 100 or 200 patients, to try to flush out what the real response rate is in a more meaningful number of patients. But I think these data will probably also trigger the design and probably near-term evaluation or expedited acceleration of a phase III clinical trial design that would potentially validate this against the current standard of care. So, I'm pretty excited. I think we'll see a lot more about this agent in the relatively near future. Dr. Diwakar Davar: So, finally, we'll pivot to the last abstract that we're going to talk about, which is Abstract 2504. It's a relatively interesting target, CCR8 monoclonal antibody. But this is the efficacy and safety of LM-108, and LM-108 is an anti CCR8 monoclonal antibody that is being developed by LaNova Medicine. And the results that are described, actually a pool set of results of combinations of LM-108 with anti PD-1, two separate anti PD-1, in patients with gastric cancer, mostly done ex-U.S., which is interesting because of this patient population, and it's a pool result of several, 3 phase 1 and 2 studies. LM-108 is an Fc-optimized anti CCR8 monoclonal antibody that selectively depletes tumor infiltrating Tregs. The abstract reported a pooled analysis of three phase 1, 2 trials with 3 different NCT numbers that all evaluated the efficacy of LM-108 and anti PD-1 in patients with gastric cancer. So, let's start with the description of the cohort. Maybe, Jason, you can tell us a little bit about before you start, as you describe the cohort, sort of what we know, editorially speaking, about the difficulty with which Tregs depletion has been tried and obviously failed up until now in the tumor microenvironment. Dr. Jason Luke: Right. I think that's a really interesting comment. And so, for decades, in fact, targeting regulatory T-cell to alleviate immune exclusion in the tumor microenvironment has been of interest in immuno-oncology. And in preclinical mouse models, it seems quite clear that such an approach can deliver therapeutic efficacy. However, by contrast, in human clinical trials, various different Treg depleting strategies have been attempted, and there's really little to no evidence that depleting Tregs from human tumors actually can deliver therapeutic responses. And by that we're referring to CD-25 antibodies. The drug ipilimumab, the CTLA-4 antibody, was punitively described as a Tregs depleter preclinically, but that doesn't seem to be the case in patients. And so, in that background, this is quite an eye raiser that an anti CCR8 antibody could be driving this effect. Now, before we talk about the results of this trial, I will point out, however, that given the Fc-optimization, it's entirely possible that the Tregs are being depleted by this mechanism, but that more could also be going on. Because Fc gamma RII binding by this antibody that could be nonspecific also has the potential to trigger immune responses in the tumor microenvironment, probably mediated by myeloid cells. So I think more to come on this. If this turns out to be the first meaningful Tregs depletor that leads to therapeutic efficacy, that would be very interesting. But it's also possible this drug could have multiple mechanisms. So, having said all of that, in the clinical trial, which was a pooled analysis, like you mentioned, of LM-108 in combination with anti PD-1 of a couple different flavors, there were 48 patients treated either with LM-108, with pembrolizumab, or with toripalimab, which is another anti PD-1 antibody. On the drug combination was, generally speaking, pretty well tolerated, noting grade 3 treatment related adverse events in the range of 38%, which is somewhat expected given combination immunotherapy. We talked about nivolumab and ipilimumab before, which, of course, gives even higher rates of immune-related adverse events, with the most common toxicities being anemia, lipase elevations, rash, ALC decrease; albeit, quite manageable. Dr. Diwakar Davar: So, what about the objective response rate? Can you contextualize the efficacy? And as you do that, maybe we'll think about what you'd expect in the context of, say, gastric cancer, especially in patients who've never really had a prior checkpoint inhibitor before. What do you think about the ORR? What do you think about the relative efficacy of this combination? Dr. Jason Luke: Well, so, in the study, they described overall response rate in the 36 patients as 36% and described immediate progression for survival of about 6.5 months. And so that was among patients who were treatment naive. And in second-line patients, they actually described an even higher response rate, although it was only 11 patients, but they're at 64%. And so, I think those data look to be somewhat interesting. When I was actually scrutinizing the actual data presented, it was of some interest to note that the quality of responses seemed to be about as good on the lower dose of LM-108, so 3 milligrams per kilogram as compared to 10 milligrams per kilogram. I think there's definitely more to learn here to try to optimize the dose and to fully understand what the overall efficacy of this treatment combination would be. I would emphasize that in this disease, I think novel treatment strategies are certainly warranted. While anti PD-1 with chemotherapy has moved the needle in terms of standard of care treatment, it's really only a minor subset of patients who derive durable long-term benefit like we normally associate with immune checkpoint blockade. I think these are preliminary data. They're very intriguing. You alluded to earlier that this population of patients was an Asian data set, and it is well known that the efficacy of chemotherapy and immunotherapy does appear to be somewhat enhanced in Asian populations, and that goes to distributions of metastasis and tumor microenvironment effects, etc. Very difficult to try to tease any of that out in this abstract, other than to look at these data and suggest that this is pretty interesting, both from a novel therapeutic approach, we talked about the Tregs consideration, but also straight up on the efficacy because I think if these data could hold up in a larger number of patients, and particularly in a western population of patients, I think it would be very intriguing. Dr. Diwakar Davar: Certainly, ASCO 2024 had a lot of interesting data, including data from targeted agents, the LAURA trial, ADCs. But just focusing on the immune therapy subset, we certainly saw a lot of great advances in patients who were treated with neoadjuvant as well as relapse refractory disease in the context of RP1 and then a couple of newer agents such as this petosemtamab as well as LM-108. And of course, we cannot forget to highlight the extended DMFS data from the pembro vaccine study from KEYNOTE-942. Jason, as always, thank you for taking a little bit of time out of your extremely busy schedule to come and give us insights as to how these agents are impacting the landscape. We really value your input and so thank you very much. Dr. Jason Luke: Thank you for the opportunity. Dr. Diwakar Davar: And thank you to our listeners for your time today. You will find the links to all the abstracts that we discussed in the transcript of this episode. And finally, if you value the insights that you hear on this podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. So, thank you. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers: Dr. Diwakar Davar @diwakardavar Dr. Jason Luke @jasonlukemd Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Diwakar Davar: Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences Consulting or Advisory Role: Instil Bio, Vedanta Biosciences Consulting or Advisory Role (Immediate family member): Shionogi Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences Research Funding (Inst.): Zucero Therapeutics Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy Dr. Jason Luke: Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof) Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

university ai spring 3d asian os pittsburgh cd studies fda congratulations pfizer keynote patel werewolf relation franklin delano roosevelt pd immune bayer pcr abstract oncology merck 2b endeavor cps 3b janssen new england journal novartis melanoma dor alc royalties lag hsv accommodations immunotherapy cancer care gsk tps asco 4a lm genentech ldr 3c orr abbvie stipe bristol myers squibb nct takeda igg regeneron adcc egfr gilead sciences adverse events md anderson rfs nektar pdl onc efs adcs prognostic cancer immunotherapy braf esmo plenary session neoadjuvant eisai immuno oncology asco annual meeting treg pyxis nadina nccn rubius servier michael wong ctla rp1 emd serono incyte ezra cohen lgr alnylam genmab mcla moderna therapeutics gm csf tregs swog ignyte ctla4 rp2 tesaro jason luke recist transcript dr array biopharma igg1 synlogic

ASCO24: The Future of Personalized Immunotherapy

Play Episode Listen Later May 24, 2024 34:42

Dr. Diwakar Davar and Dr. Jason Luke discuss key abstracts from the 2024 ASCO Annual Meeting that explore triplet therapy in advanced melanoma, TIL cell therapy in immune checkpoint inhibitor–naive patients, and other novel approaches that could shape the future of immunotherapy in melanoma and beyond. TRANSCRIPT Dr. Diwakar Davar: Hello and welcome to the ASCO Daily News Podcast. I am your guest host, Dr. Diwakar Davar. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. I'm delighted to have my friend and colleague, Dr. Jason Luke, on the podcast today to discuss key abstracts in melanoma and immunotherapy that will be featured and highlighted at the 2024 ASCO Annual Meeting. Dr. Luke is an associate professor of medicine, the director of the Cancer Immunotherapeutic Center, as well as the associate director for clinical research at the University of Pittsburgh's Hillman Cancer Center. You will find our full disclosures in the transcript of this episode. Jason, as always, it's a pleasure to have you on this podcast to hear your key insights on trials in the immunotherapy space and melanoma development paradigm, and to have you back on this podcast to highlight some of this work. Dr. Jason Luke: Thanks so much for the opportunity to participate. I always enjoy this heading into ASCO. Dr. Diwakar Davar: We're going to go ahead and talk about three abstracts in the melanoma space, and we will be starting with Abstract 9504. Abstract 9504 essentially is the RELATIVITY-048 study. It describes the efficacy and safety of the triplet nivolumab, relatlimab, and ipilimumab regimen in advanced PD-1 naive melanoma. So in this abstract highlighted by Dr. Ascierto and colleagues, they report on the results of this phase 2 trial in this setting. By way of background, PD-1 inhibitors and immune checkpoint inhibitors starting in PD-1 and CTLA-4, as well as PD-1 and LAG-3, are all FDA-approved on the basis of several pivotal phase 3 trials, including KEYNOTE-006, CheckMate-066, CheckMate-067, and most recently, RELATIVITY-047. Jason, can you briefly summarize for this audience what we know about each of these drugs, at least the two combinations that we have at this time? Dr. Jason Luke: For sure. And of course, these anti PD-1 agents, became a backbone in oncology and in melanoma dating back to more than 10 years ago now, that response rates in the treatment-naive setting to anti PD-1 with either pembrolizumab or nivolumab are roughly in the range of mid-30s to high-40s. And we've seen clinical trials adding on second agents. You alluded to them with the seminal study being CheckMate-067, where we combined a PD-1 antibody and CTLA-4 antibody or nivo + ipi. And there the response rate was increased to approximately 56%. And more recently, we have data combining PD-1 inhibitors with anti-LAG-3. So that's nivolumab and relatlimab. Now, in that trial, RELATIVITY-047, the overall response rate was described as 43%. And so that sounds, on a first pass, like a lower number, of course, than what we heard for nivolumab and ipilimumab. We have to be cautious, however, that the cross-trial comparison between those studies is somewhat fraught due to different patient populations and different study design. So I think most of us think that the response rate or the long-term outcomes between PD-1, CTLA-4, and PD-1 LAG-3 are probably roughly similar, albeit that, of course, we have much better or much longer follow up for the nivo + ipi combo. The one other caveat to this, of course then, is that the side effect profile of these two combinations is distinct, where the incidence of high-grade immune-related adverse events is going to be roughly half with nivolumab and relatlimab, a combination of what you would see with the nivolumab and ipilimumab. So that has caused a lot of us to try to think about where we would use these different combinations. But we do see that all of these treatments can land a durable long-term response in the subset of patients that do have an initial treatment benefit. The landmark, I think, for the field has been the 7-and-a-half-year median overall survival that we've seen with PD-1 plus CTLA-4, nivo + ipi; of course, we don't have such long-term follow up for PD-1 and LAG-3. But I think that's the setting for thinking about the rationale for combining a triplet regimen of PD-1, CTLA-4, and LAG-3. Dr. Diwakar Davar: So, Jason, in your mind, given the difference in the disparity and durability of the responses for the 067 regimen of nivo-ipi, and the RELATIVITY-047 regiment of nivo-rela, what is the standard of care in the U.S., and how does it change in the rest of the world, knowing that nivo-rela is not necessarily approved in all jurisdictions? Dr. Jason Luke: So this is a major complication in our field, is that there is perhaps not complete agreement across the world in terms of what the frontline standard of care should be. I think most United States investigators, or those of us that really treat melanoma most of the time, would suggest that a combination regimen, given the enhanced response rate and longer-term outcomes, should be the consideration for the majority of patients. In fact, in my practice, it's hard to think of who I would treat with a monotherapy PD-1 approach in the PD-1 naive setting. So either nivo + ipi or nivo + rela. As you alluded to however, in other regulatory settings throughout the world, combinations might not actually even be approved at this point. So PD-1 monotherapy would be the backbone of that setting. It does set up some complications when you think about a comparator arm; say you were going to look at various combinations, probably PD-1 monotherapy would be the worldwide comparator. You have to understand though, in the United States, I think that that's a less attractive option. Dr. Diwakar Davar: So in RELATIVITY-047, Dr. Ascierto and his colleagues are looking at generating a triplet. And in this case, they looked at this in the context of frontline metastatic melanoma, 46 patients. Very interestingly, the dose of ipilimumab studied here was 1 mg/kg through 8 weeks, not the 3 mg/kg every three weeks times four doses using 067, or even the low dose ipilimumab regimen that you studied in the second line setting, which was 1 mg/kg every 3 weeks for 4 doses. So let's talk about the results and specifically the implications of potentially studying lower doses of ipi. Dr. Jason Luke: I appreciate you raising that point. I think it's really important as we think about this dataset because this triplet regimen is not by any means the only version of a triplet that could be developed using these agents. So just to give the high-level numbers from the abstract, we see from these data that the overall response rate is described as 59% and 78%, a disease control rate with patients having an unreached link. So duration of response of unreached, and then the progression-free survival at about 5 months. So those are really interesting data. But as was alluded to, it's not totally clear to me that that's the best that we could do with this regimen. Now, you alluded to this low-dose ipilimumab schedule at 1 mg/kg every 8 weeks, and it's really important to note that we have no benchmark for that regimen in melanoma oncology. And in fact, the one study that used that regimen, which was the adjuvant study of nivolumab and ipilimumab, known as CheckMate915, is in fact the only immune checkpoint inhibitor study in melanoma oncology that was actually negative. That study noted no benefit to adding ipilimumab at 1 mg/kg every 8 weeks on top of nivolumab, again, the adjuvant setting. So it's a little bit curious to then understand what it means in this study to have that amount of ipilimumab added to the rela-nivo backbone. And that manifests in a few different ways. We see the response rate here at 59%. Again, if you compare that just against the standard nivo + ipi dosing schedule, it's about the same. So is that really an advantage to having the triplet as compared to just doing standard nivo + ipi? We do see that it manifests in a slightly lower rate of grade 3/4 immune-related adverse events, at 39%. That's a little bit lower than what we'd expect for standard nivo + ipi. But again, I think that that emphasizes to me the possibility that some efficacy was left on the table by using this very low dose ipilimumab regimen. I think that's really a concern. It's not clear to me that these triplet data really differentiate from what we'd expect with the already approved regimen of nivo + ipi. Therefore, it makes it difficult to think about how would we really want to move this regimen forward, or should there be more work done about dose and schedule to optimize how we might want to do this? Dr. Diwakar Davar: As far as triplet therapy in the context of frontline metastatic melanoma, meaning triplet immune therapy, because there are at least several targeted therapy triplets that are FDA-approved, [but] not necessarily widely utilized. How would you summarize the future for triplet therapy? Do you think it's potentially attractive? Do you think it's very attractive with some caveats? Dr. Jason Luke: Well, I think it's attractive, and we have 3 independently active agents. And so I do think it's a priority for the field to try to figure out how we could optimize the therapy. We've had such a revolution in melanoma oncology, talking about 7.5-year median survival from CheckMate-067, but that still implies that 7.5 years, half the patients have passed away. There's more to do here. And so I do think it should be a priority to sort this out. I guess I would be cautious, though, about advancing this regimen directly to a phase 3 trial because it doesn't seem clear to me that this is optimized in terms of what the outcome could be. If we're willing to tolerate higher rates of toxicity from other dose schedules of nivo-ipi alone, then I think we should do a little bit more here to potentially explore the space that might be possible to increase that overall response rate a little more without getting into a completely exaggerated toxicity profile that would be unacceptable. So, I do think it's exciting, but there's possibly more to do before really think about going big time with this. Dr. Diwakar Davar: Great. So now we'll switch gears and move from frontline metastatic melanoma to the second line and beyond looking at a new agent and contextualizing the effects of that actually in the frontline settings. So Abstract 9505 describes the efficacy and safety of lifileucel, which is essentially autologous tumor-infiltrating lymphocyte cell therapies, also known as TIL, in combination with pembrolizumab in patients with ICI naive, so not necessarily pretreated, but ICI naive metastatic or unresectable melanoma. This is data from the IOV-COM-202 Cohort 1A oral abstract presented by Dr. Thomas and colleagues. In this abstract, Dr. Thomas and colleagues are presenting data from the 1A cohort, which is the phase 2 portion of the frontline trial that is evaluating autologous TIL with pembro in checkpoint inhibited naive metastatic melanoma. By way of background, TIL is FDA approved on the basis of several cohorts from a phase 2 trial. The data has been presented multiple times now by Drs. Sarli, Chesney, and multiple colleagues of ours. And essentially autologous TIL, which is generated from a surgical procedure in which a patient undergoes a surgery to extract a tumor from which T cells are then grown after ex vivo expansion and rapid expansion protocol. The entire procedure was essentially pioneered by several colleagues at the NCI, primarily Dr. Steve Rosenberg, and this approach produces objective response rates of approximately 31% to 36%. And the most recent publication demonstrated that at median follow up of approximately 2 years, the median duration of response was not reached. The median OS was about 14 months and PFS was about 4 months or so. So, can you contextualize the results of the abstract in the frontline setting? And then we'll talk a little bit about where we think this is going to go. Dr. Jason Luke: So I think this is a timely study given the recent approval. And in the abstract presented here, we see an early data cut from the PD-1 naive study, as you alluded to. So here we had 22 patients and distributed across various states of advanced melanoma. Ten out of the 22 had M1C, but there also were smatterings of earlier M1A and M1B at 18.2% and 9.1%. So this is important, as we think who the treatment population is that's going to be optimized with a TIL procedure. The median sum of diameters, meaning how much tumor burden the patients have, was about 5.5cm, and I'll note that that's a relatively modest amount of tumor burden, albeit not that unusual for an early-stage trial. So of the patients that participated, 8 had BRAF mutations so that's 36%. That's not that high, but it's reasonable. And I think the important overlying number, the response rate so far in the study, with about 17 months of follow up, was 63.6%, and that includes 22% or 23% having complete response. So those are interesting data. And another point that was made in the abstract, which we've all seen, is that responses to TIL, all of immunotherapy but especially TIL, do seem to mature over time, meaning they deepen over time. So it's possible the response rate could go up some extent as we watch this study advance. So I think these are exciting data on some level. Also, a 63.6% response rate sounds pretty impressive, but we do have to put that in the context of a double checkpoint blockade, which we just got done discussing, gives you almost a 60% response rate, 59% response rate. So then the question really is: Is it worth the amount of effort that we could go into generating a TIL product in a treatment naive patient, and put them through the lymphodepletion that is associated with TIL and the high dose interleukin 2 treatment that accompanies the reinfusion of the TIL, if you're going to get a response rate that's roughly the same as what you would get if you gave them off the shelf nivo plus ipilimumab? At this point it's a little bit hard to know the answer to that question. I think it could be possible that the answer is yes, because we don't know exactly which populations or patients are most likely to benefit from each of these therapies. And if it could be teased out who's not going to benefit to nivo + ipi from the get-go, then of course, we would want to offer them a therapy that has that frontline potential, durable, long-term response. But I have to say, on a one-to-one with TIL therapy, you get a lot of toxicity initially with the treatment; with nivo + ipi on the back end, you get a fair amount of toxicity with the treatment. How are we going to judge those two things? And I think we probably need a larger dataset to really have a good handle on that. So these are interesting early data, but it's not totally clear to me that even if this holds up all the way through the trial, and we're going to talk about the design of the registration trial here in a second, a 60% response rate on its own without further biomarker stratification is a little bit hard for me to see in clinical practice why we would want to do that, given we can already just go off the shelf and give checkpoint inhibitors. Dr. Diwakar Davar: So that brings us to TILVANCE-301. So TILVANCE is a phase 3 trial. It's a registration intent trial by our Iovance colleagues evaluating the pembro-TIL regimen versus pembrolizumab alone. So in this phase 3 trial, approximately 670 patients will be randomized to either arm A, which is lifileucel + pembro. And in this arm A, patients are going to be getting lifileucel with the tumor resection, non-myeloablative lymphoid depletion, the lifileucel and abbreviated course of high-dose IL-2, and thereafter, continued pembro for the study mandated duration versus arm B, where patients will be getting just pembrolizumab monotherapy per label. Arm B patients, per the design, may cross over to receive TIL monotherapy at the time of central-blinded, radiology-confirmed disease progression. The study design otherwise is fairly routine and, per most of our registration trials these days, patients have actually been permitted to receive neoadjuvant and adjuvant therapy, including checkpoint inhibitors, as long as the receipt of the therapy was more than 6 months prior to the inclusion of the patient in that registration trial. The dual primary efficacy endpoints as stated are BICR-assessed objective response rate as well as PFS, and the key secondary endpoint is overall survival. So Jason, what are your thoughts on the study design and potentially the regulatory implications, particularly given, one, the control arm of pembro monotherapy, and two, the role of TIL crossover to receive TIL monotherapy at the time of BICR mandated progression for arm B? Dr. Jason Luke: So this goes to a few points that we've touched on already in the discussion here. When we think about the primary endpoints for this study, with one of them being overall response rate, one has to assume that that's a given that they would get that. I feel like that's a low bar. And we go back to that cross-trial comparison. If their results end up being that the response rates are about 60%, I don't know that that differentiates necessarily from what's already available in the field with combination immune checkpoint blockade. For the purposes of the study that would mean it's a positive study, so I think that would probably be good. But again, the comparator to pembrolizumab monotherapy, I think some of us would argue, isn't really consistent with what we would do with a patient in our clinic. So it's not that it's bad per se, but I think there's going to be a whole lot of cross-trial comparison. So if the study is positive, that would be good for getting the drug available. It's still a bit hard though, based on the preliminary data that I've seen, to imagine how this would have uptake in terms of utilization as a frontline therapy. You alluded to the crossover, and I think there, the assumption is that patients who get TIL therapy as a second line perhaps would have an attenuated benefit. But I'm not sure that's really true. It certainly looks from the data that we have, like the patients who benefit most from TIL are going to be those who didn't respond to anti PD-1 in the front line. So I'm not sure how much difference there's going to be between first- and second-line TIL therapy, but those data will kind of wait to be seen. So I think it's an important study. Of course, the accelerated approval of TIL as a later line therapy is dependent on this trial being positive. So there is some risk that if this trial ended up not being positive, that that could have regulatory implications on the utility or availability of TILs, a subsequent line therapy. But all of these, I guess we'll have to wait to see the results. We do hope for a positive trial here, although I think it'll be nuanced to sort of interpret those data given that pembrolizumab monotherapy control arm. Dr. Diwakar Davar: Fantastic. So we've learned a lot about TIL, both its use in the second-line setting and this very exciting but potentially risky frontline trial that is ongoing at some centers in the United States and certainly a lot of ex-U.S. enrollment. So we'll now pivot to a related product which actually belongs to a much larger class of agents that are antigen specific T-cell therapies in a variety of different formats. And that is Abstract 9507, which is the “Phase 1 safety and efficacy of IMC-F106C, a PRAME × CD3 ImmTAC bispecific, in post-checkpoint cutaneous melanoma (CM).” Now, in this abstract, Dr. Omid Hamid and colleagues reported the results of this phase 1 trial. As a disclosure, I'm an investigator and the last author on this manuscript. Jason, it would be important for our audience, for us to maybe firstly, outline the PRAME as a target, and then the ImmTAC as a platform prior to discussing these results. So let's start with the target PRAME, which I think is a target that you know well. So why don't you start with the target and we'll talk a little bit about that and then the platform? Dr. Jason Luke: Yeah, so I think for the audience, being aware of PRAME, or the Preferentially Expressed Antigen in Melanoma, is going to be quite important moving into the future. So PRAME as a therapeutic target is a cancer testis antigen that's overexpressed in tumor tissues. And of course the name has melanoma in it, but it's not uniquely present in melanoma. So the expression patterns of PRAME as a target are very high in melanoma. So in cutaneous disease, this is upwards of almost 100%, somewhere between 95% and 100%, in metastatic melanoma tissues. And PRAME has several different roles on a molecular level, although I don't think for our purposes here, it's so much important to be aware of them, but rather that this is a very highly expressed target, which then can make it attractive for using T cell receptor-based therapies. And so in the case we're talking about here on the ImmTAC platform, that's a CD3 PRAME×CD3 bispecific approach. But of course there are other approaches that can also be taken, such as TCR T cells that directly go after PRAME itself. Dr. Diwakar Davar: Let's now talk about the platform and how it differs from some of the other antigen targeting platforms that you have just alluded to. I think the Immtac platform is basically a fusion protein comprising engineered TCRs with a CD3 specific short chain variable fragment. And then the engineered TCR therefore binds antigens in an HLA dependent fashion. But you know quite a lot about some of these alternative platforms, and I think it'll be important to contextualize for the audience the difference between ImmTAC, which is a prototype drug that is already approved in the context of tebentafusp. But how does this differ from some of the other more nuanced platforms, such as the Immatics TCR or TCR platform and TScan TCRT nanoplasmonic platform. Dr. Jason Luke: Right. So the ImmTAC platform as alluded to is already approved on the market with tebentafusp, which is the gp100-CD3 bispecific molecule. And the advantage of that approach is infusion off the shelf of a drug. The downside of it is that it is a weekly dosing strategy as it stands now. And there are some complicated disease kinetics associated with treatment response, which we'll come back to in the context of the PRAME bispecific. Those are, in contrast with T-cell receptor-transduced T cells, as an alternative strategy, which is a form of adopted cell transfer. So we just got done talking about TIL therapy, which of course, is trying to take lymphocytes out of the tumor and grow them up and then give them back. Here with TCR-transduced T cells, we're talking about taking leukopak from the blood and then using different transfection approaches to try to insert into the lymphocytes of the patient a T cell receptor that recognizes to a certain cancer antigen, in this case, PRAME. So you alluded to a couple of different companies that have different platforms to do this. Immatics has a molecule called IMA 203, for which there have been data disclosed in the past year, again showing some very interesting responses in patients who have highly refractory melanoma. That process, though, again, does require lymphodepletion before you reinfuse the cells. Again, in contrast, the ImmTAC, which is an off the shelf revenue administer, there you have to make the product and then bring the patient back, lymphodeplete, and give the cells back. Immatics platform uses a viral transfection vector. The T scan approach that you alluded to before uses an approach of a mixed system on multiple HLA backgrounds to try to get past HLA-A*02:01 only, and in this case, uses a plasmid-based transfection syndrome that perhaps can be more broadly utilized given the lack of a lentiviral vector. So this is a complicated area of technology that starts to get into immune engineering, and I think for the purposes of this discussion, we don't want to belabor it. But both of these technologies, talking about the CD3 bispecific with the off the shelf aspect of it and the adoptive cell transfer, each of these using a T cell receptor-based therapy to try to go after PRAME, I think have very high upsides, and I think we'll initially see it in melanoma over the next year or so. But this is likely to be relevant to multiple tumor types beyond melanoma. Dr. Diwakar Davar: So let's discuss the results of this phase 1 trial. IMC-F106C, like all other ImmTAC, is administered intravenously and does require step-up dosing. You alluded to the fact that the tebentafusp was approved, and it's one of those drugs that is fortunately otherwise administered weekly, which can be difficult for the patient and requires at least the patient spend the first 3 doses overnight under some kind of monitoring, whether it's in the hospital or extended outpatient monitoring, for at least 23 hours. The efficacy of this agent and this platform appears to be surprising in that you tend to see a relatively low RECIST response rate. We'll have you comment a little bit on why that is the case and what may be the role of ctDNA, as opposed to conventional RECIST in assessing response. At least in this trial, they mandated pre-testing, but did not require it for study enrollment. And pre-positivity was defined using immunohistochemistry with a relatively low H-score of 1%. And the molecular response definition was a 0.5 log or a 68% ctDNA reduction just prior to the first imaging assessment. So how do you contextualize the results? But maybe before you talk a little bit about the results, the ctDNA aspect, that was a recent publication by Drs. Rich Carvajal, Alex Shoushtari, and I think you are also involved in that. Dr. Jason Luke: So, I think an interesting observation around tebentafusp has been that ctDNA may be a better predictor of long-term outcomes. And how you define ctDNA response is still something that the field is grappling with, albeit that I think is going to be an important consideration as we think about these novel therapies, these ImmTACs and other CD3 engagers moving into the future. But for the purposes of the abstract here, we see that in the population of patients treated, there were 46 patients with cutaneous melanoma. The majority got monotherapy with IMC-F106C, and that's the PRAME bispecific. So 40 patients that got monotherapy and six who got a combination with checkpoint inhibitor. All these patients had prior treatment with immunotherapy, and most of them had PD-1 and CTLA-4 antibody with a small spanner that also had BRAF inhibitors. In terms of that PRAME testing that you alluded to, based on the immunohistochemistry H-score greater than 1%, 35 out of 40 patients were positive, so they defined 5 as negative. And we could come back if we have time, but there are other ways to do PRAME testing as well that I think may become unique for different agents, maybe an important biomarker. In the data, 31 out of the 46 patients were RECIST evaluable. The outcomes of those patients were to note that the response rate was 13%, which was four partial responses. But 35% of patients had tumor regression with a disease control rate at 65%. It was clear that there was an enrichment by PRAME positivity for both progression free and overall survival. So those patients who had obvious positivity essentially had a doubling of the PFS and more than the doubling of the OS, 2.1 to 4.1 months for TFS and landmark OS, 40% to 94%. So I think these are quite intriguing data. It does suggest that for the vast majority of patients, we do see some induction of the antitumor effect, albeit that RECIST might undercall the effect. And so this may become another area where the ctDNA monitoring might be able to help us to understand who is likely to have really long-term benefit from this therapy. And given the number of emerging treatments that we have for melanoma, we might be able to really focus in on that group of patients in terms of optimizing how we would use this drug moving into the future. Dr. Diwakar Davar: So you talked about a response rate, and at first glance, this response rate is a little underwhelming. We're talking about 4 out of 31 RECIST evaluable patients, 13%. So it's in the double digits, but barely. So how enthusiastic are you about the results? How does it contrast with at least the publicly known data from other brain targeting approaches, such as the IMA203 agent, understanding that while they may be all targeting somewhat the same target, they are actually extraordinarily different platforms. One's off the shelf, one's highly customized. How do you contextualize the results? How would it contrast with other cellular approaches? Dr. Jason Luke: I think it's important, again, to emphasize the point you made, which is that they're very different kinds of treatments. So even though they both target PRAME, they're going to be differently useful, and they could be quite useful for different groups of patients. And so here we see that there is a subfraction of patients who are deriving long-term benefit. And we commonly have an argument in our field about, is overall response rate really a useful monitor that describes a patient-centric outcome? While, of course, patients like to know their tumors are shrinking, what they want the most is for the tumors not to get worse and for them not to pass away from cancer. So I think I'm enthusiastic about these results, but emphasizing the point that we need to better understand who is going to benefit the most from this CD3 bispecific PRAME approach and how we're going to be able to harness that into long term benefit for patients because there's no doubt that an off the shelf therapy has a high degree of value relative to adoptive cell transfer, which sort of requires a big wind up. So when you say, what does it contrast with? Well, the data for IMA203 has shown more than a 50% response rate in patients with more than 5 lines of therapy for metastatic disease. That really looks quite exciting. And several of those patients are now out for quite an extended period, meaning 2 years or more given only a single dose of IMA203. But again, the caveat being, you have to make the cell product for the patient, and that takes time. You lymphodeplete the patient, not all patients can tolerate that in the refractory disease setting, and then they have to be able to tolerate the reinfusion of the cells. And so this drug, IMC-F106C, looks very promising. Moving into the earlier phase trial that we'll talk about, I think the TCR T cell program has a lot of upsides for patients, especially with refractory disease. And so I think these two different approaches are really on parallel tracks. They both target PRAME, but I don't think they necessarily need to be compared one to one, as if they're going to go head-to-head with each other. Dr. Diwakar Davar: So now we'll talk a little bit about the frontline setting, because on the basis of some of these results, Immunocore is now exploring IMC-F106C frontline melanoma. This trial is actually being presented as a trial in progress at this meeting by Georgina Long and colleagues. Some of us are co-authors in that abstract. And in this study, HLA-A*02:01 positive patients with advanced unresectable melanoma will be randomized one to one to the combination of IMC-F106C, which actually, I think after this meeting will be known as bre-ni in combination with nivolumab versus nivolumab regimens, which will either be nivo or nivo-rela, investigators choice and likely dependent on region. So what do you think of the challenge of this trial? We talked about some of the challenges of the TILVANCE trial earlier. But what is going to be the challenge of this trial and in this setting, particularly given the response rates that we've seen so far? Dr. Jason Luke: Yeah, so, similar to comments we had before, thinking about what the optimal control arm is for a study like this is difficult, and so that'll be important as we think about interpreting the results. One has to assume for the purpose of this conversation that it is a positive trial, and that adding the PRAME bispecific theory does lead to an improvement in progression free survival relative to those in checkpoint alone approaches. And I think the magnitude of that difference is going to be of some relevance. And then I think importantly, also figure out who needs this treatment and who's going to benefit long term are going to be really important considerations. We alluded to how this drug requires an intensive dosing period at the get go, and so telling patients that they need to come in weekly or bi-weekly initially for some number of weeks before they switch to a longer-term intermittent regimen, that comes with real world considerations for patients, their families, their finances, etc. So the benefit has to be clearly obvious that makes it worthwhile doing that, again, because a default could be giving drugs that we've had for 10 years with the nivolumab and ipilimumab. So there's going to be a lot of cross-trial comparison that is going to necessarily have to take place here to think about what these results really mean in the context of other available therapies. I think the study is reasonable to do. I think this is a very active agent. There's no doubt there's a subset of patients who seem to benefit a lot from it. And I would just emphasize the point that that's probably going to be the most important thing to really drill down on is under the assumption there's a positive trial, we need to know who those people are so we could optimize giving this kind of a treatment to them. Dr. Diwakar Davar: I guess one important point to underscore what Jason said about potential predictive biomarkers, I think as part of the presentation, Dr. Hamid and colleagues will be talking about a candidate predictive biomarker of this agent, which is potentially class specific and not necessarily agent specific of a T cell signature that potentially could define patients who are more likely to benefit from this agent. So, Jason, as always, thank you for sharing your expertise and insights with the team today. We certainly look forward to catching up again for our wrap up episode after the annual meeting where we'll talk about some of the data that we could not talk about, particularly the late breaking abstracts and other key advances that will shape the future of, certainly the field of immunotherapy and melanoma, potentially the field of cancer immunotherapy at large. Dr. Jason Luke: Oh, thanks very much for the opportunity. Dr. Diwakar Davar: And thank you to our listeners today. You'll find the links to the abstracts discussed today in the transcript of this episode. And finally, if you value the insights that you hear on this podcast, please take a moment to rate, review, and subscribe wherever you get your podcast. So thank you, and we'll see you soon. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:  Dr. Diwakar Davar  @diwakardavar  Dr. Jason Luke  @jasonlukemd    Follow ASCO on social media:   @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures:     Dr. Diwakar Davar:    Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences   Consulting or Advisory Role: Instil Bio, Vedanta Biosciences   Consulting or Advisory Role (Immediate family member): Shionogi   Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences   Research Funding (Inst.): Zucero Therapeutics   Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy     Dr. Jason Luke:   Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX   Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine   Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure   Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)   Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

united states university ai moving spring os pittsburgh phase fda pfizer keynote drs werewolf relation personalized pd immune bayer abstract ici merck cm endeavor janssen checkmate novartis melanoma relativity royalties lag 1a accommodations immunotherapy gsk ima hamid precision medicine asco genentech abbvie stipe bristol myers squibb takeda regeneron pfs chesney hla gilead sciences tcr adverse events nci nektar tfs onc prognostic cancer immunotherapy braf eisai cd3 tils asco annual meeting pyxis rubius servier steve rosenberg ctla ctdna emd serono incyte alnylam genmab moderna therapeutics tcrs tesaro jason luke m1a transcript dr recist array biopharma synlogic

A Revolution in Immunotherapy for Cervical and Endometrial Cancers

PeerView Heart, Lung & Blood CME/CNE/CPE Video Podcast

Play Episode Listen Later Apr 18, 2024 26:18

Doctors James Ferriss, Linda Duska, and Jayanthi Lea discuss the promise and the challenges of targeting the immune system with immune checkpoint inhibitors, or ICIs, in cervical and endometrial cancers. They also examine emerging data that support the use of ICIs in recurrent cervical cancer, the potential for curing some patients with advanced endometrial cancer, and molecular factors that make cervical cancer a good target for immunotherapy. TRANSCRIPT Dr. James Stuart Ferriss: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. James Stuart Ferriss, your guest host of the ASCO Daily News Podcast today. I'm an associate professor of gynecology and obstetrics and the Gynecologic Oncology Fellowship Program Director at Johns Hopkins Medicine. In today's episode, we'll be discussing the use of immunotherapy in cervical and endometrial cancers to advance the treatment of these malignancies. I'm delighted to be joined by two acclaimed experts in this space, Dr. Linda Duska and Dr. Jaya Lea. Dr. Duska is a professor of obstetrics and gynecology and serves as the associate dean for clinical research at the University of Virginia School of Medicine. Dr. Lea is a professor of obstetrics and gynecology and chief of gynecologic oncology at the University of Texas Southwestern Medical Center. Our full disclosures are available in the transcript of this episode, and disclosures related to all episodes of the podcast are available at asco.org/DNpod. Drs. Duska and Dr. Lea, it's great to have you on the podcast today. Dr. Linda Duska: Thanks, Dr. Ferriss. Dr. Jayanthi Lea: Thanks, Dr. Ferriss. Dr. James Stuart Ferriss: So, let's get started. In recent years, we've had a revolution in the treatment of advanced endometrial and cervical cancers with improved outcomes for patients treated with immunotherapy. And when we say immunotherapy, we're specifically talking about immune checkpoint inhibitors today. A few of these agents have actually been approved in the United States for the management of these diseases. In our discussion, I'd like to review the promise and challenges of targeting the immune system in patients with advanced endometrial and cervical cancers, as well as review the most recent evidence we have in these spaces. Let's start with cervix. We've had a lot of improvements in outcomes here, Dr. Lea, and with cervical cancer, we've seen improved overall survival with the incorporation of immunotherapy along with chemotherapy and anti-angiogenic therapy for advanced and recurrent disease. Can you remind us why cervical cancer is a good target for immunotherapy? Dr. Jayanthi Lea: Yes, Dr. Ferriss. Immunotherapy for cervical cancer is supported by several molecular factors. And I think first and foremost, it's so important to remember that the majority of cervical cancers are HPV-positive. And HPV-positive cancers can induce a high level of inflammation, but this high level of inflammation actually contributes to evasion of immune surveillance. What it also does is that it's responsible for the induction of PD-L1. And we've seen several studies that have shown that cervical cancers express PD-L1 anywhere from 50 to 90 percent of cases. Other pertinent factors to consider are that cervical cancer can be considered a tumor with a high tumor mutational burden. So, the number of somatic mutations that we see in the DNA can be considered as a proxy for neoantigens. And so the higher the level of neoantigens, the more immunogenic the tumor. And then lastly, about 1 in 10 cervical cancers present with microsatellite instability, which is an already established key biomarker for the response team in care. Dr. James Stuart Ferriss: So, thinking about targeting PD-L1, what clinical evidence do we have that supports the use of immune checkpoint inhibitors in recurrent cervical cancer? Dr. Jayanthi Lea: We now have several studies that have shown a benefit for immune checkpoint inhibitors. For example, KEYNOTE-158 was a phase 2 basket [trial] that investigated the antitumor activity of pembrolizumab, which is a PD-1 inhibitor, in multiple cancer types. And specifically for patients with previously treated advanced cervical cancer, we were able to see an overall response rate of about 15% in those patients who had PD-L1 positive. And similarly, the EMPOWER CERVICAL-1 study, which was a phase 3 randomized trial that investigated the efficacy of cemiplimab, which is another PD-1 inhibitor, versus investigator's choice of single agent chemotherapy, showed a significant difference in median overall survival and progression-free survival in the cemiplimab group. There are several other studies that have investigated the efficacy of PD-1 or PD-L1 inhibitors in cervical cancer. One specific PD-1 inhibitor is nivolumab. In CHECKMATE-358, nivolumab was associated with an overall response rate of 26% in women who had recurrent/metastatic cervical cancer. Dr. James Stuart Ferriss: Dr. Duska, do you have any thoughts? Dr. Linda Duska: I'm really interested in PD-L1 as a biomarker because in the KEYNOTE-A18 study, which we're going to get to, 95% of patients were PD-L1 positive by CPS, which is the scoring system that we use in cervix cancer. And some of the studies that you already mentioned, including BEATcc, which we're also going to talk about, reported results where PD-L1 wasn't even considered. And so it begs the question, since PD-L1 is actually – again, depending on when in the course of disease you look at it, but more recent studies suggest 95% of cervical cancers express PD-L1, and – agnostic is the word I was looking for – it seems at least in BEATcc and similar trials that PD-L1 is agnostic, but I wonder if PD-L1 is really a good biomarker for response to checkpoint inhibitor therapy and I wonder what your thoughts are. Dr. Jayanthi Lea: I think that's an excellent question. To your point, that's correct that we saw in KETYNOTE-A18 that more than 90% of the patients had PD-L1 positivity and the result is sort of generalizable to all comers. That's still a matter of debate as to how we see PD-L1 as a biomarker to incorporate checkpoint inhibitors in the treatment of patients. Dr. James Stuart Ferriss: So, let's talk about the use of immune checkpoint inhibitors in the frontline setting. Until recently, we haven't seen much improvement in overall survival since the introduction of anti-angiogenic therapy to the chemotherapy backbone, and that was in GOG 240. Let's talk about the changes that have recently occurred in this space. Dr. Jayanthi Lea: So, we've had some very exciting data specifically from initially KEYNOTE-826 and its primary metastatic or first line salvage settings. So, KEYNOTE-826, which was a phase 3 randomized, controlled trial was very practice-changing for us because it showed that incorporation of pembrolizumab to the first-line treatment of patients with metastatic or recurrent cervical cancer, really changed the landscape for treatment in this group of patients. So, keep in mind that prior to the study, the standard of care was carboplatin, or cisplatin with paclitaxel plus or minus bevacizumab, which yielded a median overall survival range in anywhere from 13 to 17 months depending on whether you use bevacizumab or not. And then adding pembrolizumab to that regimen, increase the median overall survival to 24 months, which is very promising. Dr. James Stuart Ferriss: If I remember correctly, KEYNOTE-826 allowed investigators choice, use of bevacizumab, and initially we were unsure about which regimen was best. Has there been additional data since? Dr. Jayanthi Lea: There has been additional data since. And another study that was done in the same vein was the BEATcc trial, which also looked at the different checkpoint inhibitors, atezolizumab in combination now with bevacizumab and platinum-based chemotherapy. And the control arm for this study was the GOG 240 regimen, which included bevacizumab. And this study showed both a progression-free and overall survival difference. The median overall survival in this study was 32 months with the incorporation of the checkpoint inhibitor to the bevacizumab and platinum-based chemotherapy. So, the way that I look at it is that the BEATcc trial basically confirmed the findings of KEYNOTE-826 and highlights that it is important for us to incorporate checkpoint inhibition with immunotherapy along with bevacizumab when we're treating patients with a recurrence. Dr. James Stuart Ferriss: Also, folks with primary advanced treatment for cervical cancer, this would be a great regimen, is that right? Dr. Jayanthi Lea: Absolutely. Primary advance, we would want to use the same regimen for that. Dr. James Stuart Ferriss: Okay. What about locally advanced in primary treatment? What advances have we seen? Dr. Jayanthi Lea: So we've had some major changes in that field as well, especially with the recent KEYNOTE-A18 data where pembrolizumab was administered in combination with external beam radiation and concurrent chemotherapy. And this study showed that there was significant and clinically meaningful improvement in progression-free survival compared to chemoradiation alone. Specifically, the progression-free survival at 24 months using pembrolizumab with chemoradiation was 68%, and 57% when in the placebo group. The hazard ratio for disease progression was 0.7 and no new safety signals were observed, which is fantastic, especially given the 0.7 hazard ratio that received PFS. Dr. James Stuart Ferriss: Yeah, absolutely. These patients with locally advanced cervical cancer often are quite symptomatic, and the prospect of adding chemo, radiation, and now immunotherapy on top of that is really encouraging to see that it was such a well-tolerated regimen. I believe that there were patient-reported outcomes recently reported at SGO. Dr. Jayanthi Lea: Absolutely. So, the safety profile of pembrolizumab and chemoradiation was consistent with the known profile of the individual treatment components. And no new safety signals emerged in the pembrolizumab chemoradiation arm. So, you're right. It was very well tolerated. Dr. James Stuart Ferriss: What would you say are the takeaways for folks who are seeing these patients in the community? These locally advanced cervical cancer patients that are now adding immunotherapy in a space that we have not used routinely in the past in terms of combining it with chemo radiation in gynecologic cancer. What are some things they should be looking out for? Dr. Jayanthi Lea: Well, I think that with the hazard ratio of 0.7 and the patient-reported outcomes showing no new signal, I think we can say that there is a positive benefit-to-risk profile of adding pembrolizumab in combination with chemoradiation, and that we should feel comfortable using this regimen. Now, of course, we have individualized patient care, and be able to know when to use bevacizumab, when to use immunotherapy. So, taking the whole patient into consideration becomes important. But for those individuals who are able to receive these drugs who don't have concrete issues to not receive these drugs [then I'd say we could] incorporate them since the safety profile is set. Dr. Linda Duska: I would add to that, Dr. Ferriss, that right now we only have FDA approval in the U.S. for stage 3-4A disease, and that's 2014 staging. Mind you, we are now in 2018, so we should be very careful in and follow the correct FIGO staging. But the FDA only gave approval for stage 3-4A disease, even though the study included patients with earlier stage disease and positive nodes. Dr. James Stuart Ferriss: That's a great point, thank you. So, Dr. Duska, thinking about endometrial cancer and advanced endometrial cancer, we have seen a similar revolution in the care of patients over the past few years, with major shifts in our approach. Can you remind us how we got here? Dr. Linda Duska: Yes, I would say in the ‘90s and before, and maybe even in the early 2000s, we used a lot of radiation for endometrial cancer as adjuvant therapy following surgery. The general consensus and what we were all taught was that this was a chemotherapy-resistant disease. And then we learned from a variety of GOG at the time, Gynecologic Oncology Group trials, that this disease is actually chemosensitive. And we went through a series of chemotherapy drugs, ranging from adriamycin cisplatin to taxel adriamycin cisplatin, and finally to taxel and carboplatin, demonstrating that this disease is actually quite chemosensitive. With this realization came the idea that maybe it would be important to combine chemotherapy and radiation particularly in high-risk endometrial cancer cases, so those with positive nodes or patients with high-risk histology such as clear cell or serous cancers. So two very important trials were done, one of them was PORTEC-3 and the other was GOG-258, which looked at combining chemo and radiation together to see if we could do better than one or the other alone. And they were very different trials, and they looked at different populations of patients and they looked at different things. For example, PORTEC-3 randomized patients to receive chemotherapy and radiation versus radiation alone, while 258 looked at chemotherapy and radiation versus chemotherapy alone. Without going into a great amount of detail, I think what we learned from both of those studies, and I think surprised many of us, that the arms that included chemotherapy, those patients did better. In fact, the results of GOG-258 can be interpreted – and this is somewhat controversial – but can be interpreted that many of these high-risk patients don't need radiation at all, or perhaps need tumor-directed radiation. For example, chemotherapy followed by tumor-directed radiation either to the vaginal cuff, because the vaginal cuff is at risk for recurrence, or perhaps to an area of concern, maybe the cervix if there were cervical involvement or if there is a particular concern for local recurrence in a particular patient. So, I think the pendulum has swung from almost always using radiation alone to, in more modern day, using chemotherapy and using radiation much more sparingly, and then comes immunotherapy. Dr. James Stuart Ferriss: So, update us on the results of NRG-GY018 and RUBY? Dr. Linda Duska: So, we've already talked about the KEYNOTE basket trials, which really contributed a lot to our understanding of the importance of MMR deficiency and microsatellite unstable disease. The KEYNOTE-158 study and the GARNET study showed us how important it was for women with MMRd and MSI endometrial cancer to receive checkpoint inhibition, and actually with remarkable response rates to women who had already been pretreated. But we also learned from the GARNET trial, which included MMRp patients, that the response rates in MMRp were not that great. And that led to KEYNOTE-775, which looked to combine pembrolizumab with a VEGF inhibitor, lenvantinib, to see if we could make the cold tumor hot. And indeed, we could. And not only could we improve the response rate in patients with MMRp tumors, but we could also improve the response rate in patients with MMRd tumors. They did better with the combination than they did with pembro alone. That led to the idea of combining checkpoint inhibitors with chemo upfront. The idea there was we were going to take paclitaxel and carboplatin, which were our backbone for advanced or recurrent endometrial cancer, and add immunotherapy to that. And to your point, GY018 and RUBY trials did just that. And they allowed MMRd and MMRp patients and combined paclitaxel and carboplatin, either with dostarlimab in the case of RUBY, or pembrolizumab in the case of GY018. These studies, both of which were reported and published in the New England Journal of Medicine last year, showed remarkable findings in the upfront setting and potentially in the curable setting. And the OS data for RUBY were presented at SGO this year and were remarkable for MMRd patients. In the whole population, in the whole group in RUBY, there was a 16.4-month improvement in overall survival with the addition of dostarlimab which is just huge. When you look at the MMRd group, I think Dr. Powell described the overall survival improvement as unprecedented. I believe that was the word that he used. Also, he called it very robust, with a hazard ratio of 0.32 for the group that got dostarlimab, and a median OS that was not reached. So really remarkable. In addition, in the MMRp group, there was a seven-month improvement in OS that was significant. So that's really amazing in the RUBY trial. It's also of note that the RUBY trial allowed carcinosarcomas, whereas the GY018 study did not. So, I think it's fair to say that these results apply to carcinosarcomas. It's also really important to note that many of the patients in the immunotherapy group who received placebo, 41% of them got IO in a later treatment line, and these OS data still stand. So that's really interesting and hypothesis-generating. For GY018, we don't have mature OS data yet, so we can't talk about OS. But we saw a similar improvement in PFS in both arms, in the d and the pMMR, with an OS trend in both arms that was also reported at SGO. GY018 was a little bit different though, because they unblinded at the time of the PFS reporting last year, and so those patients were unblinded a lot earlier than the RUBY patients were. So, to interpret the data in that vein, the OS data is not mature, but we anticipate looking at the PFS curves and the preliminary OS curves, that the OS data will also be statistically significantly improved in core pembrolizumab in GY018. What's also really interesting, and we haven't talked about molecular subtypes, is that when we look at the molecular subtypes in RUBY, and I'm sure we're going to see data on the molecular subtypes in GY018 coming up, different molecular subtypes of endometrial cancer respond differently to IO. And so, there's going to be lots of really interesting data coming our way soon that we're really excited to see, and that will help us triage patients appropriately into treatment regimens. Dr. James Stuart Ferriss: Dr. Lea, did you have a thought? Dr. Jayanthi Lea: Yeah, I just wanted to comment that looking at the dMMR survival curve in the file that was presented recently, one thing that really strikes me is the importance of adding the IO at the time of initial treatment. The separation of the curves persists. And, like you just mentioned, Dr. Duska, I mean, some of those patients who received placebo then later on went to get an IO treatment, but at the same time, we still see a vast separation of those curves. So, I think it's really important to note that immunotherapy should be used upfront, especially in dMMR. Dr. Linda Duska: Yeah, I completely agree with that. And I think that might be– I mean, this is just a hypothesis, but I think that that might be why we saw a difference with the addition of immunotherapy in the MMRp group, because it's possible that the chemotherapy created an immune environment that made the checkpoint inhibitor work more successfully than it would have otherwise. So, a really good point. You definitely need to include dostarlimab or pembrolizumab with the chemotherapy and then as maintenance therapy after. Dr. James Stuart Ferriss: So, you mentioned, we're increasingly thinking about endometrial cancer in smaller and smaller buckets of patients with very prescribed molecular profiles. We don't yet have enough information to specifically tailor treatment. How are you approaching that today in patients that you see in clinic? Dr. Linda Duska: Well, the MMR, and I'm interested in what you both are doing also, it's easy with the MMRd and MSI high patients. Those patients all should receive a checkpoint inhibitor, no question. The patients that are p53 mut, I test them for HER2, because we do have data to suggest that atezolizumab or TDX-d might be useful in those individuals, HER2 positive. And then the remaining patients, also called the NSMPs. That's a difficult group. I'm interested to know how you all manage them. I think that's the group where more clinical research is really needed to determine what the best treatment regimen for them is. But I'm interested in both of your thoughts on that. Dr. James Stuart Ferriss: Dr. Lea? Dr. Jayanthi Lea: I would have to say that I do exactly like you do, Dr. Duska. Dr. James Stuart Ferriss: And I would say our approach is very similar. And we have a robust discussion always about the use of immunotherapy with chemotherapy and in patients who are proficient MMR. But I think that most of us believe that the PFS data is certainly compelling. And now the OS data from RUBY, very compelling in both groups. And so, we are routinely recommending the use of immunotherapy along with chemotherapy in these advanced patients. Dr. Linda Duska: I've heard the argument made that GY018 required measurable disease, and so does not necessarily apply to patients without measurable disease. I'm not sure that I agree with that. I think there were clinical trial reasons why that was a requirement rather than biologic reasons. In addition, as we already discussed, RUBY included carcinosarcomas and GY018 did not. I don't think there's a reason to only use dostarlimab for carcinosarcomas, but that said, I don't know that pembrolizumab has an indication for carcinosarcomas. The devil's in the details, don't get too lost in the weeds. I think the take-home message here is that it's really important to use IO, particularly for the MMRd patients with endometrial cancer, upfront. And based on the OS that we saw in both RUBY and preliminarily in GY018, we may be curing some people with this regimen, and I think we should focus on that. The overall survival for advanced endometrial cancer is not great, and if we can improve that and potentially cure some people, that's a huge advance for our patients. Dr. James Stuart Ferriss: Do you envision a day that we might even ask the question, “Do we need to do surgery?” Dr. Linda Duska: So, the rectal data would support that assertion. I'm not sure that endometrial cancer and rectal cancer are the same thing. And I think that taking out a postmenopausal woman's uterus is a lot less morbid than potentially radiating or taking out somebody's rectum. I think a different question would be, is there a day when we would stop doing no dissection? We could definitely debate that, but I don't see that happening. Do you see that happening anytime soon? A stopping of hysterectomy for endometrial cancer? Dr. Jayanthi Lea: I don't see that happening anytime soon. And I think, as you said, taking out the uterus, tubes, and ovaries, it does provide us with some information about whether you're even dealing with a secondary primary. But also, it's from a quality-of-life standpoint. If a woman has a large uterus, that's uncomfortable. Postmenopausal bleeding, avoiding bleeding during the course of treatment, so many reasons why I wouldn't be in too much of a hurry to want to not do surgery for these patients. Dr. James Stuart Ferriss: So, we'll put a plug in for our fellow gynecologic oncologists that we still have a role to play in the incorporation of treatment regimens for patients with advanced uterine cancer. So it's not just medicine, there's still a role for surgery. Dr. Linda Duska: I think that's very fair, yeah. Dr. James Stuart Ferriss: Okay. I think that's all the time we have for today. I want to thank our listeners for their time, and you'll find the links to all the studies we've discussed today in the transcript of this episode. And finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you. Dr. Linda Duska: Thank you. Dr. Jayanthi Lea: Thank you. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers: Dr. James Stuart Ferriss Dr. Linda Duska @LDuska Dr. Jayanthi Lea Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. James Stuart Ferriss: Honoraria: National Board of Medical Examiners Dr. Linda Duska: Consulting or Advisory Role: Regeneron, Inovio Pharmaceuticals, Merck, Ellipses Pharma Researching Funding (Inst): GlaxoSmithKline, Millenium, Bristol-Myers Squibb, Aeterna Zentaris, Novartis, Abbvie, Tesaro, Cerulean Pharma, Aduro Biotech, Advaxis, Syndax, Pfizer, Merck, Genentech/Roche, Cerulean Pharma, Ludwig Institute for Cancer Research, Leap Therapeutics Patents, Royalties, Other Intellectual Property: UpToDate, Editor, British Journal of Ob/Gyn Dr. Jayanthi Lea: Consulting or Advisory Role: Roche

Benjamin Levy, MD - Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer

Play Episode Listen Later Mar 14, 2024 54:35

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UFJ865. CME/MOC/AAPA/IPCE credit will be available until March 23, 2025.Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerMarina Chiara Garassino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; OSE Immunotherapeutics; Pfizer; Regeneron Pharmaceuticals Inc.; Seattle Genetics, Inc.; and Takeda Pharmaceutical Company Ltd.Grant/Research Support from Research funding to institution for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; F. Hoffmann-La Roche Ltd.; Foundation Medicine, Inc.; GlaxoSmithKline; Lilly; Merck Sharp & Dohme Corp.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Spectrum Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Ltd.Speaker for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Takeda Pharmaceutical Company Ltd/Mirati Therapeutics, Inc.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; Puma Biotechnology, Inc.; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Faculty/PlannerZosia Piotrowska, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bayer Corporation; Blueprint Medicines Corporation; Boehringer Ingelheim International GmbH; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Sanofi; Taiho Oncology, Inc.; and Takeda Pharmaceutical Company Limited.Grant/Research Support from AbbVie Inc.; AstraZeneca; Blueprint Medicines Corporation; Cullinan Oncology, Inc; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Spectrum Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited; and Tesaro, Inc./GlaxoSmithKline.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

research speaker patients code md consultants delivery pfizer advisor cracking astrazeneca targeted peer pressure liu cracking the code medical education lung cancer sanofi genentech glaxosmithkline bristol myers squibb gilead sciences adcs planning committee ellipses accreditation council janssen pharmaceuticals regeneron pharmaceuticals daiichi sankyo jazz pharmaceuticals pvi foundation medicine benjamin levy continuing medical education accme abbvie inc seattle genetics bayer corporation pharmacy education acpe eisai inc celgene corporation cytotoxic mirati therapeutics practice aids tesaro hoffmann la roche ltd peerview institute reviewer disclosuresplanners grant research support disclosure policyall elevation oncology takeda pharmaceutical company limited cme moc aapa ipce boehringer ingelheim international gmbh blueprint medicines corporation turning point therapeutics hoffmann la roche ltd genentech

Benjamin Levy, MD - Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Mar 14, 2024 54:43

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UFJ865. CME/MOC/AAPA/IPCE credit will be available until March 23, 2025.Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerMarina Chiara Garassino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; OSE Immunotherapeutics; Pfizer; Regeneron Pharmaceuticals Inc.; Seattle Genetics, Inc.; and Takeda Pharmaceutical Company Ltd.Grant/Research Support from Research funding to institution for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; F. Hoffmann-La Roche Ltd.; Foundation Medicine, Inc.; GlaxoSmithKline; Lilly; Merck Sharp & Dohme Corp.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Spectrum Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Ltd.Speaker for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Takeda Pharmaceutical Company Ltd/Mirati Therapeutics, Inc.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; Puma Biotechnology, Inc.; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Faculty/PlannerZosia Piotrowska, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bayer Corporation; Blueprint Medicines Corporation; Boehringer Ingelheim International GmbH; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Sanofi; Taiho Oncology, Inc.; and Takeda Pharmaceutical Company Limited.Grant/Research Support from AbbVie Inc.; AstraZeneca; Blueprint Medicines Corporation; Cullinan Oncology, Inc; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Spectrum Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited; and Tesaro, Inc./GlaxoSmithKline.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

research speaker patients code md consultants delivery pfizer advisor cracking astrazeneca targeted peer pressure liu cracking the code medical education lung cancer sanofi genentech glaxosmithkline bristol myers squibb gilead sciences adcs planning committee ellipses accreditation council janssen pharmaceuticals regeneron pharmaceuticals daiichi sankyo jazz pharmaceuticals pvi foundation medicine benjamin levy continuing medical education accme abbvie inc seattle genetics bayer corporation pharmacy education acpe eisai inc celgene corporation cytotoxic mirati therapeutics practice aids tesaro hoffmann la roche ltd peerview institute reviewer disclosuresplanners grant research support disclosure policyall elevation oncology takeda pharmaceutical company limited cme moc aapa ipce boehringer ingelheim international gmbh blueprint medicines corporation turning point therapeutics hoffmann la roche ltd genentech

Benjamin Levy, MD - Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast

Play Episode Listen Later Mar 14, 2024 54:35

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UFJ865. CME/MOC/AAPA/IPCE credit will be available until March 23, 2025.Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerMarina Chiara Garassino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; OSE Immunotherapeutics; Pfizer; Regeneron Pharmaceuticals Inc.; Seattle Genetics, Inc.; and Takeda Pharmaceutical Company Ltd.Grant/Research Support from Research funding to institution for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; F. Hoffmann-La Roche Ltd.; Foundation Medicine, Inc.; GlaxoSmithKline; Lilly; Merck Sharp & Dohme Corp.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Spectrum Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Ltd.Speaker for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Takeda Pharmaceutical Company Ltd/Mirati Therapeutics, Inc.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; Puma Biotechnology, Inc.; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Faculty/PlannerZosia Piotrowska, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bayer Corporation; Blueprint Medicines Corporation; Boehringer Ingelheim International GmbH; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Sanofi; Taiho Oncology, Inc.; and Takeda Pharmaceutical Company Limited.Grant/Research Support from AbbVie Inc.; AstraZeneca; Blueprint Medicines Corporation; Cullinan Oncology, Inc; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Spectrum Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited; and Tesaro, Inc./GlaxoSmithKline.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

research speaker patients code md consultants delivery pfizer advisor cracking astrazeneca targeted peer pressure liu cracking the code medical education lung cancer sanofi genentech glaxosmithkline bristol myers squibb gilead sciences adcs planning committee ellipses accreditation council janssen pharmaceuticals regeneron pharmaceuticals daiichi sankyo jazz pharmaceuticals pvi foundation medicine benjamin levy continuing medical education accme abbvie inc seattle genetics bayer corporation pharmacy education acpe eisai inc celgene corporation cytotoxic mirati therapeutics practice aids tesaro hoffmann la roche ltd peerview institute reviewer disclosuresplanners grant research support disclosure policyall elevation oncology takeda pharmaceutical company limited cme moc aapa ipce boehringer ingelheim international gmbh blueprint medicines corporation turning point therapeutics hoffmann la roche ltd genentech

Benjamin Levy, MD - Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer

PeerView Internal Medicine CME/CNE/CPE Video Podcast

Play Episode Listen Later Mar 14, 2024 54:35

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UFJ865. CME/MOC/AAPA/IPCE credit will be available until March 23, 2025.Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerMarina Chiara Garassino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; OSE Immunotherapeutics; Pfizer; Regeneron Pharmaceuticals Inc.; Seattle Genetics, Inc.; and Takeda Pharmaceutical Company Ltd.Grant/Research Support from Research funding to institution for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; F. Hoffmann-La Roche Ltd.; Foundation Medicine, Inc.; GlaxoSmithKline; Lilly; Merck Sharp & Dohme Corp.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Spectrum Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Ltd.Speaker for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Takeda Pharmaceutical Company Ltd/Mirati Therapeutics, Inc.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; Puma Biotechnology, Inc.; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Faculty/PlannerZosia Piotrowska, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bayer Corporation; Blueprint Medicines Corporation; Boehringer Ingelheim International GmbH; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Sanofi; Taiho Oncology, Inc.; and Takeda Pharmaceutical Company Limited.Grant/Research Support from AbbVie Inc.; AstraZeneca; Blueprint Medicines Corporation; Cullinan Oncology, Inc; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Spectrum Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited; and Tesaro, Inc./GlaxoSmithKline.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

research speaker patients code md consultants delivery pfizer advisor cracking astrazeneca targeted peer pressure liu cracking the code medical education lung cancer sanofi genentech glaxosmithkline bristol myers squibb gilead sciences adcs planning committee ellipses accreditation council janssen pharmaceuticals regeneron pharmaceuticals daiichi sankyo jazz pharmaceuticals pvi foundation medicine benjamin levy continuing medical education accme abbvie inc seattle genetics bayer corporation pharmacy education acpe eisai inc celgene corporation cytotoxic mirati therapeutics practice aids tesaro hoffmann la roche ltd peerview institute reviewer disclosuresplanners grant research support disclosure policyall elevation oncology takeda pharmaceutical company limited cme moc aapa ipce boehringer ingelheim international gmbh blueprint medicines corporation turning point therapeutics hoffmann la roche ltd genentech

Benjamin Levy, MD - Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer

PeerView Internal Medicine CME/CNE/CPE Audio Podcast

Play Episode Listen Later Mar 14, 2024 54:43

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UFJ865. CME/MOC/AAPA/IPCE credit will be available until March 23, 2025.Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerMarina Chiara Garassino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; OSE Immunotherapeutics; Pfizer; Regeneron Pharmaceuticals Inc.; Seattle Genetics, Inc.; and Takeda Pharmaceutical Company Ltd.Grant/Research Support from Research funding to institution for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; F. Hoffmann-La Roche Ltd.; Foundation Medicine, Inc.; GlaxoSmithKline; Lilly; Merck Sharp & Dohme Corp.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Spectrum Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Ltd.Speaker for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Takeda Pharmaceutical Company Ltd/Mirati Therapeutics, Inc.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; Puma Biotechnology, Inc.; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Faculty/PlannerZosia Piotrowska, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bayer Corporation; Blueprint Medicines Corporation; Boehringer Ingelheim International GmbH; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Sanofi; Taiho Oncology, Inc.; and Takeda Pharmaceutical Company Limited.Grant/Research Support from AbbVie Inc.; AstraZeneca; Blueprint Medicines Corporation; Cullinan Oncology, Inc; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Spectrum Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited; and Tesaro, Inc./GlaxoSmithKline.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

research speaker patients code md consultants delivery pfizer advisor cracking astrazeneca targeted peer pressure liu cracking the code medical education lung cancer sanofi genentech glaxosmithkline bristol myers squibb gilead sciences adcs planning committee ellipses accreditation council janssen pharmaceuticals regeneron pharmaceuticals daiichi sankyo jazz pharmaceuticals pvi foundation medicine benjamin levy continuing medical education accme abbvie inc seattle genetics bayer corporation pharmacy education acpe eisai inc celgene corporation cytotoxic mirati therapeutics practice aids tesaro hoffmann la roche ltd peerview institute reviewer disclosuresplanners grant research support disclosure policyall elevation oncology takeda pharmaceutical company limited cme moc aapa ipce boehringer ingelheim international gmbh blueprint medicines corporation turning point therapeutics hoffmann la roche ltd genentech

Benjamin Levy, MD - Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer

PeerView Oncology & Hematology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Mar 14, 2024 54:43

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UFJ865. CME/MOC/AAPA/IPCE credit will be available until March 23, 2025.Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerMarina Chiara Garassino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; OSE Immunotherapeutics; Pfizer; Regeneron Pharmaceuticals Inc.; Seattle Genetics, Inc.; and Takeda Pharmaceutical Company Ltd.Grant/Research Support from Research funding to institution for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; F. Hoffmann-La Roche Ltd.; Foundation Medicine, Inc.; GlaxoSmithKline; Lilly; Merck Sharp & Dohme Corp.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Spectrum Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Ltd.Speaker for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Takeda Pharmaceutical Company Ltd/Mirati Therapeutics, Inc.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; Puma Biotechnology, Inc.; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Faculty/PlannerZosia Piotrowska, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bayer Corporation; Blueprint Medicines Corporation; Boehringer Ingelheim International GmbH; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Sanofi; Taiho Oncology, Inc.; and Takeda Pharmaceutical Company Limited.Grant/Research Support from AbbVie Inc.; AstraZeneca; Blueprint Medicines Corporation; Cullinan Oncology, Inc; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Spectrum Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited; and Tesaro, Inc./GlaxoSmithKline.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

research speaker patients code md consultants delivery pfizer advisor cracking astrazeneca targeted peer pressure liu cracking the code medical education lung cancer sanofi genentech glaxosmithkline bristol myers squibb gilead sciences adcs planning committee ellipses accreditation council janssen pharmaceuticals regeneron pharmaceuticals daiichi sankyo jazz pharmaceuticals pvi foundation medicine benjamin levy continuing medical education accme abbvie inc seattle genetics bayer corporation pharmacy education acpe eisai inc celgene corporation cytotoxic mirati therapeutics practice aids tesaro hoffmann la roche ltd peerview institute reviewer disclosuresplanners grant research support disclosure policyall elevation oncology takeda pharmaceutical company limited cme moc aapa ipce boehringer ingelheim international gmbh blueprint medicines corporation turning point therapeutics hoffmann la roche ltd genentech

Benjamin Levy, MD - Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer

PeerView Heart, Lung & Blood CME/CNE/CPE Audio Podcast

Play Episode Listen Later Mar 14, 2024 54:43

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UFJ865. CME/MOC/AAPA/IPCE credit will be available until March 23, 2025.Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerMarina Chiara Garassino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; OSE Immunotherapeutics; Pfizer; Regeneron Pharmaceuticals Inc.; Seattle Genetics, Inc.; and Takeda Pharmaceutical Company Ltd.Grant/Research Support from Research funding to institution for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; F. Hoffmann-La Roche Ltd.; Foundation Medicine, Inc.; GlaxoSmithKline; Lilly; Merck Sharp & Dohme Corp.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Spectrum Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Ltd.Speaker for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Takeda Pharmaceutical Company Ltd/Mirati Therapeutics, Inc.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; Puma Biotechnology, Inc.; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Faculty/PlannerZosia Piotrowska, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bayer Corporation; Blueprint Medicines Corporation; Boehringer Ingelheim International GmbH; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Sanofi; Taiho Oncology, Inc.; and Takeda Pharmaceutical Company Limited.Grant/Research Support from AbbVie Inc.; AstraZeneca; Blueprint Medicines Corporation; Cullinan Oncology, Inc; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Spectrum Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited; and Tesaro, Inc./GlaxoSmithKline.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

research speaker patients code md consultants delivery pfizer advisor cracking astrazeneca targeted peer pressure liu cracking the code medical education lung cancer sanofi genentech glaxosmithkline bristol myers squibb gilead sciences adcs planning committee ellipses accreditation council janssen pharmaceuticals regeneron pharmaceuticals daiichi sankyo jazz pharmaceuticals pvi foundation medicine benjamin levy continuing medical education accme abbvie inc seattle genetics bayer corporation pharmacy education acpe eisai inc celgene corporation cytotoxic mirati therapeutics practice aids tesaro hoffmann la roche ltd peerview institute reviewer disclosuresplanners grant research support disclosure policyall elevation oncology takeda pharmaceutical company limited cme moc aapa ipce boehringer ingelheim international gmbh blueprint medicines corporation turning point therapeutics hoffmann la roche ltd genentech

Benjamin Levy, MD - Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Mar 14, 2024 54:35

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/UFJ865. CME/MOC/AAPA/IPCE credit will be available until March 23, 2025.Peer Pressure: How Well Do You Know Your ADCs? Cracking the Code of Targeted Delivery of Cytotoxic Payloads in Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBenjamin Levy, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerMarina Chiara Garassino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; OSE Immunotherapeutics; Pfizer; Regeneron Pharmaceuticals Inc.; Seattle Genetics, Inc.; and Takeda Pharmaceutical Company Ltd.Grant/Research Support from Research funding to institution for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; F. Hoffmann-La Roche Ltd.; Foundation Medicine, Inc.; GlaxoSmithKline; Lilly; Merck Sharp & Dohme Corp.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Spectrum Pharmaceuticals, Inc.; and Takeda Pharmaceutical Company Ltd.Speaker for AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd.; Gilead Sciences, Inc.; Lilly; Mirati Therapeutics, Inc.; MSD International GmbH; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Takeda Pharmaceutical Company Ltd/Mirati Therapeutics, Inc.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; Puma Biotechnology, Inc.; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Faculty/PlannerZosia Piotrowska, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Bayer Corporation; Blueprint Medicines Corporation; Boehringer Ingelheim International GmbH; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Sanofi; Taiho Oncology, Inc.; and Takeda Pharmaceutical Company Limited.Grant/Research Support from AbbVie Inc.; AstraZeneca; Blueprint Medicines Corporation; Cullinan Oncology, Inc; Daiichi Sankyo, Inc.; Janssen Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Spectrum Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited; and Tesaro, Inc./GlaxoSmithKline.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

research speaker patients code md consultants delivery pfizer advisor cracking astrazeneca targeted peer pressure liu cracking the code medical education lung cancer sanofi genentech glaxosmithkline bristol myers squibb gilead sciences adcs planning committee ellipses accreditation council janssen pharmaceuticals regeneron pharmaceuticals daiichi sankyo jazz pharmaceuticals pvi foundation medicine benjamin levy continuing medical education accme abbvie inc seattle genetics bayer corporation pharmacy education acpe eisai inc celgene corporation cytotoxic mirati therapeutics practice aids tesaro hoffmann la roche ltd peerview institute reviewer disclosuresplanners grant research support disclosure policyall elevation oncology takeda pharmaceutical company limited cme moc aapa ipce boehringer ingelheim international gmbh blueprint medicines corporation turning point therapeutics hoffmann la roche ltd genentech

Erika Hamilton, MD - Simplifying the Complicated: An Algorithmic Guide for Clinical Decision-Making in HR+, HER2- EBC and MBC

Play Episode Listen Later Feb 20, 2024 59:56

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/KBV865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 17, 2025.Simplifying the Complicated: An Algorithmic Guide for Clinical Decision-Making in HR+, HER2- EBC and MBC In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerProfessor Stephen Johnston, MA, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Lilly; Novartis Pharmaceuticals Corporation; Pfizer; Puma Biotechnology, Inc.; and Sanofi.Grant/Research Support from AstraZeneca; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Lilly; Novartis Pharmaceuticals Corporation; Pfizer; and Puma Biotechnology, Inc.Speakers Bureau participant with AstraZeneca; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; and Pfizer.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

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Erika Hamilton, MD - Simplifying the Complicated: An Algorithmic Guide for Clinical Decision-Making in HR+, HER2- EBC and MBC

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast

Play Episode Listen Later Feb 20, 2024 59:56

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/KBV865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 17, 2025.Simplifying the Complicated: An Algorithmic Guide for Clinical Decision-Making in HR+, HER2- EBC and MBC In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerProfessor Stephen Johnston, MA, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Lilly; Novartis Pharmaceuticals Corporation; Pfizer; Puma Biotechnology, Inc.; and Sanofi.Grant/Research Support from AstraZeneca; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Lilly; Novartis Pharmaceuticals Corporation; Pfizer; and Puma Biotechnology, Inc.Speakers Bureau participant with AstraZeneca; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; and Pfizer.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

guide phd patients md llc consultants pfizer advisor complicated simplifying astrazeneca medical education sanofi algorithmic genentech bristol myers squibb dana farber cancer institute her2 gilead sciences planning committee speakers bureau accreditation council curis janssen pharmaceuticals clinical decision making daiichi sankyo emd serono incyte pvi medimmune continuing medical education accme abbvie inc seattle genetics pharmamar pharmacy education acpe blueprint medicines eisai inc practice aids erika hamilton compugen peerview institute tesaro reviewer disclosuresplanners grant research support disclosure policyall seagen inc arvinas iteos therapeutics sutro biopharma karyopharm g1 therapeutics millennium pharmaceuticals arcus biosciences cme moc ncpd cpe aapa ipce scorpion therapeutics sermonix pharmaceuticals syros pharmaceuticals effector therapeutics acerta pharma rgenix inc zymeworks inc hoffmann la roche ltd genentech

Erika Hamilton, MD - Simplifying the Complicated: An Algorithmic Guide for Clinical Decision-Making in HR+, HER2- EBC and MBC

PeerView Oncology & Hematology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Feb 20, 2024 59:56

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/KBV865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 17, 2025.Simplifying the Complicated: An Algorithmic Guide for Clinical Decision-Making in HR+, HER2- EBC and MBC In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerProfessor Stephen Johnston, MA, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Lilly; Novartis Pharmaceuticals Corporation; Pfizer; Puma Biotechnology, Inc.; and Sanofi.Grant/Research Support from AstraZeneca; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Lilly; Novartis Pharmaceuticals Corporation; Pfizer; and Puma Biotechnology, Inc.Speakers Bureau participant with AstraZeneca; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; and Pfizer.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

guide phd patients md llc consultants pfizer advisor complicated simplifying astrazeneca medical education sanofi algorithmic genentech bristol myers squibb dana farber cancer institute her2 gilead sciences planning committee speakers bureau accreditation council curis janssen pharmaceuticals clinical decision making daiichi sankyo emd serono incyte pvi medimmune continuing medical education accme abbvie inc seattle genetics pharmamar pharmacy education acpe blueprint medicines eisai inc practice aids erika hamilton compugen peerview institute tesaro reviewer disclosuresplanners grant research support disclosure policyall seagen inc arvinas iteos therapeutics sutro biopharma karyopharm g1 therapeutics millennium pharmaceuticals arcus biosciences cme moc ncpd cpe aapa ipce scorpion therapeutics sermonix pharmaceuticals syros pharmaceuticals effector therapeutics acerta pharma rgenix inc zymeworks inc hoffmann la roche ltd genentech

Erika Hamilton, MD - Simplifying the Complicated: An Algorithmic Guide for Clinical Decision-Making in HR+, HER2- EBC and MBC

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Feb 20, 2024 59:56

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/KBV865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 17, 2025.Simplifying the Complicated: An Algorithmic Guide for Clinical Decision-Making in HR+, HER2- EBC and MBC In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Lilly.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerProfessor Stephen Johnston, MA, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Lilly; Novartis Pharmaceuticals Corporation; Pfizer; Puma Biotechnology, Inc.; and Sanofi.Grant/Research Support from AstraZeneca; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Lilly; Novartis Pharmaceuticals Corporation; Pfizer; and Puma Biotechnology, Inc.Speakers Bureau participant with AstraZeneca; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; and Pfizer.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

guide phd patients md llc consultants pfizer advisor complicated simplifying astrazeneca medical education sanofi algorithmic genentech bristol myers squibb dana farber cancer institute her2 gilead sciences planning committee speakers bureau accreditation council curis janssen pharmaceuticals clinical decision making daiichi sankyo emd serono incyte pvi medimmune continuing medical education accme abbvie inc seattle genetics pharmamar pharmacy education acpe blueprint medicines eisai inc practice aids erika hamilton compugen peerview institute tesaro reviewer disclosuresplanners grant research support disclosure policyall seagen inc arvinas iteos therapeutics sutro biopharma karyopharm g1 therapeutics millennium pharmaceuticals arcus biosciences cme moc ncpd cpe aapa ipce scorpion therapeutics sermonix pharmaceuticals syros pharmaceuticals effector therapeutics acerta pharma rgenix inc zymeworks inc hoffmann la roche ltd genentech

Erika Hamilton, MD - Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies

Play Episode Listen Later Jan 31, 2024 83:16

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/GHA865. CME/MOC/AAPA credit will be available until January 6, 2025.Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, GRASP, and Living Beyond Breast Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Lilly, and Olema Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerHope S. Rugo, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Daiichi Sankyo, Inc.; Mylan/Viatris Inc.; Napo Pharmaceuticals, Inc.; and Puma Biotechnology, Inc.Grant/Research Support from AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer; Pionyr Immunotherapeutics; Sermonix Pharmaceuticals; and Stemline Therapeutics.Faculty/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

art patients testing md llc hamilton treatments mastering consultants pfizer advisor selection astrazeneca precision mastering the art therapies grasp medical education risk assessment sequencing genentech cancer risk bristol myers squibb dana farber cancer institute gilead sciences metastatic breast cancer planning committee prognostic accreditation council curis janssen pharmaceuticals daiichi sankyo emd serono incyte pvi fasco living beyond breast cancer medimmune continuing medical education accme abbvie inc seattle genetics pharmamar pharmacy education acpe rugo blueprint medicines eisai inc practice aids compugen tesaro peerview institute erika hamilton reviewer disclosuresplanners grant research support disclosure policyall seagen inc arvinas iteos therapeutics sutro biopharma karyopharm arcus biosciences cme moc aapa g1 therapeutics millennium pharmaceuticals scorpion therapeutics effector therapeutics sermonix pharmaceuticals syros pharmaceuticals acerta pharma rgenix inc zymeworks inc hoffmann la roche ltd genentech

Erika Hamilton, MD - Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast

Play Episode Listen Later Jan 31, 2024 85:24

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/GHA865. CME/MOC/AAPA credit will be available until January 6, 2025.Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, GRASP, and Living Beyond Breast Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Lilly, and Olema Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerHope S. Rugo, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Daiichi Sankyo, Inc.; Mylan/Viatris Inc.; Napo Pharmaceuticals, Inc.; and Puma Biotechnology, Inc.Grant/Research Support from AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer; Pionyr Immunotherapeutics; Sermonix Pharmaceuticals; and Stemline Therapeutics.Faculty/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

art patients testing md llc hamilton treatments mastering consultants pfizer advisor selection astrazeneca precision mastering the art therapies grasp medical education risk assessment sequencing genentech cancer risk bristol myers squibb dana farber cancer institute gilead sciences metastatic breast cancer planning committee prognostic accreditation council curis janssen pharmaceuticals daiichi sankyo emd serono incyte pvi fasco living beyond breast cancer medimmune continuing medical education accme abbvie inc seattle genetics pharmamar pharmacy education acpe rugo blueprint medicines eisai inc practice aids compugen tesaro peerview institute erika hamilton reviewer disclosuresplanners grant research support disclosure policyall seagen inc arvinas iteos therapeutics sutro biopharma karyopharm arcus biosciences cme moc aapa g1 therapeutics millennium pharmaceuticals scorpion therapeutics effector therapeutics sermonix pharmaceuticals syros pharmaceuticals acerta pharma rgenix inc zymeworks inc hoffmann la roche ltd genentech

Erika Hamilton, MD - Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies

PeerView Internal Medicine CME/CNE/CPE Video Podcast

Play Episode Listen Later Jan 31, 2024 85:24

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/GHA865. CME/MOC/AAPA credit will be available until January 6, 2025.Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, GRASP, and Living Beyond Breast Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Lilly, and Olema Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerHope S. Rugo, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Daiichi Sankyo, Inc.; Mylan/Viatris Inc.; Napo Pharmaceuticals, Inc.; and Puma Biotechnology, Inc.Grant/Research Support from AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer; Pionyr Immunotherapeutics; Sermonix Pharmaceuticals; and Stemline Therapeutics.Faculty/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

art patients testing md llc hamilton treatments mastering consultants pfizer advisor selection astrazeneca precision mastering the art therapies grasp medical education risk assessment sequencing genentech cancer risk bristol myers squibb dana farber cancer institute gilead sciences metastatic breast cancer planning committee prognostic accreditation council curis janssen pharmaceuticals daiichi sankyo emd serono incyte pvi fasco living beyond breast cancer medimmune continuing medical education accme abbvie inc seattle genetics pharmamar pharmacy education acpe rugo blueprint medicines eisai inc practice aids compugen tesaro peerview institute erika hamilton reviewer disclosuresplanners grant research support disclosure policyall seagen inc arvinas iteos therapeutics sutro biopharma karyopharm arcus biosciences cme moc aapa g1 therapeutics millennium pharmaceuticals scorpion therapeutics effector therapeutics sermonix pharmaceuticals syros pharmaceuticals acerta pharma rgenix inc zymeworks inc hoffmann la roche ltd genentech

Erika Hamilton, MD - Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies

PeerView Internal Medicine CME/CNE/CPE Audio Podcast

Play Episode Listen Later Jan 31, 2024 83:16

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/GHA865. CME/MOC/AAPA credit will be available until January 6, 2025.Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, GRASP, and Living Beyond Breast Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Lilly, and Olema Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerHope S. Rugo, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Daiichi Sankyo, Inc.; Mylan/Viatris Inc.; Napo Pharmaceuticals, Inc.; and Puma Biotechnology, Inc.Grant/Research Support from AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer; Pionyr Immunotherapeutics; Sermonix Pharmaceuticals; and Stemline Therapeutics.Faculty/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

art patients testing md llc hamilton treatments mastering consultants pfizer advisor selection astrazeneca precision mastering the art therapies grasp medical education risk assessment sequencing genentech cancer risk bristol myers squibb dana farber cancer institute gilead sciences metastatic breast cancer planning committee prognostic accreditation council curis janssen pharmaceuticals daiichi sankyo emd serono incyte pvi fasco living beyond breast cancer medimmune continuing medical education accme abbvie inc seattle genetics pharmamar pharmacy education acpe rugo blueprint medicines eisai inc practice aids compugen tesaro peerview institute erika hamilton reviewer disclosuresplanners grant research support disclosure policyall seagen inc arvinas iteos therapeutics sutro biopharma karyopharm arcus biosciences cme moc aapa g1 therapeutics millennium pharmaceuticals scorpion therapeutics effector therapeutics sermonix pharmaceuticals syros pharmaceuticals acerta pharma rgenix inc zymeworks inc hoffmann la roche ltd genentech

Erika Hamilton, MD - Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies

PeerView Oncology & Hematology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Jan 31, 2024 83:16

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/GHA865. CME/MOC/AAPA credit will be available until January 6, 2025.Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, GRASP, and Living Beyond Breast Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Lilly, and Olema Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerHope S. Rugo, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Daiichi Sankyo, Inc.; Mylan/Viatris Inc.; Napo Pharmaceuticals, Inc.; and Puma Biotechnology, Inc.Grant/Research Support from AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer; Pionyr Immunotherapeutics; Sermonix Pharmaceuticals; and Stemline Therapeutics.Faculty/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

art patients testing md llc hamilton treatments mastering consultants pfizer advisor selection astrazeneca precision mastering the art therapies grasp medical education risk assessment sequencing genentech cancer risk bristol myers squibb dana farber cancer institute gilead sciences metastatic breast cancer planning committee prognostic accreditation council curis janssen pharmaceuticals daiichi sankyo emd serono incyte pvi fasco living beyond breast cancer medimmune continuing medical education accme abbvie inc seattle genetics pharmamar pharmacy education acpe rugo blueprint medicines eisai inc practice aids compugen tesaro peerview institute erika hamilton reviewer disclosuresplanners grant research support disclosure policyall seagen inc arvinas iteos therapeutics sutro biopharma karyopharm arcus biosciences cme moc aapa g1 therapeutics millennium pharmaceuticals scorpion therapeutics effector therapeutics sermonix pharmaceuticals syros pharmaceuticals acerta pharma rgenix inc zymeworks inc hoffmann la roche ltd genentech

Erika Hamilton, MD - Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Jan 31, 2024 85:24

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/GHA865. CME/MOC/AAPA credit will be available until January 6, 2025.Mastering the Art of Precision in the Treatment of HR+ Early and Metastatic Breast Cancer: Risk Assessment, Prognostic Testing, and Selection and Sequencing of Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, GRASP, and Living Beyond Breast Cancer. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Lilly, and Olema Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, Inc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, Inc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer Ingelheim Pharmaceuticals, Inc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; ImmunoGen, Inc.; Immunomedics, Inc.; Incyte; Infinity Pharmaceuticals, Inc.; InvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, Inc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; MedImmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove Inc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr Immunotherapeutics; Plexxikon; Radius Health, Inc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen Inc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, Inc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; TapImmune Inc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks Inc. (all paid to institution).Faculty/PlannerKomal Jhaveri, MD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Blueprint Medicines; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Eisai Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Jounce Therapeutics, Inc.; Lilly/Loxo Oncology; Menarini Group/Stemline Therapeutics; Novartis Pharmaceuticals Corporation; Pfizer; Scorpion Therapeutics; Seattle Genetics, Inc. (Seagen Inc.); Sun Pharma Advanced Research Company; and Taiho Oncology, Inc.Grant/Research Support from ADC Therapeutics SA; AstraZeneca; Blueprint Medicines; Debiopharm; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Novita Pharmaceuticals, Inc.; Pfizer; Puma Biotechnology, Inc.; Scorpion Therapeutics; and Zymeworks Inc.Faculty/PlannerHope S. Rugo, MD, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Daiichi Sankyo, Inc.; Mylan/Viatris Inc.; Napo Pharmaceuticals, Inc.; and Puma Biotechnology, Inc.Grant/Research Support from AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; OBI Pharma, Inc.; Pfizer; Pionyr Immunotherapeutics; Sermonix Pharmaceuticals; and Stemline Therapeutics.Faculty/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

art patients testing md llc hamilton treatments mastering consultants pfizer advisor selection astrazeneca precision mastering the art therapies grasp medical education risk assessment sequencing genentech cancer risk bristol myers squibb dana farber cancer institute gilead sciences metastatic breast cancer planning committee prognostic accreditation council curis janssen pharmaceuticals daiichi sankyo emd serono incyte pvi fasco living beyond breast cancer medimmune continuing medical education accme abbvie inc seattle genetics pharmamar pharmacy education acpe rugo blueprint medicines eisai inc practice aids compugen tesaro peerview institute erika hamilton reviewer disclosuresplanners grant research support disclosure policyall seagen inc arvinas iteos therapeutics sutro biopharma karyopharm arcus biosciences cme moc aapa g1 therapeutics millennium pharmaceuticals scorpion therapeutics effector therapeutics sermonix pharmaceuticals syros pharmaceuticals acerta pharma rgenix inc zymeworks inc hoffmann la roche ltd genentech

Bradley J. Monk, MD, FACS, FACOG - The ABCs of ADCs for Gynecologic Cancer: Expert Insights on Effective Implementation and Practical Tips for Use in Patients With Cervical, Ovarian, or Endometrial Cancer

Play Episode Listen Later Dec 13, 2023 40:44

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/BVX865. CME/MOC/AAPA/IPCE credit will be available until December 10, 2024.The ABCs of ADCs for Gynecologic Cancer: Expert Insights on Effective Implementation and Practical Tips for Use in Patients With Cervical, Ovarian, or Endometrial Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., Eisai Inc., and Seagen and Genmab.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBradley J. Monk, MD, FACS, FACOG, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Acrivon Therapeutics; Adaptimmune Therapeutics plc.; Agenus Inc.; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; AstraZeneca; Bayer Corporation; Clovis Oncology; Eisai Inc.; Elevar, LLC; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd./Genentech, Inc.; Genmab A/S/Seagen Inc.; The GOG Foundation Inc; Gradalis, Inc.; ImmunoGen, Inc.; Iovance Biotherapeutics, Inc.; Jiangsu Hengrui Pharmaceuticals Co., Ltd.; Karyopharm; Laekna Therapeutics; Merck & Co., Inc.; Mersana Therapeutics; Myriad Genetics, Inc.; Novartis Pharmaceuticals Corporation; Novocure GmbH; OncoC4, Inc.; Panavance Therapeutics Inc.; Pfizer; Pieris Pharmaceuticals, Inc.; Puma Biotechnology, Inc.; Regeneron Pharmaceuticals Inc.; Sorrento Therapeutics, Inc.; TESARO, Inc./GlaxoSmithKline; US Oncology Research, LLC; VBL Therapeutics; Verastem, Inc.; and Zentalis Pharmaceuticals.Grant/Research Support from US Oncology Research, LLC.Speaker for AstraZeneca; Clovis Oncology; Eisai Inc.; F. Hoffmann-La Roche Ltd./Genentech, Inc.; Merck & Co., Inc.; and TESARO, Inc./GlaxoSmithKline.Faculty/PlannerAna Oaknin, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Agenus Inc.; AstraZeneca; Clovis Oncology; Corcept Therapeutics; Deciphera Pharmaceuticals; Eisai Co., Ltd.; EMD Serono; Exelisis, Inc.; F. Hoffmann-La Roche; Genmab A/S; GlaxoSmithKline; ImmunoGen, Inc.; iTeos Therapeutics; Merck Sharp & Dohme de Espana SA; Mersana Therapeutics; Novocure GmbH; OncXerna Therapeutics, Inc.; Pharma Mar SA; Regeneron Pharmaceuticals Inc.; Seagen, Inc.; Shattuck Labs, Inc.; and Sutro Biopharma, Inc.Grant/Research Support from AbbVie Deutschland; Advaxis Inc.; Aeterna Zentaris; Amgen Inc.; Aprea Therapeutics AB; Bristol Myers Squibb; Clovis Oncology; Eisai Co., Ltd.; F. Hoffmann-La Roche; ImmunoGen, Inc.; Merck Sharp & Dohme de Espana SA; Millennium Pharmaceuticals Inc.; Pharma Mar SA; Regeneron Pharmaceuticals Inc; and Tesaro.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

phd speaker patients md llc consultants pfizer advisor monk implementation astrazeneca abcs practical tips medical education cervical expert insights facs genentech elevar ovarian glaxosmithkline bristol myers squibb adcs planning committee endometrial cancer accreditation council daiichi sankyo seagen gynecologic cancers myriad genetics emd serono pvi genmab continuing medical education accme bayer corporation pharmacy education acpe eisai inc merck sharp dohme practice aids eisai co hoffmann la roche ltd peerview institute tesaro reviewer disclosuresplanners grant research support disclosure policyall karyopharm sutro biopharma iteos therapeutics cme moc aapa ipce bradley j monk

Bradley J. Monk, MD, FACS, FACOG - The ABCs of ADCs for Gynecologic Cancer: Expert Insights on Effective Implementation and Practical Tips for Use in Patients With Cervical, Ovarian, or Endometrial Cancer

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast

Play Episode Listen Later Dec 13, 2023 40:36

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/BVX865. CME/MOC/AAPA/IPCE credit will be available until December 10, 2024.The ABCs of ADCs for Gynecologic Cancer: Expert Insights on Effective Implementation and Practical Tips for Use in Patients With Cervical, Ovarian, or Endometrial Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., Eisai Inc., and Seagen and Genmab.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBradley J. Monk, MD, FACS, FACOG, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Acrivon Therapeutics; Adaptimmune Therapeutics plc.; Agenus Inc.; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; AstraZeneca; Bayer Corporation; Clovis Oncology; Eisai Inc.; Elevar, LLC; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd./Genentech, Inc.; Genmab A/S/Seagen Inc.; The GOG Foundation Inc; Gradalis, Inc.; ImmunoGen, Inc.; Iovance Biotherapeutics, Inc.; Jiangsu Hengrui Pharmaceuticals Co., Ltd.; Karyopharm; Laekna Therapeutics; Merck & Co., Inc.; Mersana Therapeutics; Myriad Genetics, Inc.; Novartis Pharmaceuticals Corporation; Novocure GmbH; OncoC4, Inc.; Panavance Therapeutics Inc.; Pfizer; Pieris Pharmaceuticals, Inc.; Puma Biotechnology, Inc.; Regeneron Pharmaceuticals Inc.; Sorrento Therapeutics, Inc.; TESARO, Inc./GlaxoSmithKline; US Oncology Research, LLC; VBL Therapeutics; Verastem, Inc.; and Zentalis Pharmaceuticals.Grant/Research Support from US Oncology Research, LLC.Speaker for AstraZeneca; Clovis Oncology; Eisai Inc.; F. Hoffmann-La Roche Ltd./Genentech, Inc.; Merck & Co., Inc.; and TESARO, Inc./GlaxoSmithKline.Faculty/PlannerAna Oaknin, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Agenus Inc.; AstraZeneca; Clovis Oncology; Corcept Therapeutics; Deciphera Pharmaceuticals; Eisai Co., Ltd.; EMD Serono; Exelisis, Inc.; F. Hoffmann-La Roche; Genmab A/S; GlaxoSmithKline; ImmunoGen, Inc.; iTeos Therapeutics; Merck Sharp & Dohme de Espana SA; Mersana Therapeutics; Novocure GmbH; OncXerna Therapeutics, Inc.; Pharma Mar SA; Regeneron Pharmaceuticals Inc.; Seagen, Inc.; Shattuck Labs, Inc.; and Sutro Biopharma, Inc.Grant/Research Support from AbbVie Deutschland; Advaxis Inc.; Aeterna Zentaris; Amgen Inc.; Aprea Therapeutics AB; Bristol Myers Squibb; Clovis Oncology; Eisai Co., Ltd.; F. Hoffmann-La Roche; ImmunoGen, Inc.; Merck Sharp & Dohme de Espana SA; Millennium Pharmaceuticals Inc.; Pharma Mar SA; Regeneron Pharmaceuticals Inc; and Tesaro.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

phd speaker patients md llc consultants pfizer advisor monk implementation astrazeneca abcs practical tips medical education cervical expert insights facs genentech elevar ovarian glaxosmithkline bristol myers squibb adcs planning committee endometrial cancer accreditation council daiichi sankyo seagen gynecologic cancers myriad genetics emd serono pvi genmab continuing medical education accme bayer corporation pharmacy education acpe eisai inc merck sharp dohme practice aids eisai co hoffmann la roche ltd peerview institute tesaro reviewer disclosuresplanners grant research support disclosure policyall karyopharm sutro biopharma iteos therapeutics cme moc aapa ipce bradley j monk

Bradley J. Monk, MD, FACS, FACOG - The ABCs of ADCs for Gynecologic Cancer: Expert Insights on Effective Implementation and Practical Tips for Use in Patients With Cervical, Ovarian, or Endometrial Cancer

PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Video Podcast

Play Episode Listen Later Dec 13, 2023 40:36

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/BVX865. CME/MOC/AAPA/IPCE credit will be available until December 10, 2024.The ABCs of ADCs for Gynecologic Cancer: Expert Insights on Effective Implementation and Practical Tips for Use in Patients With Cervical, Ovarian, or Endometrial Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., Eisai Inc., and Seagen and Genmab.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBradley J. Monk, MD, FACS, FACOG, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Acrivon Therapeutics; Adaptimmune Therapeutics plc.; Agenus Inc.; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; AstraZeneca; Bayer Corporation; Clovis Oncology; Eisai Inc.; Elevar, LLC; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd./Genentech, Inc.; Genmab A/S/Seagen Inc.; The GOG Foundation Inc; Gradalis, Inc.; ImmunoGen, Inc.; Iovance Biotherapeutics, Inc.; Jiangsu Hengrui Pharmaceuticals Co., Ltd.; Karyopharm; Laekna Therapeutics; Merck & Co., Inc.; Mersana Therapeutics; Myriad Genetics, Inc.; Novartis Pharmaceuticals Corporation; Novocure GmbH; OncoC4, Inc.; Panavance Therapeutics Inc.; Pfizer; Pieris Pharmaceuticals, Inc.; Puma Biotechnology, Inc.; Regeneron Pharmaceuticals Inc.; Sorrento Therapeutics, Inc.; TESARO, Inc./GlaxoSmithKline; US Oncology Research, LLC; VBL Therapeutics; Verastem, Inc.; and Zentalis Pharmaceuticals.Grant/Research Support from US Oncology Research, LLC.Speaker for AstraZeneca; Clovis Oncology; Eisai Inc.; F. Hoffmann-La Roche Ltd./Genentech, Inc.; Merck & Co., Inc.; and TESARO, Inc./GlaxoSmithKline.Faculty/PlannerAna Oaknin, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Agenus Inc.; AstraZeneca; Clovis Oncology; Corcept Therapeutics; Deciphera Pharmaceuticals; Eisai Co., Ltd.; EMD Serono; Exelisis, Inc.; F. Hoffmann-La Roche; Genmab A/S; GlaxoSmithKline; ImmunoGen, Inc.; iTeos Therapeutics; Merck Sharp & Dohme de Espana SA; Mersana Therapeutics; Novocure GmbH; OncXerna Therapeutics, Inc.; Pharma Mar SA; Regeneron Pharmaceuticals Inc.; Seagen, Inc.; Shattuck Labs, Inc.; and Sutro Biopharma, Inc.Grant/Research Support from AbbVie Deutschland; Advaxis Inc.; Aeterna Zentaris; Amgen Inc.; Aprea Therapeutics AB; Bristol Myers Squibb; Clovis Oncology; Eisai Co., Ltd.; F. Hoffmann-La Roche; ImmunoGen, Inc.; Merck Sharp & Dohme de Espana SA; Millennium Pharmaceuticals Inc.; Pharma Mar SA; Regeneron Pharmaceuticals Inc; and Tesaro.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

phd speaker patients md llc consultants pfizer advisor monk implementation astrazeneca abcs practical tips medical education cervical expert insights facs genentech elevar ovarian glaxosmithkline bristol myers squibb adcs planning committee endometrial cancer accreditation council daiichi sankyo seagen gynecologic cancers myriad genetics emd serono pvi genmab continuing medical education accme bayer corporation pharmacy education acpe eisai inc merck sharp dohme practice aids eisai co hoffmann la roche ltd peerview institute tesaro reviewer disclosuresplanners grant research support disclosure policyall karyopharm sutro biopharma iteos therapeutics cme moc aapa ipce bradley j monk

Bradley J. Monk, MD, FACS, FACOG - The ABCs of ADCs for Gynecologic Cancer: Expert Insights on Effective Implementation and Practical Tips for Use in Patients With Cervical, Ovarian, or Endometrial Cancer

PeerView Oncology & Hematology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Dec 13, 2023 40:44

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/BVX865. CME/MOC/AAPA/IPCE credit will be available until December 10, 2024.The ABCs of ADCs for Gynecologic Cancer: Expert Insights on Effective Implementation and Practical Tips for Use in Patients With Cervical, Ovarian, or Endometrial Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., Eisai Inc., and Seagen and Genmab.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBradley J. Monk, MD, FACS, FACOG, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Acrivon Therapeutics; Adaptimmune Therapeutics plc.; Agenus Inc.; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; AstraZeneca; Bayer Corporation; Clovis Oncology; Eisai Inc.; Elevar, LLC; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd./Genentech, Inc.; Genmab A/S/Seagen Inc.; The GOG Foundation Inc; Gradalis, Inc.; ImmunoGen, Inc.; Iovance Biotherapeutics, Inc.; Jiangsu Hengrui Pharmaceuticals Co., Ltd.; Karyopharm; Laekna Therapeutics; Merck & Co., Inc.; Mersana Therapeutics; Myriad Genetics, Inc.; Novartis Pharmaceuticals Corporation; Novocure GmbH; OncoC4, Inc.; Panavance Therapeutics Inc.; Pfizer; Pieris Pharmaceuticals, Inc.; Puma Biotechnology, Inc.; Regeneron Pharmaceuticals Inc.; Sorrento Therapeutics, Inc.; TESARO, Inc./GlaxoSmithKline; US Oncology Research, LLC; VBL Therapeutics; Verastem, Inc.; and Zentalis Pharmaceuticals.Grant/Research Support from US Oncology Research, LLC.Speaker for AstraZeneca; Clovis Oncology; Eisai Inc.; F. Hoffmann-La Roche Ltd./Genentech, Inc.; Merck & Co., Inc.; and TESARO, Inc./GlaxoSmithKline.Faculty/PlannerAna Oaknin, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Agenus Inc.; AstraZeneca; Clovis Oncology; Corcept Therapeutics; Deciphera Pharmaceuticals; Eisai Co., Ltd.; EMD Serono; Exelisis, Inc.; F. Hoffmann-La Roche; Genmab A/S; GlaxoSmithKline; ImmunoGen, Inc.; iTeos Therapeutics; Merck Sharp & Dohme de Espana SA; Mersana Therapeutics; Novocure GmbH; OncXerna Therapeutics, Inc.; Pharma Mar SA; Regeneron Pharmaceuticals Inc.; Seagen, Inc.; Shattuck Labs, Inc.; and Sutro Biopharma, Inc.Grant/Research Support from AbbVie Deutschland; Advaxis Inc.; Aeterna Zentaris; Amgen Inc.; Aprea Therapeutics AB; Bristol Myers Squibb; Clovis Oncology; Eisai Co., Ltd.; F. Hoffmann-La Roche; ImmunoGen, Inc.; Merck Sharp & Dohme de Espana SA; Millennium Pharmaceuticals Inc.; Pharma Mar SA; Regeneron Pharmaceuticals Inc; and Tesaro.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

phd speaker patients md llc consultants pfizer advisor monk implementation astrazeneca abcs practical tips medical education cervical expert insights facs genentech elevar ovarian glaxosmithkline bristol myers squibb adcs planning committee endometrial cancer accreditation council daiichi sankyo seagen gynecologic cancers myriad genetics emd serono pvi genmab continuing medical education accme bayer corporation pharmacy education acpe eisai inc merck sharp dohme practice aids eisai co hoffmann la roche ltd peerview institute tesaro reviewer disclosuresplanners grant research support disclosure policyall karyopharm sutro biopharma iteos therapeutics cme moc aapa ipce bradley j monk

Bradley J. Monk, MD, FACS, FACOG - The ABCs of ADCs for Gynecologic Cancer: Expert Insights on Effective Implementation and Practical Tips for Use in Patients With Cervical, Ovarian, or Endometrial Cancer

PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Audio Podcast

Play Episode Listen Later Dec 13, 2023 40:44

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/BVX865. CME/MOC/AAPA/IPCE credit will be available until December 10, 2024.The ABCs of ADCs for Gynecologic Cancer: Expert Insights on Effective Implementation and Practical Tips for Use in Patients With Cervical, Ovarian, or Endometrial Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., Eisai Inc., and Seagen and Genmab.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBradley J. Monk, MD, FACS, FACOG, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Acrivon Therapeutics; Adaptimmune Therapeutics plc.; Agenus Inc.; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; AstraZeneca; Bayer Corporation; Clovis Oncology; Eisai Inc.; Elevar, LLC; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd./Genentech, Inc.; Genmab A/S/Seagen Inc.; The GOG Foundation Inc; Gradalis, Inc.; ImmunoGen, Inc.; Iovance Biotherapeutics, Inc.; Jiangsu Hengrui Pharmaceuticals Co., Ltd.; Karyopharm; Laekna Therapeutics; Merck & Co., Inc.; Mersana Therapeutics; Myriad Genetics, Inc.; Novartis Pharmaceuticals Corporation; Novocure GmbH; OncoC4, Inc.; Panavance Therapeutics Inc.; Pfizer; Pieris Pharmaceuticals, Inc.; Puma Biotechnology, Inc.; Regeneron Pharmaceuticals Inc.; Sorrento Therapeutics, Inc.; TESARO, Inc./GlaxoSmithKline; US Oncology Research, LLC; VBL Therapeutics; Verastem, Inc.; and Zentalis Pharmaceuticals.Grant/Research Support from US Oncology Research, LLC.Speaker for AstraZeneca; Clovis Oncology; Eisai Inc.; F. Hoffmann-La Roche Ltd./Genentech, Inc.; Merck & Co., Inc.; and TESARO, Inc./GlaxoSmithKline.Faculty/PlannerAna Oaknin, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Agenus Inc.; AstraZeneca; Clovis Oncology; Corcept Therapeutics; Deciphera Pharmaceuticals; Eisai Co., Ltd.; EMD Serono; Exelisis, Inc.; F. Hoffmann-La Roche; Genmab A/S; GlaxoSmithKline; ImmunoGen, Inc.; iTeos Therapeutics; Merck Sharp & Dohme de Espana SA; Mersana Therapeutics; Novocure GmbH; OncXerna Therapeutics, Inc.; Pharma Mar SA; Regeneron Pharmaceuticals Inc.; Seagen, Inc.; Shattuck Labs, Inc.; and Sutro Biopharma, Inc.Grant/Research Support from AbbVie Deutschland; Advaxis Inc.; Aeterna Zentaris; Amgen Inc.; Aprea Therapeutics AB; Bristol Myers Squibb; Clovis Oncology; Eisai Co., Ltd.; F. Hoffmann-La Roche; ImmunoGen, Inc.; Merck Sharp & Dohme de Espana SA; Millennium Pharmaceuticals Inc.; Pharma Mar SA; Regeneron Pharmaceuticals Inc; and Tesaro.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

phd speaker patients md llc consultants pfizer advisor monk implementation astrazeneca abcs practical tips medical education cervical expert insights facs genentech elevar ovarian glaxosmithkline bristol myers squibb adcs planning committee endometrial cancer accreditation council daiichi sankyo seagen gynecologic cancers myriad genetics emd serono pvi genmab continuing medical education accme bayer corporation pharmacy education acpe eisai inc merck sharp dohme practice aids eisai co hoffmann la roche ltd peerview institute tesaro reviewer disclosuresplanners grant research support disclosure policyall karyopharm sutro biopharma iteos therapeutics cme moc aapa ipce bradley j monk

Bradley J. Monk, MD, FACS, FACOG - The ABCs of ADCs for Gynecologic Cancer: Expert Insights on Effective Implementation and Practical Tips for Use in Patients With Cervical, Ovarian, or Endometrial Cancer

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Dec 13, 2023 40:36

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/BVX865. CME/MOC/AAPA/IPCE credit will be available until December 10, 2024.The ABCs of ADCs for Gynecologic Cancer: Expert Insights on Effective Implementation and Practical Tips for Use in Patients With Cervical, Ovarian, or Endometrial Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., Eisai Inc., and Seagen and Genmab.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerBradley J. Monk, MD, FACS, FACOG, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Acrivon Therapeutics; Adaptimmune Therapeutics plc.; Agenus Inc.; Akeso Biopharma Co., Ltd.; Amgen Inc.; Aravive; AstraZeneca; Bayer Corporation; Clovis Oncology; Eisai Inc.; Elevar, LLC; EMD Serono, Inc.; F. Hoffmann-La Roche Ltd./Genentech, Inc.; Genmab A/S/Seagen Inc.; The GOG Foundation Inc; Gradalis, Inc.; ImmunoGen, Inc.; Iovance Biotherapeutics, Inc.; Jiangsu Hengrui Pharmaceuticals Co., Ltd.; Karyopharm; Laekna Therapeutics; Merck & Co., Inc.; Mersana Therapeutics; Myriad Genetics, Inc.; Novartis Pharmaceuticals Corporation; Novocure GmbH; OncoC4, Inc.; Panavance Therapeutics Inc.; Pfizer; Pieris Pharmaceuticals, Inc.; Puma Biotechnology, Inc.; Regeneron Pharmaceuticals Inc.; Sorrento Therapeutics, Inc.; TESARO, Inc./GlaxoSmithKline; US Oncology Research, LLC; VBL Therapeutics; Verastem, Inc.; and Zentalis Pharmaceuticals.Grant/Research Support from US Oncology Research, LLC.Speaker for AstraZeneca; Clovis Oncology; Eisai Inc.; F. Hoffmann-La Roche Ltd./Genentech, Inc.; Merck & Co., Inc.; and TESARO, Inc./GlaxoSmithKline.Faculty/PlannerAna Oaknin, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Agenus Inc.; AstraZeneca; Clovis Oncology; Corcept Therapeutics; Deciphera Pharmaceuticals; Eisai Co., Ltd.; EMD Serono; Exelisis, Inc.; F. Hoffmann-La Roche; Genmab A/S; GlaxoSmithKline; ImmunoGen, Inc.; iTeos Therapeutics; Merck Sharp & Dohme de Espana SA; Mersana Therapeutics; Novocure GmbH; OncXerna Therapeutics, Inc.; Pharma Mar SA; Regeneron Pharmaceuticals Inc.; Seagen, Inc.; Shattuck Labs, Inc.; and Sutro Biopharma, Inc.Grant/Research Support from AbbVie Deutschland; Advaxis Inc.; Aeterna Zentaris; Amgen Inc.; Aprea Therapeutics AB; Bristol Myers Squibb; Clovis Oncology; Eisai Co., Ltd.; F. Hoffmann-La Roche; ImmunoGen, Inc.; Merck Sharp & Dohme de Espana SA; Millennium Pharmaceuticals Inc.; Pharma Mar SA; Regeneron Pharmaceuticals Inc; and Tesaro.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

phd speaker patients md llc consultants pfizer advisor monk implementation astrazeneca abcs practical tips medical education cervical expert insights facs genentech elevar ovarian glaxosmithkline bristol myers squibb adcs planning committee endometrial cancer accreditation council daiichi sankyo seagen gynecologic cancers myriad genetics emd serono pvi genmab continuing medical education accme bayer corporation pharmacy education acpe eisai inc merck sharp dohme practice aids eisai co hoffmann la roche ltd peerview institute tesaro reviewer disclosuresplanners grant research support disclosure policyall karyopharm sutro biopharma iteos therapeutics cme moc aapa ipce bradley j monk

Paolo Tarantino, MD - Revolutionizing Solid Tumor Treatment, Unleashing the Potential of Antibody–Drug Conjugates: How to Make the Most of the Latest Clinical Evidence to Enhance Patient Care

Play Episode Listen Later Nov 24, 2023 71:23

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/JTS865. CME/MOC/AAPA credit will be available until November 13, 2024.Revolutionizing Solid Tumor Treatment, Unleashing the Potential of Antibody–Drug Conjugates: How to Make the Most of the Latest Clinical Evidence to Enhance Patient Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Speaker for AstraZeneca; Daiichi Sankyo, Inc.; and F. Hoffmann-La Roche Ltd/Genentech, Inc.Faculty/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, lnc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biophanna Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, lnc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer lngelheim Pharmaceuticals, lnc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serano, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; lmmunoGen, Inc.; lmmunomedics, Inc.; lncyte; Infinity Pharmaceuticals, Inc.; lnvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, lnc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; Medlmmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove lnc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr lmmunotherapeutics; Plexxikon; Radius Health, lnc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen lnc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, lnc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; Taplmmune lnc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks (all paid to institution).Faculty/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck and Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck and Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Faculty/PlannerAntonio Passaro, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Daiichi Sankyo, Inc.; GSK; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Janssen Global Services, LLC.; Lilly; Merck Sharp and Dohme; Mundipharma International; Novartis AG; Pfizer; and Takeda Pharmaceutical Company Limited.Grant/Research Support from ArriVent Biopharma; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Janssen Global Services, LLC.; Lilly; Merck Serono; Merck Sharp and Dohme; Mirati Therapeutics, Inc.; Pfizer; and RMC Pharmaceutical Solutions Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

phd speaker team defense patients md llc treatments consultants survival cycle drug quentin tarantino solid pfizer advisor clinical unleashing enhance revolutionizing astrazeneca paolo tumors merck antibodies pharmaceuticals patient care medical education gsk genentech national cancer institute glaxosmithkline abbvie bristol myers squibb dana farber cancer institute gilead sciences planning committee accreditation council curis janssen pharmaceuticals daiichi sankyo boehringer seagen antibody drug conjugates pvi continuing medical education accme abbvie inc dohme pharmamar bayer corporation pharmacy education acpe janjigian merck sharp mirati therapeutics astellas pharma inc peerview institute merck serono compugen tesaro hoffmann la roche ltd reviewer disclosuresplanners grant research support disclosure policyall seagen inc arvinas takeda pharmaceutical company limited inspirna iteos therapeutics karyopharm sutro biopharma bayer healthcare pharmaceuticals cme moc aapa arcus biosciences g1 therapeutics millennium pharmaceuticals fred's team boehringer ingelheim international gmbh daiichi sankyo inc sermonix pharmaceuticals syros pharmaceuticals stock shareholder effector therapeutics imugene limited acerta pharma transcenta holding rgenix inc askgene pharma basilea pharmaceutica ltd mersana therapeutics inc zymeworks inc hoffmann la roche ltd genentech

Paolo Tarantino, MD - Revolutionizing Solid Tumor Treatment, Unleashing the Potential of Antibody–Drug Conjugates: How to Make the Most of the Latest Clinical Evidence to Enhance Patient Care

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast

Play Episode Listen Later Nov 24, 2023 71:28

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/JTS865. CME/MOC/AAPA credit will be available until November 13, 2024.Revolutionizing Solid Tumor Treatment, Unleashing the Potential of Antibody–Drug Conjugates: How to Make the Most of the Latest Clinical Evidence to Enhance Patient Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Speaker for AstraZeneca; Daiichi Sankyo, Inc.; and F. Hoffmann-La Roche Ltd/Genentech, Inc.Faculty/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, lnc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biophanna Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, lnc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer lngelheim Pharmaceuticals, lnc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serano, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; lmmunoGen, Inc.; lmmunomedics, Inc.; lncyte; Infinity Pharmaceuticals, Inc.; lnvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, lnc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; Medlmmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove lnc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr lmmunotherapeutics; Plexxikon; Radius Health, lnc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen lnc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, lnc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; Taplmmune lnc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks (all paid to institution).Faculty/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck and Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck and Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Faculty/PlannerAntonio Passaro, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Daiichi Sankyo, Inc.; GSK; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Janssen Global Services, LLC.; Lilly; Merck Sharp and Dohme; Mundipharma International; Novartis AG; Pfizer; and Takeda Pharmaceutical Company Limited.Grant/Research Support from ArriVent Biopharma; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Janssen Global Services, LLC.; Lilly; Merck Serono; Merck Sharp and Dohme; Mirati Therapeutics, Inc.; Pfizer; and RMC Pharmaceutical Solutions Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

phd speaker team defense patients md llc treatments consultants survival cycle drug quentin tarantino solid pfizer advisor clinical unleashing enhance revolutionizing astrazeneca paolo tumors merck antibodies pharmaceuticals patient care medical education gsk genentech national cancer institute glaxosmithkline abbvie bristol myers squibb dana farber cancer institute gilead sciences planning committee accreditation council curis janssen pharmaceuticals daiichi sankyo boehringer seagen antibody drug conjugates pvi continuing medical education accme abbvie inc dohme pharmamar bayer corporation pharmacy education acpe janjigian merck sharp mirati therapeutics astellas pharma inc peerview institute merck serono compugen tesaro hoffmann la roche ltd reviewer disclosuresplanners grant research support disclosure policyall seagen inc arvinas takeda pharmaceutical company limited inspirna iteos therapeutics karyopharm sutro biopharma bayer healthcare pharmaceuticals cme moc aapa arcus biosciences g1 therapeutics millennium pharmaceuticals fred's team boehringer ingelheim international gmbh daiichi sankyo inc sermonix pharmaceuticals syros pharmaceuticals stock shareholder effector therapeutics imugene limited acerta pharma transcenta holding rgenix inc askgene pharma basilea pharmaceutica ltd mersana therapeutics inc zymeworks inc hoffmann la roche ltd genentech

Paolo Tarantino, MD - Revolutionizing Solid Tumor Treatment, Unleashing the Potential of Antibody–Drug Conjugates: How to Make the Most of the Latest Clinical Evidence to Enhance Patient Care

PeerView Oncology & Hematology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Nov 24, 2023 71:23

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/JTS865. CME/MOC/AAPA credit will be available until November 13, 2024.Revolutionizing Solid Tumor Treatment, Unleashing the Potential of Antibody–Drug Conjugates: How to Make the Most of the Latest Clinical Evidence to Enhance Patient Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Speaker for AstraZeneca; Daiichi Sankyo, Inc.; and F. Hoffmann-La Roche Ltd/Genentech, Inc.Faculty/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, lnc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biophanna Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, lnc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer lngelheim Pharmaceuticals, lnc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serano, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; lmmunoGen, Inc.; lmmunomedics, Inc.; lncyte; Infinity Pharmaceuticals, Inc.; lnvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, lnc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; Medlmmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove lnc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr lmmunotherapeutics; Plexxikon; Radius Health, lnc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen lnc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, lnc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; Taplmmune lnc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks (all paid to institution).Faculty/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck and Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck and Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Faculty/PlannerAntonio Passaro, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Daiichi Sankyo, Inc.; GSK; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Janssen Global Services, LLC.; Lilly; Merck Sharp and Dohme; Mundipharma International; Novartis AG; Pfizer; and Takeda Pharmaceutical Company Limited.Grant/Research Support from ArriVent Biopharma; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Janssen Global Services, LLC.; Lilly; Merck Serono; Merck Sharp and Dohme; Mirati Therapeutics, Inc.; Pfizer; and RMC Pharmaceutical Solutions Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

phd speaker team defense patients md llc treatments consultants survival cycle drug quentin tarantino solid pfizer advisor clinical unleashing enhance revolutionizing astrazeneca paolo tumors merck antibodies pharmaceuticals patient care medical education gsk genentech national cancer institute glaxosmithkline abbvie bristol myers squibb dana farber cancer institute gilead sciences planning committee accreditation council curis janssen pharmaceuticals daiichi sankyo boehringer seagen antibody drug conjugates pvi continuing medical education accme abbvie inc dohme pharmamar bayer corporation pharmacy education acpe janjigian merck sharp mirati therapeutics astellas pharma inc peerview institute merck serono compugen tesaro hoffmann la roche ltd reviewer disclosuresplanners grant research support disclosure policyall seagen inc arvinas takeda pharmaceutical company limited inspirna iteos therapeutics karyopharm sutro biopharma bayer healthcare pharmaceuticals cme moc aapa arcus biosciences g1 therapeutics millennium pharmaceuticals fred's team boehringer ingelheim international gmbh daiichi sankyo inc sermonix pharmaceuticals syros pharmaceuticals stock shareholder effector therapeutics imugene limited acerta pharma transcenta holding rgenix inc askgene pharma basilea pharmaceutica ltd mersana therapeutics inc zymeworks inc hoffmann la roche ltd genentech

Paolo Tarantino, MD - Revolutionizing Solid Tumor Treatment, Unleashing the Potential of Antibody–Drug Conjugates: How to Make the Most of the Latest Clinical Evidence to Enhance Patient Care

Play Episode Listen Later Nov 24, 2023 71:28

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, slides, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at PeerView.com/JTS865. CME/MOC/AAPA credit will be available until November 13, 2024.Revolutionizing Solid Tumor Treatment, Unleashing the Potential of Antibody–Drug Conjugates: How to Make the Most of the Latest Clinical Evidence to Enhance Patient Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca, Daiichi Sankyo, Inc., and Gilead Sciences, Inc.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerPaolo Tarantino, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; and Lilly.Grant/Research Support from AstraZeneca.Speaker for AstraZeneca; Daiichi Sankyo, Inc.; and F. Hoffmann-La Roche Ltd/Genentech, Inc.Faculty/PlannerErika Hamilton, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcus Biosciences, Inc.; Arvinas, Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Deciphera Pharmaceuticals, lnc.; Ellipses Pharma; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Greenwich LifeSciences, Inc.; iTeos Therapeutics; Janssen Pharmaceuticals, Inc.; Lilly; Loxo Oncology; Mersana Therapeutics; Novartis Pharmaceuticals Corporation; Orum Therapeutics; Pfizer; Relay Therapeutics; Seagen Inc.; and Verascity Science (all paid to institution).Grant/Research Support from AbbVie Inc.; Accutar Biotechnology Inc; Acerta Pharma; ADC Therapeutics SA; Akeso Biophanna Co., Ltd.; Amgen Inc.; Aravive; Artios Pharma; Arvinas, Inc.; AstraZeneca; AtlasMedx, Inc.; BeiGene, lnc.; Black Diamond Therapeutics, Inc.; Bliss Biopharmaceutical (Hangzhou) Co., Ltd.; Boehringer lngelheim Pharmaceuticals, lnc.; Cascadian Therapeutics; Clovis Oncology; Compugen; Cullinan Oncology, Inc.; Curis, Inc.; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; Dana-Farber Cancer Institute; Dantari; Deciphera Pharmaceuticals, Inc.; Duality Biologics; eFFECTOR Therapeutics, Inc.; Ellipses Pharma; Elucida Oncology, Inc.; EMD Serano, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; FUJIFILM Pharmaceuticals U.S.A., Inc.; G1 Therapeutics, Inc.; H3 Biomedicine Inc.; Harpoon Therapeutics; HUTCHMED (China) Limited; lmmunoGen, Inc.; lmmunomedics, Inc.; lncyte; Infinity Pharmaceuticals, Inc.; lnvestisBio; Jacobio Pharmaceuticals Group Co., Ltd.; K-Group Beta, lnc.; Karyopharm; Lilly; Loxo Oncology; Lycera; MabSpace Biosciences Co., Ltd.; MacroGenics, Inc.; Medlmmune, LLC; Mersana Therapeutics; Merus; Millennium Pharmaceuticals, Inc.; Molecular Templates, Inc.; Novartis Pharmaceuticals Corporation; Nucana; Olema Oncology; OncoMed Pharmaceuticals, Inc.; Onconova Therapeutics; Oncothyreon; ORIC Pharmaceuticals, Inc.; Orinove lnc.; Pfizer; PharmaMar; Pieris Pharmaceuticals, Inc.; Pionyr lmmunotherapeutics; Plexxikon; Radius Health, lnc.; Regeneron Pharmaceuticals Inc.; Relay Therapeutics; Repertoire Immune Medicines; Rgenix Inc.; Seagen lnc.; Sermonix Pharmaceuticals; Shattuck Labs Inc.; Stemcentrx, Inc.; Sutro Biopharma, lnc.; Syndax; Syros Pharmaceuticals, Inc.; Taiho Oncology, Inc.; Taplmmune lnc; TESARO, Inc.; Tolmar Pharmaceuticals, Inc.; Torque Therapeutics, Inc.; Treadwell Therapeutics; Verastem, Inc.; Vincerx Pharma; zenithepigenetics; and Zymeworks (all paid to institution).Faculty/PlannerYelena Y. Janjigian*, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie, Inc.; AmerisourceBergen; Arcus Biosciences; AskGene Pharma, Inc.; Astellas Pharma Inc.; AstraZeneca; Basilea Pharmaceutica Ltd.; Bayer Corporation; Bristol Myers Squibb; Daiichi Sankyo Inc.; GlaxoSmithKline; Guardant Health; Imugene Limited; Inspirna, Inc.; Lilly; Merck and Co., Inc.; Merck Serono; Mersana Therapeutics Inc.; Pfizer; Rgenix Inc.; Seagen Inc.; Silverback Therapeutics (ARS Pharmaceuticals) and Zymeworks Inc.Grant/Research Support from Arcus Biosciences; AstraZeneca; Bayer HealthCare Pharmaceuticals, Inc.; Bristol Myers Squibb; Cycle for Survival; Fred's Team; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Inspirna, Inc.; Lilly; Merck and Co., Inc.; National Cancer Institute; Transcenta Holding; and U.S. Department of Defense.Stock Shareholder in Inspirna, Inc.Faculty/PlannerAntonio Passaro, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Daiichi Sankyo, Inc.; GSK; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Janssen Global Services, LLC.; Lilly; Merck Sharp and Dohme; Mundipharma International; Novartis AG; Pfizer; and Takeda Pharmaceutical Company Limited.Grant/Research Support from ArriVent Biopharma; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Daiichi Sankyo, Inc.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Janssen Global Services, LLC.; Lilly; Merck Serono; Merck Sharp and Dohme; Mirati Therapeutics, Inc.; Pfizer; and RMC Pharmaceutical Solutions Inc.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

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Changing the Gut Microbiome to Improve the Efficacy of Immunotherapy

Play Episode Listen Later Oct 12, 2023 28:25

Drs. Diwakar Davar and Ben Boursi discuss the role of the gut microbiome in the outcome of cancer immunotherapy and the prevention of immunotherapy-related adverse events, as well as compelling research on nutritional interventions to improve response to immune checkpoint inhibitors. TRANSCRIPT Dr. Diwakar Davar: Hello, and welcome to the ASCO Daily News Podcast. I'm your guest host, Dr. Diwakar Davar. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. Researchers have shown that microorganisms in the gut can impact the effectiveness of immunogenic chemotherapy for patients with cancer. Although microbial therapies for cancer are still at a very early stage of clinical development, compelling research in recent years has shown that changing the gut microbiome can help improve outcomes in patients receiving treatments for cancer enduring immune checkpoint inhibition. My guest today is Dr. Ben Boursi, a GI medical oncologist at the Sheba Medical Center at Tel Aviv University in Israel. Dr. Boursi is also an adjunct professor at the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania. He joins me today to discuss his pivotal research on the role of the gut microbiome in mediating its effects on immunotherapy. And again, I want to highlight that we're recording this on October 9th, and as you may well know, many recent events over the last couple of days have happened in Israel, and so Dr. Boursi has joined us at a very difficult time. So, we're very grateful for him taking time out of his suddenly very busy schedule to join us at a time that is fraught for all. You'll find our disclosures in the transcript of this episode. You'll also find the disclosures of all guests on the podcast at asco.org/DNpod. Ben, it's great to have you on the podcast today. Thank you for being here at such a difficult time, sharing what will, I think, be a great episode. Dr. Ben Boursi: Thanks for having me, Diwakar. Dr. Diwakar Davar: Ben, the gut microbiome and its role in terms of mediating effects and side effects of cancer immunotherapy has gotten a lot of interest recently. You've done some fundamental work in this space. Why don't you briefly summarize for the audience, firstly, what is the gut microbiome and what are the major themes in relation to cancer immunotherapy? Dr. Ben Boursi: Well, the microbiome is the ecosystem of microorganisms, bacteria, phages, fungi, that are crucial for immunologic, metabolic and hormonal homeostasis of the host. In the last decade, we began to understand the central role of the gut and tumor microbiome in tumorigenesis, metastasis, treatment efficacy and toxicities, and in 2022, polymorphic microbiomes became one of the hallmarks of cancer, in addition to previous hallmarks that focused mainly at the cellular/genetic levels. The initial studies in mice models showed that therapeutic efficacy of immunotherapy depends on both the presence and composition of the microbiota (In germ-free or antibiotic treated mice, immunotherapy is ineffective), and following these studies, three observational studies in human patients showed that the gut microbiome can predict response to immunotherapy and that response to immunotherapy could be transferred to germ-free mice by fecal microbiota transplantation (FMT) from responding patients. These studies helped us to define three main research questions regarding the possible role of microbial modulation in cancer treatment. First, can microbial modulation overcome resistance to immunotherapy, both primary and secondary resistance? And this question was the focus of the initial proof of concept studies. Second, can microbial modulation improve response to immunotherapy in treatment-naive patients? And third, can microbial modulation prevent or treat immune related adverse events? The initial positive results of clinical trials also led to additional questions. For example, can microbial modulation induce anti-tumor immune response even in non-immunogenic tumors? And it is important to note that there are many ways to modulate the microbiota, but so far, the only reliable way that showed positive results is fecal microbiota transplantation that allows the transfer of the entire microbiota both in terms of composition and relative abundance. Dr. Diwakar Davar: That's great. Essentially with the trials that I think the data sets that you're referencing of course, are papers by Jennifer Wargo, Thomas Gajewski, and Lawrence Zitvogel, looking at the role of gut microbiota in several different cancers, primarily immune checkpoint sensitive tumors such as melanoma, non-small cell lung cancer and kidney cancer. And then the work from several different groups showing that essentially proof of concept experiments can be done to try to change this, certainly preclinically, and now we know that that can be done clinically. So, I guess the failure rates of immunotherapy in some patients are quite high. And we know that the microbial composition can change the likelihood to respond to immunotherapy based on all these trials. And actually, even going back to 2015, we had two seminal papers that looked at the role of CTLA-4 blockade as well. But subsequently, many years after that, 7 years after 2015, and certainly 3 years after 2018, when the three observational PD-1 papers were published, there were 2 pivotal trials in PD-1 advanced or refractory melanoma. They demonstrated that changing the gut microbiome can reprogram the immune system to attack tumors. So, there were 2 separate trials, both published the same issue of Science. One trial was led by your group at Sheba, and another one's led by us, the University of Pittsburgh. Why don't you summarize both studies for our audience. Dr. Ben Boursi: So, both studies were Phase I clinical trials of FMT in metastatic melanoma patients who failed immunotherapy. Recipients were metastatic melanoma patients that progressed on at least one line of anti PD-1 and in BRAF mutated patients, BRAF inhibitors as well. Donors in the Sheba study were metastatic melanoma patients with durable complete responses to immunotherapy for at least one year, and in the Pittsburgh study, you also included patients with durable partial responses of more than two years as donors. It is important to note that each fecal transplant in both studies was composed of a single donor. Prior to transplantation, we performed a microbiome depletion phase using a combination of two antibiotics, vancomycin and neomycin. The goal of this phase was to assist in engraftment (by avoiding colonization-resistance by recipient bacteria) and to “reset” the immune system, which may remind some people of the logic behind bone marrow transplantation. In the Pittsburgh study, there was no bacterial eradication with antibiotics, mainly because of studies showing that response to immunotherapy is lower following antibiotic treatment. Both studies performed FMT through colonoscopy. At Sheba, we also performed maintenance FMT using capsules in order to keep the donor's microbial composition. After the initial FMT, both studies reintroduced the same immunotherapy in which the patient progressed in the past. Clinically, we have seen a 30% response rate with durable, complete and partial responses, and in the Pittsburgh study, there was a 20% response rate and 40% disease control rate. Both studies showed following FMT, immune response in the gut and in the tumor, and tumors that were immune deserts prior to FMT became infiltrated with lymphocytes. Interestingly, in our study, there were no moderate to severe immune related adverse events following FMT and reintroduction of immunotherapy. And this is despite the fact that five of the patients had significant side effects during previous rounds of the same immunotherapy. Dr. Diwakar Davar: So essentially, in these very early proof of concept studies, what I think is pretty remarkable is that obviously the sample sizes were very small, but remarkably, patients that appeared to respond, responded in a setting in which they were not expected to respond. So, the probability of a patient responding to attempt at giving PD-1 in patients who were PD-1 relapse refractory is on the order of about 7%, based on an FDA analysis by Viva et al. And here, two separate studies, two independent studies, investigators had not known that each paper was being published, remarkably similar results clearly demonstrating that this is perhaps one of the best pieces of evidence to suggest that microbiome modulation may actually truly be effective in reversing PD-1 refractoriness. More recently, our colleague Dr. Bertrand Routy at University of Montreal has done a proof of concept trial in evaluating the use of healthy donor fecal microbiota transplant in addition to anti PD-1 monotherapy in PD-1 naive metastatic melanoma. In this study, published in Nature Medicine a few weeks ago, his group reported an objective response rate of 65%. What are your thoughts about this study? And specifically, what are your thoughts about some of the pharmacodynamic and translational results that were demonstrated? Dr. Ben Boursi: This is a very interesting question, because in both the Sheba and the University of Pittsburgh studies we chose responding patients as donors. We thought that by using these patients, we provide beneficial bacteria that enhance responses to immunotherapy through several mechanisms (molecular mimicry, immunomodulatory bacterial metabolites, modulation of immune checkpoint expression, and much more), and here in the Routy paper, the researchers used FMT from healthy donors without any selection for specific beneficial bacteria, and they demonstrated a similar effect on overall response rate. So maybe FMT works actually through reducing colonization by deleterious bacteria? Another question that we should ask is whether we need to choose donors differently when we use microbial modulation in treatment resistant patients compared to treatment-naive patients? Moreover, a previous meta-analysis of FMT studies across indications that was conducted by the group of Dr. Nicola Segata, demonstrated that recipients with better engraftment were more likely to experience clinical benefit, and that increased engraftment was mainly observed in individuals receiving FMTs through multiple routes, colonoscopy and capsules, as well as recipients that received antibiotics prior to FMT. But in Routy's trial, they not only used healthy donors, they performed bacterial cleansing only prior to FMT instead of bacterial eradication with antibiotics, and used FMTs through colonoscopy only, and they didn't give maintenance FMT. Of course, such an approach is much more feasible in the clinical setting and is relevant for designing future clinical trials. Dr. Diwakar Davar: So, many differences, relatively few similarities, but I guess one interesting point is that of engraftment, which is that in your paper, our paper, and certainly in Bertrand's paper, it is very interesting that engraftment appears to be a key pharmacodynamic biomarker of microbiome modulation. And certainly, the analogy that you used earlier, which is that it's very similar to what happens in a stem cell transplant, which is that if there's no take, there's probably not going to be any effect. So that's very interesting that engraftment is emerging as a key PD biomarker of essentially the success of any kind of microbiome modulation across multiple different settings. Now, we've heard of certainly defined microbial consortia, of cultivated species, as an alternative gut microbiome modulation strategy that balances the benefits of the ecological complexity of FMT with the scalability and practicality of probiotics. Do you think we are ready to design consortia? Dr. Ben Boursi: So to date there are several probiotics that use a single bacteria and several microbial consortia that were evaluated in clinical trials, and as you mentioned, they may offer more tractable solutions for widespread clinical use. If we begin with the single bacteria probiotics, two phase 2 clinical trials found that administration of the butyrate producing probiotic clostridium butyricum 588 (CBM588) to immunotherapy naive patients with metastatic renal cell carcinoma led to markedly better immunotherapy responses, although the probiotic had a minimal effect on the composition of the microbiota, and the control arm of the trial responded worse than expected. In addition, in preclinical studies, probiotic strains of lactobacillus and bifidobacterium have been shown to enhance immune control of transplanted tumors and to augment anti PD-1 activity. However, a clinical trial in patients with metastatic melanoma found that the use of lactobacillus or bifidobacterium probiotics was associated with reduced microbiota diversity and worse responses to anti PD-1. So here the conclusion is that when we try to design probiotics, we should not focus only on the composition since other factors, such as the relative abundance also matter. Too much of a beneficial bacterial species may potentially be worse than having a balanced and diverse microbiota. For example, a recent study of patients with non-small cell lung cancer receiving immunotherapy found that patients with a detectable Akkermansia muciniphila in their gut microbiota (this is a beneficial bacteria) responded well to treatment, but those with relative abundance of Akkermansia muciniphila greater than 5% responded worse than patients lacking Akkermansia, and this is due to the mucolytic effect of the bacteria. So, the use of rationally designed consortia may be better than a single probiotic strain. And there are currently 3 main microbial consortia that are being evaluated: the SER-401, a bacterial consortium enriched with clostridium, led in a randomized controlled trial to reduced response to immunotherapy compared to placebo control in first line metastatic melanoma patients, potentially due to a confounding effect of a vancomycin pretreatment; MET4 is a 30 bacteria consortium that was shown to be safe and to alter the gut microbiota and serum metabolome of immunotherapy naive patients. Here, the initial study was underpowered to determine the effect on treatment efficacy; And finally, VE800 is an immunotherapy enhancing 11-bacterial consortium that is currently being evaluated in phase 1 and 2 clinical trials, and we are looking forward to see the results with this agent. Dr. Diwakar Davar: So I guess where we are right now is that social design is clearly difficult because of all the reasons you've mentioned. The SER-401 data and the MET4-IO trials certainly give us pause for thought. Certainly, no pharmacodynamic changes that were seen with SER-401, MET4-IO did result in pharmacodynamic shifts metagenomically, but neither trial was positive. And certainly, the VE800 trial, which has been ongoing now for several years, and the lack of publicly reported data certainly doesn't suggest that there's a huge efficacy signal. So consortias, at least at this point, certainly do not appear to be having a significant effect, though we don't know what might happen in the future. Data from multiple groups has shown that gut microbial composition influences the development of immune related adverse events (irAEs) in both PD-1 and combination PD-1 and CTLA-4 treated patients. Unsurprisingly, as a result, there have been attempts made at evaluating the role of fecal microbiota transplants to treat refractory immune related adverse events and very specifically immune checkpoint associated colitis or IMC. So, Dr. Yinghong Wang, who is the chair of the Immunotherapy Toxicity Working Group at the University of Texas MD Anderson Cancer Center has been very prominent in this space, and in a recent paper published in Science Translational Medicine, which is a follow up paper to her early work in Nature Medicine, she reported that HDFMT, healthy donor fecal transplantation, was very efficacious in feeding early refractory immune checkpoint colitis. So, what are your thoughts on this approach and how important is this space and where else might it be efficacious? Dr. Ben Boursi: When I talked about the Sheba clinical study, I mentioned the possible role for microbiota modulation in the prevention of immunotherapy related adverse events in general, not only colitis. But the study by Dr. Yinghong showed that FMT can actually treat immune-related colitis refractory to steroids and anti-TNF. Now, this approach is probably relevant not only for immune related colitis, but also to other immune related adverse events. We can define certain bacterial species that may be associated with different immune related events. For example, streptococci can be associated with immune related arthritis. And maybe in the future we won't need to use FMT, but we will rather be able to target these specific immunogenic strains by narrow spectrum antibiotics or phages. The main challenge would be to develop microbiotic targeting interventions that reduce immune related adverse events without compromising therapeutic efficacy. Now, is microbial modulation relevant only for toxicity from immune checkpoint inhibitors? So, the answer is ‘no'. We know mainly from animal models of hematopoietic cell transplantation, CAR T, and immune agonist antibodies that antibiotic-treated or germ-free mice have markedly reduced immunotoxicity, such as graft versus host disease, cytokine release syndromes, and more. It is also worth mentioning that microbial modulation is relevant not only for reducing toxicity from immunotherapy, but also from chemotherapy and other anticancer modalities. And the best example is the gastrointestinal toxicity of irinotecan that is mediated by the bacterial beta-glucuronidase. And here the targeting may even be a bit less complex. Dr. Diwakar Davar: So, what we take away from that is that starting with actually your paper originally, and papers to be produced, immune-related adverse events can be prevented using microbiome modulation with FMT, and Dr. Wang's data suggesting that eventually FMT can be used to eradicate highly refractive colitis, again, this is important to keep in mind that this approach is not yet FDA-approved. It's being done under IND. It's not currently something that is a certain standard of care. One interesting area of drug development is that there's a French microbiome company named MaaT Pharma where they have an agent that is a very interestingly a pooled microbiome product from multiple different donors. Again, the trials in both Israel and Pittsburgh used individual donors. This is a pooled donor construct. The lead candidate is actually graft versus host disease. The trial is the ARES trial, A-R-E-S, as in the Roman god of war. This trial is actually ongoing in Europe, and I believe there's some effort to try to see whether or not it's going to be a trial that can be done in the United States as well. So, at this point in time, again, we don't know whether or not there are any developmental approaches from a pharmaceutical company in the United States, but certainly this is definitely an area of interest. So microbial therapies are still relatively early. It's going to be interesting to see how the advanced field of nutritional interventions provide an appealing method for modulating the gut microbiome due to the excellent safety profile, cost effectiveness and noninvasiveness. And certainly, if you are what you eat and your bacteria are what they eat, which goes down to our diet, there's enough rationale to believe that certain nutritional interventions can have an effect via the intermedial gut microbiota modulation. Holistic dietary changes and or supplementation specific nutrients such as prebiotics could therefore be utilized to specifically shape the population of beneficial microbes and shift the immune microbiota landscape. Now, we have seen in data published by several of our colleagues that in patients with cancer, high fiber intake is associated with greater microbial diversity, greater abundance in fiber fermenting microbes such as members of the Ruminococcaceae family, and these are all associated with the response to checkpoint inhibitor therapy. So, what do you think about nutritional interventions? Do you want us to briefly summarize data regarding nutritional data and where it stands in cancer at his time? And can you speculate as to how effective this might be in the context of patients with cancer? Dr. Ben Boursi: So, let's begin with diet. A growing number of clinical and preclinical studies suggest that specific dietary interventions such as a high fiber diet can not only improve response to immune checkpoint blockers, but also reduce immunotoxicity such as graft versus host disease. And there are many other diets that are being tested such as ketogenic diets and intermittent fasting. And the effects of diet may be mediated by both microbiota-dependent and microbiota-independent mechanisms. The limitation of this approach is that changes to the microbiota induced by diet are generally quite variable between patients and can depend on an individual's microbiota prior to intervention. And patient compliance is also a concern, particularly in the very strict diets. Now, regarding high fiber diets, several large cohorts of melanoma patients from the US, Australia, and the Netherlands demonstrated how a high fiber diet modulates the microbiome and results in a better response to immunotherapy, better progression-free survival. Additional studies that were presented at AACR in 2023 showed that high fiber dietary interventions, in which patients received a fiber-enriched diet for six weeks, was feasible and that the high fiber diet resulted in a rapid shift in the gut microbiota toward fiber-responsive short chain fatty acid-producing taxa and a shift of the metabolome, with increase in the short chain fatty acid acetate, Omega-3, Omega-6, polyunsaturated fatty acid, and tryptophan metabolites. Prebiotics can also promote the growth of beneficial microbial species in the gut by providing targeted nutrition. And one example of a prebiotic that was shown to enhance immunotherapy efficacy in mouse models is castalagin, which is isolated from the camu-camu berry. Castalagin directly binds the outer membrane of ruminococci and promotes their growth, which has been shown to increase the CD8-positive T-cell activity and anti-PD-1 efficacy. Now, since prebiotics rely on the presence of beneficial taxa already in the host microbiota, symbiotics, which refers to the administration of the appropriate prebiotic and probiotic together, may prove in the future to be more effective than using either separately. Dr. Diwakar Davar: Certainly, these dietary interventions can be very exciting and certainly we do know of several colleagues who are doing these diet interventions, though compliance with any kind of dietary intervention may be a challenge that decides how effective such an approach is going to be. So microbial therapies in general are still at a relatively early stage of development. And it'll be exciting to see how they advance. What approaches are you excited about? What is on your radar? Dr. Ben Boursi: There are many exciting works that are currently ongoing, and to emphasize just a few: there are many clinical trials in immunogenic tumors, in addition to melanoma, for example, renal cell carcinoma, and non-small cell lung cancer, that also evaluate different modulation protocols. We should remember that one size does not fit all, and different tumors have different microbiomes. We have a project in collaboration with MD Anderson in MSI-high patients with exciting initial results. Another study that was initiated at Sheba is using microbial modulation in order to improve TIL therapy (to overcome resistance to TIL and T-cell exhaustion). There are also studies that try to change the pharmaco-microbiome, for example, to eradicate bacteria that inactivates the chemotherapy agent, gemcitabine, in pancreatic cancer patients. And there are groups that try to identify recipients that will respond to microbial modulation and to generate better donor-recipient matching algorithms. There are already signatures like TOPOSCORE that was presented at ASCO 2023 that try to predict response to immunotherapies through the ratio between harmful and beneficial bacteria. Now, there's also more basic science work, for example, bacterial engineering. There was a wonderful study from the Fischbach group in Stanford that demonstrated how Staphylococcus epidermidis engineered to express melanoma tumor antigens was able to generate a systemic tumor-specific response in mice models when applied topically; functional imaging of the microbiome, for example, FDG uptake in the colon can reflect microbial diversity and response to immunotherapy; works that characterizes other microbiomes such as the urinary and skin microbiomes, and their interaction with the gut microbiome; and studies of the nonbacterial component of the microbiome, mainly phages and fungi. But for me, the most important word should probably be collaboration, because without joining forces internationally, we won't be able to understand the human metaorganism, the variations according to geography, ethnicity, lifestyle, diets, and much more in the microbiome. And this is crucial in order to really understand the complex tumor ecological niche within the human host. Dr. Diwakar Davar: I think one of the key points that you just mentioned is collaboration. That's going to be very, very critical as we move this forward for many reasons, including the unexpected impact of geography upon the composition of the gut microbiome in work that has been published by many groups, but also including ours in a paper that we published about a year ago now. So, Dr. Boursi, thank you for your great work in this area. Thank you for sharing your insights with us today on the ASCO Daily News Podcast. This is a very difficult time for all of you and your colleagues in Israel, and we thank you so much for taking such a great deal of time out of your busy workday to spend some time with us. Dr. Ben Boursi: Thank you very much. Dr. Diwakar Davar: Thank you to all our listeners today. This is a very exciting area. This is an area where we are discovering more every day than we knew just up until the day prior. You will find the links to the studies that were discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take the time to rate, review, and subscribe wherever you get your podcast. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guests' statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers: Dr. Diwakar Davar Dr. Ben Boursi Follow ASCO on social media:   @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn   Disclosures: Dr. Diwakar Davar:    Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences   Consulting or Advisory Role: Instil Bio, Vedanta Biosciences   Consulting or Advisory Role (Immediate family member): Shionogi   Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences   Research Funding (Inst.): Zucero Therapeutics   Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy     Dr. Ben Boursi: No relationships to disclose.

Spotlight on Immunotherapy at ASCO23

Play Episode Listen Later Jun 26, 2023 34:23

Drs. Diwakar Davar and Jason Luke discuss KEYNOTE-716, KEYNOTE-942, RELATIVITY-047, and other key advances in melanoma, including the promise of mRNA vaccines in melanoma and potentially other cancers, as well exciting advances in neoadjuvant therapies across malignancies featured at the 2023 ASCO Annual Meeting. TRANSCRIPT Dr. Diwakar Davar: Hello, and welcome to the ASCO Daily News Podcast. I'm your guest host, Dr. Diwakar Davar. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh Hillman Cancer Center. I'm delighted to have my colleague and good friend Dr. Jason Luke on the podcast today to discuss some practice-changing studies and other advances in immunotherapy that were featured at the 2023 ASCO Annual Meeting. Dr. Luke is an associate professor of medicine, the director of the Cancer Immunotherapy Center, as well as the associate director of clinical research at the University of Pittsburgh's Hillman Cancer Center. You can find both of our disclosures in the transcript of this episode, and disclosures of all guests on the ASCO Daily News Podcast are available on our transcripts at asco.org/DNpod. Jason, there was a lot of exciting data in the immunotherapy space highlighted at the Annual Meeting, and it's great to have you back on the podcast to discuss some of this work. Dr. Jason Luke: Thanks for having me. Dr. Diwakar Davar: So, the abstracts that we had selected have several key themes. We'll be covering some of the early advances in melanoma in the stage 2 and stage 2B/C space with KEYNOTE-716. I think this is a study that you know a little bit about seeing you are the presenting author and the principal investigator for the study, as well as the pivotal KEYNOTE-942 trial. And then going on to themes with using third-generation checkpoints, neoadjuvant therapy in non-small-cell lung cancer, and cutaneous squamous cell carcinoma. But we'll start with KEYNOTE-716. So, this is LBA9505, the study which evaluated pembrolizumab versus placebo as adjuvant therapy in stage 2B and stage 2C melanoma patient population for which historically there was no real effective therapy other than remotely interferon. And these are the final results of the DMFS analysis from this phase 3 trial. So, Jason, what are your thoughts about this, and can you contextualize the results relative to the recent publication? Dr. Jason Luke: Thanks. I think the important point to level set on this was just a few years ago; this was a population of patients that we didn't treat in clinic. In fact, sometimes they weren't even referred to medical oncology for evaluation. And that was despite the fact that we knew from historical data that the risk of melanoma-specific survival, death from melanoma, was just as high for this population of patients as it was for the patients with stage 3 melanoma, where obviously adjuvant immunotherapy has been a standard for quite some time. And so we launched this clinical trial, KEYNOTE-716. It was a global, randomized phase 3 study of almost 1,000 patients, randomizing patients to either get pembrolizumab or placebo. Importantly, these patients being those with deep primary lesions, stage 2B and 2C with negative sentinel lymph node evaluation. People will recall that this study hit its primary endpoint on the first protocol-specified analysis at a year. And what we updated at ASCO this year was the final analysis of distant metastasis-free survival. Obviously, an important secondary endpoint because if patients eventually going to develop metastatic disease and pass away, it's the distant metastasis that we worry about. And what we saw in this trial with a landmark 36-month follow-up median of 39 months was that the benefit was increasing. In other words, the magnitude of the hazard ratio change was increasing over time as would be expected, such that at this analysis there was a 41% reduction in the risk of distant metastasis for patients treated with pembrolizumab versus placebo. And we saw a consistent benefit in the recurrence-free survival also out through that same period of time and importantly no change in the safety summary with of course the adverse event profile of pembrolizumab being what it is and well understood across oncology. So I think these are very important data because they really kind of set the stage for the field. It is now the case that at least discussing adjuvant therapy for patients with stage 2B and 2C is the standard of care; it should be offered to all the patients. Of course, it's always a risk-benefit about whether or not patients want to pursue adjuvant therapy versus consideration of treatment at the time of recurrence. But in my clinic at least, many patients do prefer to try to eliminate the possibility of recurrence and distant metastasis as much as possible. So I think these are very important data because they really level set the field for what to expect in this population of patients and then they also start to set the table for what's going to come after this. And that's going to be sort of the next step in our conversation here because the next generation of adjuvant studies in melanoma are now going to think about all of melanoma in the adjuvant setting as really one entity, starting from stage 2B going all the way through stage 4 resected. And that'll be relevant actually as we talk about the next abstract that will come in this discussion. Dr. Diwakar Davar: Just to underscore, positive RFS data, positive DMFS data, and now this therapy has currently got regulatory approval in this investigation and is approved in the United States and certainly in Europe and Australia. One interesting point that we will probably have to contend with, and some of the listeners may be thinking about, is overall survival. So the last adjuvant study that demonstrated overall survival benefit was actually ipilimumab, and increasingly, the Illuminati in melanoma do not believe that we will ever see OS benefit in this disease going forward, even though it has to be an endpoint in all registration phase 3 trials. So, Jason, what are your thoughts about whether or not we'll have a positive OS readout, and even if we don't, why this is still a very important advance in this disease at this time? Dr. Jason Luke: Your points are well taken. I think it's unclear, probably trending towards unlikely, that we would see an overall survival advantage in this trial given that we have not seen that in the stage 3 adjuvant studies. Now people can debate if, whether or not overall survival is the only meaningful endpoint for patients. I personally do not believe that's true. And to me, preventing recurrence has a value in and of itself, whether or not that's connected to overall survival. And part of the reason that I say that is that for an average patient, the median patient on a trial, of course, we can tell them treatment now, treatment later. It's a wash when you look at the overall study. And yet at the same time, for an individual person who's facing melanoma or cancer, generally they're not going to be the average patient; they're going to be one patient. And it's very possible they could end up with the type of recurrence that in fact is not highly treatable at that time. So I think that's really the nuance that goes into those adjuvant discussions. The regulatory endpoints have been recurrence in melanoma for a long time. And I think it's important that patients understand the pros and the cons of each. The complexity in adjuvant therapy and neoadjuvant therapy is you don't necessarily know that you had to have it. You're only really going to know whether or not it didn't work if you recur later on. But to me and in my clinic, most patients are willing and interested to want to pursue those therapies in the perioperative setting to try to reduce the possibility of ever developing metastatic disease. Dr. Diwakar Davar: Excellent. So I think key advance [is] positive DMFS data to add to the earlier reported RFS data and truly practice-changing. So, moving on to the next study, LBA9503. This is the phase 2 trial of the Moderna vaccine. This is the trial that almost every medical oncologist knows intimately or has been called about by either the press or patients. So what is this study? This essentially is a phase 2 trial evaluating the personalized cancer vaccine PCV Moderna, made by Moderna, the mRNA vaccine, that is being studied in combination with anti-PD-1 pembrolizumab in the stage 3 BCD and stage 4 resected setting. And so there are really two very interesting results here because this is an update of the RFS data that was presented at AACR earlier this year, which was positive. What are your takes on the DMFS results, and maybe a quick blurb on how is this vaccine generated for those who may not be aware of this particular platform? Dr. Jason Luke: Yeah, certainly. So this individualized neo-antigen therapy, as we're now calling it, is a technology platform that allows us to develop an individualized treatment for each patient based on their own cancer. So taking the actual tumor specimen, whole exome sequencing is performed to try to identify changes in the DNA, and then through a reasonably complex bioinformatic pipeline, those mutations that are likely to generate proteins that can be bound within class 1 MHC molecules are then identified in the computer and then synthesized with an mRNA, very similar to the way that the COVID vaccines were made. And then that becomes the actual drug. So in the clinical trial, which was KEYNOTE-942, about 160 patients were randomized 2 to 1 to receive either pembrolizumab for a year as per standard adjuvant therapy but then with the addition of the individualized neoantigen therapy starting with dose 3 and throughout the rest of the year versus the control arm of pembrolizumab as the standard of care. As you mentioned, the recurrence-free survival were highly positive in this trial when it was first presented earlier this year, and at the updated ASCO we see the 18-month RFS in which the hazard ratio continues to be maintained. But I think most impressively is that distant metastasis-free survival, where we saw an even greater advantage for distant metastasis-free survival – hazard ratio here being 0.35. And so that's a huge advantage for distant metastasis-free survival in this population of patients. And very interestingly in the clinical trial, when you follow the Kaplan-Meier plots, what you see over time is that they overlap almost the entire first year. And it's really at about a year, basically after the vaccine has had time to kick in and these neoantigens have been identified, that we then start to see the separation of the curve, which looks very flat over time. And so I think this is a very, very exciting kind of technology platform and very exciting results because there was minimal increase in toxicity – just at the site of the local injection – for the addition of the individualized neoantigen therapy. And beyond that, hypothetically, this is not necessarily just a melanoma thing. So, of course, based on these phase 2 results, a phase 3 clinical trial called KEYNOTE-V940 is going to be launching later this year to compare pembrolizumab versus pembrolizumab plus this V940 individualized neoantigen therapy. And we're very, very excited in the field to see what those results will look like because the concept here is you could really, really enhance adjuvant therapy with this kind of an approach. Meanwhile, we're just about to talk in a little bit about all the exciting things happening in the neoadjuvant space as well. And with no increase in toxicity, obviously, that looks really good. Suffice it to say that this technology is not specific to melanoma but rather could be applied almost to any cancer where we think about an adjuvant therapy platform. So I think the results are very, very exciting. It is a phase 2 study and it does have some caveats about not being the largest study and some other things, but you can't help but be impressed by the data that have been presented here so far. Dr. Diwakar Davar: One important plug, I guess, in addition to that is that you mentioned that there's data using the platform in other diseases. And one really exciting paper that came out recently was Dr. Vinod Balachandran's paper; for those who haven't read it, it's in Nature, and really in a very provocative proof of concept study, they studied the platform, the vaccine plus checkpoint inhibitor therapy plus chemotherapy in a highly adverse tumor patient population. So these are patients with resectable pancreatic cancer who had the vaccine generated from pancreatic cancer that was resected after Whipple surgery. And extraordinarily, out of the 16 patients who had immune responses, 8 of them did not have relapse at a median follow-up of almost a year and a half, which is really quite extraordinary given the lack of really any effective drug outside of chemotherapy in that setting. So, the point that you're making regarding the benefit of this therapy, suggesting that it could potentially be extended to not just melanoma, potentially other tumors such as highly immunogenic tumors, and potentially even nonimmunogenic tumors such as pancreatic cancer, really suggests that this is going to be a very exciting landscape. And potentially this area, adjuvant therapy and neoadjuvant therapy, like we'll talk about, is potentially an area in which other drugs and potentially combinations will be developed. So next, we will be discussing 3 abstracts evaluating the theme of combinations, and these abstracts are 9501, 9502, and 4010. Abstract 9501 is an evaluation of the combination of fianlimab and cemiplimab anti-LAG-3 and anti-PD-1, respectively, in advanced melanoma, specifically focusing on the post-PD-1 experience in this disease by Dr. Omid Hamid. 9502 is the updated 2-year survival results from RELATIVITY-047, which evaluated nivolumab and relatlimab against nivolumab alone in frontline metastatic melanoma. And Abstract 4010 are the results from the MORPHEUS platform study, specifically looking at tiragolumab and atezolizumab in patients with advanced unresectable HCC. But focusing on 9501 and 9502, Jason, what do you make of the combination of fianlimab and cemiplimab post-PD-1 setting? Dr. Jason Luke: I think the data look very intriguing for this second combination of PD-1 and LAG-3 combination. When nivolumab and relatlimab, the approved LAG-3 inhibitor, kind of burst on the scene a couple of years ago, it was somewhat to the surprise of a lot of people in the community who had really come to think that while PD-1 and CTLA-4 were core molecules for therapeutics and cancer, that we just weren't ever really going to see something else come along in checkpoint blockade. And so nivo and rela got approved. We'll talk about them again in a second. But the data now coming forward for another PD-1 LAG-3 combination, again with cemiplimab PD-1 and fianlimab LAG-3, looks very, very promising. So in Abstract 9501, they updated a phase 1 expansion cohort, phase 2 cohort looking at patients across the various different settings. And whereas in the treatment naive frontline metastatic setting they had previously described about a 63% response rate, they saw a similar level of response rate in patients who had previously gotten adjuvant anti-PD-1, had a period of time off treatment, and then were treated again. And that was reassuring because it suggested that this is still an active combination even with prior exposure to IO in the past. Now, the thing that I found to be the most interesting about this combination was whereas with nivo and rela, at least from the RELATIVITY-047 phase 3 trial, it looked like there was less benefit in some of the high-risk population cohorts, at least for this combination in early testing for cemi and fian; like we talk about it sometimes, we saw there was a high response rate even in patients with liver metastases and some other high-risk features. And so I think this combination looks quite potent, and I'm very excited to see what the data will look like. I think it's very unlikely we'll ever actually get a randomized trial of two PD-1 LAG-3 combinations against each other. But suffice it to say that the data we've seen so far for fianlimab LAG-3 with cemiplimab PD-1 looks very intriguing. It certainly justifies the frontline metastatic phase 3 and the adjuvant phase 3 trials that are already in planning or ongoing. Dr. Diwakar Davar: So one thing to consider is on the RELATIVITY-020 trial – the early trial that was led by Dr. Ascierto that really took a long time to read out – the response rate in patients with prior checkpoint inhibitor therapy was quite low. In fact, the data was quite surprising, as you'd mentioned that we had even seen this movement in the frontline setting because the response rate by BICR was only about 12%. So do you feel like the 2 LAG-3 inhibitors are fundamentally different? And if so, can you speculate as to why that might be? Again, with the caveat to the fact that these are very early data and we don't have enough information. And maybe we can also talk a little bit about the 2 pending trials that are ongoing in the advanced and adjuvant therapy landscapes perspective. Dr. Jason Luke: I think we don't have enough data yet to truly understand whether or not they're really different. The trials that have been run so far are so different that it's hard to compare things back and forth. You can notice that the dose, the milligram dosage of fianlimab in terms of anti-LAG-3 is quite a bit higher, like a log fold higher almost than with relatlimab. And so there's some question of whether or not just merely more drug-blocking LAG-3 might in fact be more efficacious relative to the dose that's approved for relatlimab in melanoma. But beyond that, I think the data hold up very well for this new combination, again noting all the caveats about cross-trial comparison to, say, it looks to be at least as potent, possibly more potent than the relatlimab combination. But again, I think probably we need to see the data from randomized trials and how that fits into the landscape when the trials actually read out because there's a lot of things going on in melanoma that are likely to change between now and then. Dr. Diwakar Davar: So just to draw people's attention, there are actually 2 ongoing pivotal phase 3 trials: fian plus cemi versus pembro in patients with advanced metastatic and locally advanced, previously untreated melanoma, as well as an adjuvant trial of the combination against pembrolizumab. Again, highly high-risk resected melanoma. These trials are ongoing. We don't have the results yet and we are looking forward to them. Now, 9502, a 2-year RELATIVITY-047 result presented by Dr. Hussein Tawbi. Dr. Jason Luke: So this is the study we were just alluding to before, the randomized phase 3 study of nivolumab versus nivolumab plus for relatlimab. To me, the most useful data sort of updating with this two-year survival follow-up is to show the maintenance of benefit between the 2 arms. And so, consistent with what we saw with nivolumab and ipilimumab, there seems to be a persistent delta between the arms for both progression-free and for overall survival out over that extended period of time, where we can see with that updated data now, at 2 years, that it's 52% of patients still alive on the relatlimab combo versus 42 with nivolumab. And it does seem like this is probably a higher-risk population of patients than participated in CheckMate-067. So it's a little bit difficult to compare the landmarks except to notice that that difference between the control and experimental groups is consistent over a long period of time and that there were no new safety signals either, and so that was also reassuring. To me, the most interesting nugget of data in the abstract, though, is to look at what happened to patients after they were on the first-line treatment. So one of the big questions in our field is really “If patients get nivolumab and relatlimab upfront, what should they get after that?” Should they then get nivo plus ipi, or vice versa? And I think we don't have an answer clearly to that question just yet. There was an important letter to the editor of the New England Journal now going on about a year ago by Alex Menzies and colleagues that suggested that the use of ipilimumab was attenuated, the utility of it, after a prior exposure to nivolumab plus relatlimab. They quoted a response rate on the order of only about 10% for patients who got an ipilimumab-containing regimen after initial LAG-3. In the data from Hussein Tawbi at ASCO, however, in a small number of patients, caveat, the response rate was more in sort of the low 20% range, 22% to 25%. And so that would be a much more meaningful and important sort of consideration. If we do have independent activity, then lining up sequential therapies and the toxicities associated with each will become increasingly important as we think about how to maximize these kinds of treatments for our patients, but important longer-term data to show that the benefit is holding up and it's safe, and some new insights into what to do after progression on one of these regimens. Dr. Diwakar Davar: So, pivoting slightly to combinations, we are going to be discussing a combination of TIGIT plus checkpoints. So tiragolumab is the FC-active TIGIT inhibitor from Regeneron-Roche and this is currently in multiple pivotal phase 3 trials, several of which have been negative, including SKYSCRAPER-01 in non-small cell lung cancer and SKYSCRAPER-03 in small cell lung cancer. The MORPHEUS platform trial essentially is a platform study evaluating multiple different combinations, in this case in liver cancer. And so we have a very interesting Abstract 4010, which is giving us an early readout of the evaluation of tiragolumab plus atezolizumab along with bevacizumab in unresectable, locally advanced or metastatic hepatocellular carcinoma giving us a result that is a little different from what we had seen from the prior negative results of TIGIT. So Jason, what do you make of these early results in the advanced HCC setting? Dr. Jason Luke: I think these are cautiously intriguing results to really highlight the point is the third checkpoint possibly being LAG-3, now a fourth checkpoint maybe with TIGIT, but with all the caveats that you talked about. In this study, the flow is that there's a continuously accruing control arm which in hepatocellular carcinoma is a combination of atezolizumab plus bevacizumab, and then other arms are added where you add in a third agent. In this case, it's the anti-TIGIT tiragolumab. And in an intriguing fashion, the response rate to the triplet was 42.5% compared to the doublet which was only 11%. So that's a pretty big difference in this population. Now, it wasn't the largest study, only 58 patients, but it was a randomized clinical trial. And so I think those data really make people kind of open their eyes again. It's worth a little bit of a caveat here that HCC is an unusual cancer in that what is deemed to be unresectable and therefore amendable to systemic therapy is a moving target and that requires multidisciplinary evaluation of patients. And so I think a larger number of patients would really be needed to fully understand this. But certainly, a fourfold increase in the benefit or in terms of response rate looks quite intriguing. I think the other piece of this is to be just cautious a little bit was when the initial data in non-small cell lung cancer in the CITYSCAPE study came forward, and they looked roughly sort of like this: There was more than a doubling in the PFS and the response rate, which is what triggered all of those phase 3 studies. So to me, this is enough to continue to be very interested in TIGIT as a therapeutic target. And there are many phase 3 trials already ongoing. And so I think, I'm cautiously optimistic that some of those actually will be positive and we could see more movement around TIGIT becoming a standard of care agent. Dr. Diwakar Davar: To your point about TIGIT being an interesting target, recent data looking at the neoadjuvant landscape in melanoma from Merck, with Merck, also FC-active TIGIT and also some data from authors looking at that TIGIT also presented in this case at ASCO specifically from the ARC-7 study. So very interesting target. Several pivotal trials have been announced. Do you know of any trials that are ongoing in the adjuvant setting in other diseases? Dr. Jason Luke: Well, as you alluded to, the vibostolimab data in melanoma for TIGIT in the neoadjuvant setting was interesting. And in fact, that has been enough to trigger a global, randomized phase 3 adjuvant study of pembrolizumab and vibostolimab versus pembrolizumab in melanoma. And that sort of takes us back to the beginning of our discussion here, building on the KEYNOTE-716 data. So, yes, TIGIT will be moving forward in the adjuvant space in melanoma and obviously at a static setting for several different tumor types with a PD-1 or PD-L1 backbone. Dr. Diwakar Davar: So now pivoting towards neoadjuvant therapy and non-small cell lung cancer. The standard of care in this setting was established by the CheckMate-816 trial that essentially established nivolumab plus chemotherapy in the setting of resectable non-small cell lung carcinoma path. Response rate in this setting is approximately 21%. And we have several studies that are essentially looking at novel combinations or in this case, different PD-1 inhibitors in this setting. So Abstract 8500 essentially looked at nivolumab plus relatlimab from a NEOpredict-Lung trial. Jason, do you want to tell us a little bit about this? Dr. Jason Luke: Yes, I think this is a very interesting study and that this is sort of our first peek at targeting LAG-3 in the context of lung cancer. So obviously we talked about LAG-3 for melanoma. Although the audience is probably aware that there have been neoadjuvant data for LAG-3 with relatlimab in melanoma that substantiated the phase 3 data for the metastatic setting. So one of the questions as we start to apply the LAG-3 in other diseases would be, “Do we see it hold up in both metastatic disease and in the neoadjuvant space?” But in this study, while there were no changes in the safety profile; it didn't impact on whether or not patients could have surgery. There really didn't look to be a big difference in this study between nivolumab and nivolumab plus relatlimab, with the major pathologic response as you alluded to right around 30% for both arms. Now, it wasn't really the biggest study, but that's certainly quite a bit in contrast with what we've seen in melanoma, where with a PD-1 inhibitor you get again 25%-30%, but with adding on LAG-3, that pushes you up closer to 60%. So I think these were very interesting data that probably put a little bit of an eyebrow raise to say, “Well, let's see what happens in the metastatic setting in lung cancer with the addition of relatlimab LAG-3 on top of a PD-1.” I think it might not be quite so straightforward as what we saw in melanoma, but we'll look forward to those results because those phase 3 trials in metastatic lung cancer should be maturing sometime in the next year or two. Dr. Diwakar Davar: The theme of neoadjuvant therapy non-small lung cancer, LBA100, which has again previously been discussed in an episode of this podcast by Dr. Jack West and Dr. Velcheti is KEYNOTE-671. And this is a study essentially that looked at pembrolizumab or placebo with platinum-based chemotherapy doublet and followed by resection. So again, a direct parallel to CheckMate-816. What do you make of the results that were reported by our colleagues in this setting, Jason? Dr. Jason Luke: So not to rehash this, because our colleagues in the lung cancer group have already discussed this at length and obviously they're experts in that disease, but we'll just note that there was a threefold increase in major pathologic response, which turned into a major advantage for event-free survival. And so I think this is at least the third PD-1, PD-L1 combination regimen for neoadjuvant lung cancer that looks very, very promising. It certainly, to me, seems like neoadjuvant consideration really should be the standard of care already moving forward. To me, what the big question that is left with is “Do we still need the adjuvant component after we give the neoadjuvant?” So, some of the trials are including neoadjuvant and adjuvant, some of them are only neoadjuvant. And I think that's going to be a really important question as we move into the future, both in terms of what is that contribution of the adjuvant component, and then again, going back to earlier in our discussion here, if there could be a major advantage to adding individualized neoantigen therapy, maybe it is important to have both. But I think that's one of the big questions we have to get teased out by the field over the next couple of years. Dr. Diwakar Davar: And finally pivoting towards cutaneous squamous cell carcinoma. We have 2 abstracts discussing perioperative therapy. So cutaneous squamous cell carcinoma is a high-TMB tumor. The median tumor mutation burden in this disease is threefold that of melanoma. This is a disease in which checkpoint inhibitor therapy is approved as a single agent both with pembrolizumab and cemiplimab on the basis of nonrandomized phase 2 trials. And increasingly, there has been early development in the perioperative setting. The first data in this space came from our colleague Dr. Gross at MD Anderson, who reported in a small, nonrandomized phase 2 trial of 20 patients, a path CR rate with two cycles of cemiplimab at approximately 50%. A larger multi-institutional phase 2 trial demonstrated that a longer duration of perioperative therapy of four cycles or 3 months of cemiplimab did not particularly improve the path response rates. The response rates were similar at approximately 50% as well. And what we have right now are 2 other trials. The first is the MATISSE trial, Abstract 9507 ,that evaluated nivolumab or nivolumab plus epilimumab in this disease. And the other one was the NEO-CESQ trial, or Abstract 9576, that evaluated neoadjuvant plus adjuvant therapy that's cemiplimab in the high-risk patient population. So we're starting with 9507. Jason, what do you make of the ipi and ipi-nivo data reported in this setting? Dr. Jason Luke: So I think this is a really interesting study because I think part of the intent is the clinical aspect of how you manage patients with cutaneous squamous cell carcinoma. For those that don't do cutaneous oncology, many of these patients have the development of lesions, which can be actually quite difficult to resect in a way that's not otherwise mutilating or cosmetically quite problematic. And that was part of the impetus for this trial where, again, they looked at either monotherapy PD-1 or a PD-1 plus CTLA-4, and they saw great success. As was predicted based on the other data that you alluded to, response rates are more than 50% near 60%, with actually a substantial number of patients on the trial actually refusing to have surgery after they received their neoadjuvant therapy because they were so certain that they had had a good outcome. So I think these data are quite reassuring in the context of all of this emerging data around cutaneous squamous cell carcinoma. We'll talk about this NEO-CESQ trial in just a second, but I think it really is emerging to be the standard of care very soon for the use of perioperative PD-1 for cutaneous squamous cell. Dr. Diwakar Davar: What do you feel about the dose and schedule of checkpoint inhibitor therapy used here? So the dose of ipilimumab used was ipi-1 and not ipi-3, and they waited 4 weeks. So when patients only got two cycles of Q2 weekly nivo, and one cycle of ipilimumab, do you think the responses would have been deeper if they'd waited longer? Dr. Jason Luke: I think it is possible that they might have been deeper, although I'm not totally sure about that. One of the other abstracts we're not directly mentioning here was a study in Merkel cell carcinoma which suggested that in fact, adding ipi and that also highly immuno-oncology-responsive tumor type did not add to the response rate. So I'm not totally sure about that. I think rather what would be most interesting here is sort of the sort of next generation of biomarker work. As part of their presentation, the MATISSE trial team showed gene expression profiling that really strongly identified which patients were going to do well on the trial. And I think that's probably eventually going to be how we need to think about this. There are patients in the neoadjuvant setting who are going to do really well with anti-PD-1 alone. And then for those who aren't, that's where we probably really need to think about do we need combos, how long to give the treatment, etc. And I think we're really only on the cusp in the beginning of this, which is exciting as we think about moving into the future. Dr. Diwakar Davar: Certainly, many combinations are being evaluated in this space and we are very excited for the data that it's about to hopefully come in the next couple of months to years. So the NEO-CESQ – it's quite a puzzle as to how to pronounce this acronym – and this evaluated cemiplimab in the high-risk setting. So it's worthwhile noting that Dr. Gross's first trial looked at high-risk stage 2, 3, and 4 disease. So the context of cutaneous squamous cell carcinoma that's node-positive disease and distant metastatic disease that is in one location or patients with node-positive disease invention. And his multi-institutional cemiplimab trial of four cycles evaluated included patients with stage 2, 3, and 4 disease. So here in a study just in stage 3 and 4 diseases, Dr. Ascierto reported the results of 2 cycles of cemiplimab and importantly, these patients had both the neoadjuvant and the adjuvant portion of cemiplimab. So, Jason, you mentioned earlier that one of the key aspects that we start thinking about neoadjuvant therapy is exactly how much do you need. Do you need both the pre-surgical therapy and the post-surgical therapy? Is the presurgical therapy enough? After all, neoadjuvant response equals cure. How much benefit are you getting from post-surgical portions? So what do you make of the results that they've seen here and what is the impact? How do you think we'll be disentangling the impact of the neoadjuvant and the adjuvant portion of the immunotherapy upon response and survival? Dr. Jason Luke: So just to leverage those comments, I think these data are reassuring because in this higher-risk group of patients, they saw excellent outcomes very similar to what Gross et al had previously reported. So that's good. To your question about how we are going to disentangle this adjuvant versus non-adjuvant question, there's a trial in melanoma called the NADINA trial which is ongoing now in which the use of the adjuvant therapy is actually risk-adapted. So after patients have an initial neoadjuvant treatment they're evaluated, and if they have had a pathologic complete response, they're actually going to stop that treatment and they're not going to give the neoadjuvant therapy. And so I think obviously it's a slightly different disease, but those kinds of data, I think, will be very meaningful to help us sort this out. And I'm not sure whether or not in cutaneous squamous we would need a different trial than in melanoma, although I think in a different tumor, maybe like, say, lung cancer, you probably would need a dedicated study to try to look at that because I think just the responsiveness to checkpoint blockade is going to vary quite a bit once you get outside of cutaneous oncology. But to summarize, reassuring that a similar pathologic response rate, and I think this question of adjuvant or nonadjuvant, I think that's the next question we've got to answer in the field. Dr. Diwakar Davar: We have now come to the end of our back-and-forth discussion on these very, very exciting abstracts. So Jason, thank you for highlighting these advances and for engaging in a robust discussion. Dr. Jason Luke: Thanks for having me. Dr. Diwakar Davar: And thank you to our listeners today for taking the time to listen to this podcast. You will find the links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear in the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcast. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:  Dr. Diwakar Davar  @diwakardavar  Dr. Jason Luke  @jasonlukemd    Follow ASCO on social media:   @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures:     Dr. Diwakar Davar:    Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences   Consulting or Advisory Role: Instil Bio, Vedanta Biosciences   Consulting or Advisory Role (Immediate family member): Shionogi   Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences   Research Funding (Inst.): Zucero Therapeutics   Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy   Dr. Jason Luke:     Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical , Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX   Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine   Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure   Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)   Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio 

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ASCO23: RELATIVITY-047, CheckMate-038, and Other Advances in Immunotherapy

Play Episode Listen Later May 25, 2023 28:57

Dr. Diwakar Davar and Dr. Jason Luke discuss advances in melanoma, including targeted therapy and the addition of LAG-3 inhibitors to checkpoint therapy, as well as promising checkpoint inhibitors in cutaneous squamous cell carcinoma and Merkel cell carcinoma in advance of the 2023 ASCO Annual Meeting. TRANSCRIPT Dr. Diwakar Davar: Hello, and welcome to the ASCO Daily News Podcast. I'm your guest host, Dr. Diwakar Davar, and I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. I'm delighted to welcome my colleague and friend, Dr. Jason Luke. Dr. Luke is an associate professor of medicine and the director of the Cancer Immunotherapeutic Center at the University of Pittsburgh's Hillman Cancer Center. He is a very, very well-renowned physician-scientist who has done fundamental work in developmental therapeutics and also in melanoma. Today, we'll be discussing some key oral abstracts highlighting advances in immunotherapy in the cutaneous malignancy space that will be featured at the 2023 ASCO Annual Meeting. You will find our full disclosures in the transcript of this episode and the disclosures of all guests on the ASCO Daily News Podcast are available in our transcripts at asco.org/DNpod. Jason, thank you for coming on the podcast today. Dr. Jason Luke: Well, thanks so much for the opportunity. Dr. Diwakar Davar: So, we will go right ahead into the abstracts and the first one we thought we'd discuss is Abstract 9502, which is the RELATIVITY-047 study, specifically the 2-year results. This is the update. This has also been concurrently published at the New England Journal of Medicine Evidence online. And so in this publication and oral presentation, Hussein Tawbi, Georgina Long, and colleagues are talking about the nivo-rela data in the context of metastatic melanoma. So what is your take on this? What is your take on the data both presented and published and how would you contextualize this for the audience? Dr. Jason Luke: Right, so the RELATIVITY-047 study, as people will remember, randomized treatment-naive patients with metastatic melanoma to either receive nivolumab as standard treatment as a monotherapy or the combination of nivolumab and the anti-LAG-3 antibody relatlimab. And that study reported out a couple of years ago showing the improvement in progression-free survival as the primary endpoint. And at the time we saw that difference was approximately a 6-month absolute difference. And eventually, we saw there was an increase in the overall response rate also, again, approximately on the order of about a 10% change. What was interesting was that the overall survival initially was immature and that was an interesting follow-up point that we wanted to see. So I think what's important in seeing now this 2-year update of these data are the maintenance of the benefit for nivolumab plus relatlimab as compared to nivolumab alone across those measurements of progression-free survival and overall response rate. Interestingly, the overall survival in the clinical trial actually did not meet the pre-specified threshold for statistical significance. That being said, when you look at the data presented in the Kaplan-Meier plots and you think about the difference, it really does appear that there's a clinically meaningful difference between these 2 groups. And the statistical cut point only missed by about .01. And so this is one of those areas where one wonders whether or not subsequent therapies may have impacted on the overall survival calculation because obviously, patients in this trial had not received ipilimumab or a PD-1 CTLA-4 combination. So the take-home message from me in this data set was that the benefit of nivolumab and relatlimab was sustained over time and there was no suggestion of any late toxicities that might make us concerned. One advantage of this combination of nivolumab and relatlimab is the dramatically improved side effect profile relative to nivolumab and ipilimumab. So whereas immune-related adverse events that were serious, grade 3-4 is approximately 50% for nivolumab and ipilimumab, in the RELATIVITY-047 study, we see that the incidence of grade 3-4 toxicities for nivolumab and relatlimab is 17.2%, so that's less than half. So that's pretty attractive. And when we think about frontline management of patients, I think these data really support that nivolumab plus relatlimab is a reasonable consideration for some patients. And now I think the future question is really going to be, okay, well then who should get nivolumab and relatlimab versus who should still get nivolumab plus ipilimumab? Obviously, these data do not address that, and I think that that's probably the most important question for metastatic disease that's probably on the horizon. Dr. Diwakar Davar: Thank you, Jason, those are all fantastic points. It is interesting to note that as a result of the data, or really the lack thereof, the combination is actually not being launched in certain countries. So, for example, the German Health Authority, GBA, the Federal Joint Committee in Germany has decided against the acceptance of this agent because it does not accept event-free survival (EFS) as a patient-relevant endpoint. So it's interesting that we have an agent that is now going to be FDA-approved. It's already FDA-approved and available in the United States, but it will not be at least available in Germany and there may be other countries that decide favorably or unfavorably depending on how this OS data is viewed. So pivoting to another LAG-3 inhibitor in this case fianlimab, we're going to discuss Abstract 9501. So Abstract 9501 essentially is describing a phase II trial that evaluated the LAG-3 inhibitor, fianlimab, along with the anti-PD-1 inhibitor, cemiplimab from Regeneron. The data is slightly different from what we have seen with RELATIVITY-047, the Opdualag combination. So Jason, how would you contextualize the fian-cemi combination in advanced melanoma in the context of what we've seen with RELATIVITY-047? If you could help us with that, please. Dr. Jason Luke: Yeah, absolutely. So before we dive into this specific abstract, it's, like you mentioned, probably useful to just put all of this in context. Targeting LAG-3 as an immunomodulatory approach has actually been in clinic for a decade approximately. And so the relatlimab phase 1 started quite a long time ago. And there was data for nivolumab and relatlimab in PD-1 refractory patients with melanoma that showed not a tremendously obvious level of activity. And so it was thought there that the only place they would see that activity was to go to a frontline randomized phase 2 and then phase 3 trial, as we just discussed. In contrast to that, given all the data that had come forward about LAG-3 targeting with relatlimab, the group developing fianlimab took a different approach and rather treated a cohort of patients with treatment-naive melanoma to try to get an initial assessment right away of the activity as read out by overall response rate for this PD-1 plus LAG-3 combination, which is cemiplamab plus fianlimab. And these authors have previously presented data about this combination from cohorts of patients who are treatment-naive who received this combination and described approximately a 64% overall response rate. And that's an impressive number in the treatment-naive setting. There's sort of a tension there to sort of say, well, wait a minute, the response rate in this single-arm study is 64%, but in RELATIVITY-047, the response rate was lower for the LAG-3 combination and I think that's not a fair comparison. We have to realize this is a much smaller group of patients that has the potential to have been somewhat biased towards a better cohort just because of where and when they were recruited to participate in this trial. All the same, I think that number does look impressive and suggest that this combination is active in the frontline. Specific to this abstract, though, what the authors presented here was to update those previous data and then specifically also to focus on a cohort of patients who are allowed to have had previous treatment in the perioperative setting. So either neoadjuvant or adjuvant therapies. And in a subgroup of patients, they observed that even in the patients that had received adjuvant anti-PD-1 who went on to then progress later, they got actually a similar overall response rate at approximately 60% even in that group. And so I think that that seems like an exciting number as well. One would on first principles think that if patients got an adjuvant anti-PD-1, then a PD-1 LAG-3 combo could be less active. When and how the patients progressed or did not on that adjuvant therapy, however, I think makes a big difference. And given the relatively small sample size of patients that were included in this report, which is on the order of 20-ish patients who were in the previous PD-1 treated adjuvant cohort, I don't know that we can make super broad analyses trying to compare across the development programs. What I would take from this abstract, however, is that it does appear that this other PD-1 LAG-3 combination cemiplamab plus fianlimab is also very active and certainly deserves to be investigated in similar clinical trial contexts as the nivolumab plus relatlimab combination that we previously discussed. And while it's not specifically stated here, that is happening, there is a frontline phase 3 trial for this combination of fianlimab and cemiplamab as well as adjuvant considerations, also ongoing. Dr. Diwakar Davar: So, thank you. We've seen a lot of LAG-3 data this last 2 months, the phase 2/3a RELATIVITY-020 trial has just been published in the JCO, I encourage people to read that. And so that was the evaluation of nivolumab and relatlimabin the post-PD-1 patient population that Jason alluded to, where the response rate that was observed was 12%. So we've seen a lot of interesting data, a lot of interesting survival data, and now a new potential combination with LAG-3 with fianlimab and cemiplamab from Regeneron. So it'll be a very interesting next couple of years as we see whether or not this new combination, how it shakes up against the established nivu-rela combination, again, albeit with the limitations of cross-trial comparisons and also how it performs against cemiplamab in this ongoing, as you alluded to, ongoing global phase 3 trial. So, pivoting away from melanoma, now addressing the context of another cutaneous malignancy, a very high-risk one, Merkel cell carcinoma. So, Merkel cell carcinoma for those who are not necessarily treating a lot of this is a very rare and very aggressive cutaneous tumor. It's a neuroendocrine tumor of the skin. It's a cancer that's typically associated more than about 60% of the time with a cancer-causing virus, an oncogenic virus known as a Merkel Cell Polyomavirus. And in this setting, checkpoint inhibitor therapy has been approved for the last couple of years, initially with a PDL-1 inhibitor, avelumab, and then more recently with a PD-1 inhibitor, pembrolizumab. And, at this point in time, there are three FDA-approved agents that are checkpoint inhibitors that are available for the treatment of this disease. And CheckMate-358 was essentially a trial of nivolumab plus/minus ipilimumab in the setting of this Merkel cell carcinoma. So, Jason, what are your thoughts on how the addition of ipi did in this setting [in Abstract 9506]? Dr. Jason Luke: Yeah, so I think this is a really interesting abstract because there's a slightly more context even than what you alluded to there. This study is an open-label, multi-cohort, but single-arm investigation where one cohort of patients received nivolumab alone and the other cohort received ipilimumab. It needs to be buttressed by a previous publication in The Lancet last year by the group at the Moffitt Cancer Center who also did a prospective study looking at nivolumab and ipilimumab. In that previous study that the Moffit group did, they got a response rate of 100%. All patients responded to the combination of nivolumab and ipilimumab in their study and that was quite provocative, suggesting that while anti-PD-1 alone has about a 50% response rate, adding ipi in that scenario then took it to 100. So these data were very much of interest because this could be a confirmatory data set to suggest for this rare tumor that perhaps a combination regimen should be preferred. Of course, one has to remember that adding ipilimumab to anti-PD-1 substantially enhances the toxicity profile. And these patients tend to be elderly that develop this kind of cancer, Merkel cell carcinoma. So that's a rather important caveat. Just to get to the crux of what happened in this trial. As opposed to the previous Moffit trial, there actually did not appear to be a major increase in the benefit of adding ipilimumab, at least in this trial. Because again, in parallel cohorts, the NIVO monotherapy arm had a 60% response rate, which is roughly a little bit higher, but roughly in line with what we've seen previously. And the response rate to nivolumab plus ipilimumab was 58%. So, I mean basically the same. So, how can it be then, that we have this previous very high-profile publication that says 100% response? Now, we have a second publication that says adding ipi doesn't do anything - that's confusing, and I think it'll be really important to try to look at what were the differences between these two cohorts of patients. Did one of them have higher risk features, greater disease burden, et cetera? We don't really know that just yet, but trying to tease that out will be important. This data also emphasized, though, the complexity around the dosing of ipilimumab. And in melanoma, we never really figured out what the best dose of ipilimumab was to give either alone or even in combination with a PD-1. And we don't really have time to get into all of it right away here, but there are multiple studies in melanoma that would suggest that giving ipi on an every 3-week dosing schedule is superior to giving it on a 6-week dosing schedule. In this study, they did use the 6-week dosing schedule. So, whether or not that could have made a difference, I guess, is unknown. But I would notice that in the previous Moffitt trial, they also used that six-week dosing schedule. This one's a head-scratcher for why did these data not confirm a previous data set? But for the time being, I think this emphasizes that PD-1 monotherapy really is the standard approach that should be considered for patients with metastatic Merkel cell carcinoma. Dr. Diwakar Davar: That's great, Jason. And so, again, it's a very tough patient population. These are very rare patients. The Moffitt trial that Jason alluded to essentially was a trial that had in each arm, there were approximately 25 patients, of which 13, or between 11 to 13 patients were actually checkpoint inhibitor naive, wherein the dramatic 100% response rate was seen. And this is a trial where at least in this update, we've got about 25 patients in nivo monotherapy, I mean in 43 patients. And so, in a disease that is thought to be extraordinarily sensitive to checkpoint inhibitor immunotherapy because of the role of the virus and the high TMB that it's associated with, it is very interesting that the addition of an additional checkpoint inhibitor did not appear to improve outcomes. But as you alluded to multiple reasons, but we don't know how it's going to shake out. Next, Abstract 9507 and this is a very interesting trial known as the MATISSE trial. So, in the context of cutaneous squamous cell carcinoma, cutaneous squamous cell carcinoma is a relatively not uncommon cancer, primarily seen in older cancer patients, particularly a little bit more common in men. And in this setting, we've got checkpoint inhibitor therapy that is FDA-approved, at least two of which are FDA-approved right now, pembrolizumab and cemiplamab both were approved in the advanced cancer setting. And we do know that because of the extraordinarily high tumor mutation burden associated with cutaneous squamous cell carcinoma, checkpoint inhibitor therapy has got a very dramatic effect. Response rates are between 35% to 42% with pembrolizumab and 40% to 50% with cemiplamab, depending on whether or not one looks at the relapsed metastatic or the locally advanced patient populations. And interestingly, much like we've seen with melanoma, we have migrated the use of this therapy early in the lines of patients, particularly in the setting of perioperative therapy. So, Jason, how would you contextualize the results of the MATISSE trial in relation to the existing and known data from several of our colleagues regarding the role of what checkpoint inhibitor therapy is doing in terms of organ preservation? Dr. Jason Luke: Yeah, and I think this is an area of tremendous excitement. And as you were alluding to, the activity of anti-PD-1 really was transformative in this disease, which really can be a disfiguring and locally destructive disease. And with that activity for unresectable disease, last year, near the end of the year, there was a first report of a large neo-adjuvant clinical trial in cutaneous squamous which showed really outstanding results in terms of improving surgery and pathologic complete response using anti-PD-1 in that setting. And for this trial, this was a trial done in Europe; they took a similar tact of trying to think about giving anti-PD-1 or anti-PD-1 with anti-CTLA-4 with ipilimumab in that neoadjuvant period to see whether or not they could reduce the use of extensive surgery and/or radiation therapy. The short version is they were able to do that. And so they described 40% of patients with single-agent anti-PD-1 and 53% of patients who received a combination having major pathologic response to treatment. And this was so much so that 10 of the patients who had pathologic responses actually withdrew their consent to go on to have surgery because they decided that they had had such a good effect of the immunotherapy, they weren't willing to put themselves through what was going to be a very difficult surgery. And I think that speaks to the upside potential of these checkpoint immunotherapy approaches in certain settings, specifically here in cutaneous squamous cell carcinoma. Moreover, they describe clinical response in neoadjuvant setting as 50% for PD-1 monotherapy and 61% for the combination and I really think that this is really ready for prime time. With the study published in the New England Journal last year and these data now, I really think the field needs to start moving towards the use of perioperative anti-PD-1 with or without ipilimumab as a standard approach. And I think it's the case that even the NCCN and ASCO and various guideline societies are going to start acknowledging that this ought to be considered for most patients who are facing difficult surgical operations for continuous squamous cell carcinoma. Dr. Diwakar Davar: So, Jason, you bring up a fascinating point, which is the appearance of this in guidelines. So this is undoubtedly extraordinarily good data. It's confirmatory, the pathologic response rates in many ways paradoxically low. You'd expect something about 50% or so. But the reason it's low is because 10% of patients who actually benefited didn't undergo surgery. So really the degree of benefit is tremendous. It's about 50% to 60%. So the fascinating thing in the setting that we'd have is if one is going to try to get the drug FDA-approved, what we now have is the conventional setting in which one needs a definitive endpoint. And at least we know that pathological response rate is not a definitive endpoint in the context of melanoma or, for that matter, cutaneous squamous cell carcinoma. The only setting in which it is a regulatory endpoint is a non-small cell lung cancer or triple-negative breast cancer. But recently there's been some very exciting data from another PD-1 inhibitor called dostarlimab in a trial done by your former colleague Dr. Luis Diaz when he demonstrated a dramatic result of dostarlimab in the context of perioperative rectal cancer where it is micro-satellite high wherein the standard of care is typically very disfiguring abdominal perineal resection. So in the context of some of our listeners who might be thinking a little bit about how this pertains to regulatory approval, what are your thoughts about the paradigm of avoiding highly disfiguring surgery relating to what was seen in the rectal cancer discussion to what we're now seeing with perioperative therapy in the context of cutaneous squamous cell carcinoma? Dr. Jason Luke: I think it's a very important question. And the easy out for diseases that have a pattern of progression that is metastasis is to use event-free survival which can include both the pre-surgical and the post-surgical period in terms of looking for whether or not the cancer comes back. And that works for diseases potentially like lung cancer, like you said, maybe melanoma. In cutaneous squamous cell carcinoma, however, that's not probably going to work because this tends to be a locally invasive and less of a metastatic disease. So here then, we really need to have sort of organization across patient advocacy, dermatology, medical oncology to come up with what the most appropriate considerations are going to be for evaluating that long-term benefit because I think we need a tangible result that we can show the FDA. Everyone is really impressed by these results, and I think that next step is to craft this into a way that we have a measurable output that we can then go to them with and say bless this so that all of our patients can get this kind of treatment. Dr. Diwakar Davar: Really great discussion, Jason. And I think this is going to be an area of particular interest going forward, given both the number of trials that have been conducted in this space and also the role of the very interesting regulatory paradigm that has now been set initially at least with the rectal cancer that is microsatellite high and now potentially we will see with cutaneous squamous cell carcinoma. And so the final abstract that we have selected for you is Abstract 9511. And this is a trial that was conducted by a mutual colleague, Dr. Ryan Sullivan, and his colleagues. And it's essentially a trial of looking at targeted therapy with or without navitoclax in BRAF mutant melanoma patients. And part of the reason to highlight this, it's very interesting preclinical data supporting the addition of navitoclax, b but also a great example of an early trial that came through the CTEP portfolio. And so Jason, can you tell us about why this is exciting and how we might contextualize the addition of navitoclax to the targeted therapy backbone? Dr. Jason Luke: Sure. So listeners will be quite aware of targeting mutant BRAF as a therapeutic strategy across oncology that was really initially pioneered in melanoma with the development of vemurafenib as the first selective BRAF inhibitor. But the field, of course, moved eventually to BRAF and MEK combinations across essentially all settings. We know that dabrafenib and trametinib are now approved pan-cancer for anywhere we find a BRAF V600e mutation. In the context of melanoma, looking at mechanisms of resistance, we observed that they were quite heterogeneous with reactivation of elements of the mitogen-activated protein kinase pathway, the MAPK pathway. But also there were metabolic changes in the cancer cells themselves which could drive resistance and were downstream of some of those reactivation signaling points. So one of those is the induction of anti-apoptotic machinery in the cell. So activation of BCL-2 or Bcl-xL to try to save those melanoma cells when they were under stress by blockade with BRAF and MEK inhibitors. And that observation was made now about a decade ago or more. And that raised the possibility that repurposing a drug that was being used actually in the chemo malignancy space might be useful in augmenting targeted therapy. And that's where we come in with the navitoclax as a BH3-mimetic that can actually knock down those antiapoptotic proteins, BCL-2 Bcl-xL. And so that was the context for this initially phase I clinical trial of combining navitoclax with the dabrafenib and trametinib. And those data supported the safety of doing that and moved to this study, which was a randomized phase 2 study of that triplet regiment versus the dabrafenib and trametinib alone. And so this study started quite a long time ago, before the sort of initiation or widespread use of anti-PD-1 antibodies. And so it had to kind of undergo some various iterations throughout its course but eventually has now read out. And it had two primary endpoints, with one being focused on improving the complete response rate for targeted therapy because that's been associated with long-term outcomes as well as to look at the maximum tumor shrinkage of patients within this trial and of course to look at other endpoints like response rate, progression-free survival, et cetera. About half the patients who participated in the trial had prior immune checkpoint blockade and they were actually distributed evenly across the two arms. So we think that probably won't impact on the outcomes. And what was observed in the clinical trial was that in fact, the triplet did improve the complete response rate for targeted therapy. So navitoclax plus dabrafenib and trametinib had a complete response rate of 20% versus dabrafenib and trametinib alone being at 15%. Both of them had an overall response rate in the 80% range, with slightly higher for the triplet at 84% versus 80% for the double-edged standard therapy. There was also a suggestion that there may be a disproportionate benefit for the triplet actually in patients with smaller baseline tumors. And we know that the efficacy of targeted therapy is more pronounced in the lower-volume disease state. And so overall, when we look at this without really adding much toxicity, I think this is an intriguing place to look at further drug development. BRAF and MEK inhibition has been a backbone therapy in Melanoma for a long time, but we really haven't been able to move past it or augment it in any real way because of the heterogeneity of treatment resistance. And here, by going after metabolic changes, we perhaps might have the opportunity to enhance our targeted therapy somewhat further. And so we'll look forward to further results investigating this regimen in subsequent clinical trials. Dr. Diwakar Davar: Fantastic discussion, Jason. So these are all great insights. As you've heard, we've now discussed a couple of key abstracts covering major topics that will be presented, major themes of the malignancy space at ASCO 2023, including the addition of a lactate inhibitor to checkpoint in both a randomized large phase 3 trial and a smaller phase 2 trial, the context of targeted-therapy in melanoma making another forerun in the post-3c setting. And two very interesting studies I have looked at, checkpoint inhibitor therapy in the context of cutaneous squamous cell carcinoma and Merkel cell carcinoma, addressing themes that are of huge importance going forward, including the role of perioperative therapy in squam and the addition of a CTLA-4 inhibitor in Merkel. These oral abstracts are all going to be presented at the 2023 ASCO Annual Meeting. We look forward to seeing you there. So, thank you Jason for taking the time to join us and for highlighting these important advances in immunotherapy. And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode. And finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcast. Thank you for your attention. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers: Dr. Diwakar Davar @diwakardavar Dr. Jason Luke @jasonlukemd Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Diwakar Davar: Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences Consulting or Advisory Role: Instil Bio, Vedanta Biosciences Consulting or Advisory Role (Immediate family member): Shionogi Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences Research Funding (Inst.): Zucero Therapeutics Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy Dr. Jason Luke: Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical , Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof) Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

Spotlight on Immunotherapy at ASCO22

Play Episode Listen Later Jun 23, 2022 27:22

Dr. Diwakar Davar and Dr. Jason Luke, both of the University of Pittsburgh's Hillman Cancer Center, highlight key advances in early phase therapeutics and immunotherapy that were featured at the 2022 ASCO Annual Meeting and also address toxicities, including immune checkpoint inhibitor-associated myocarditis. TRANSCRIPT Dr. Diwakar Davar: Hello, and welcome to the ASCO Daily News Podcast. My name is Dr. Diwakar Davar, and I'm an assistant professor of Medical Oncology, specializing in melanoma and phase 1 therapeutics at the University of Pittsburgh's Hillman Cancer Center. I am the guest host of today's podcast. My guest today is Dr. Jason Luke, a colleague and the director of the Cancer Immunotherapeutics Center at the UPMC Hillman Cancer Center here. Today, we'll be discussing advances in early-phase therapeutics and immunotherapy that were featured at the 2022 ASCO Annual Meeting. You'll find our full disclosures in the show notes, and the disclosures of all guests on the podcast are available on our transcripts at asco.org/podcasts. Jason, thank you for coming on the podcast today. Dr. Jason Luke: Thanks so much for the invitation. It was a great ASCO, and I hope everyone had a good time. Dr. Diwakar Davar: So, onto our abstracts. So, the first one that we'll be discussing, and Jason as you know we've done this before. We'll be rapidly transitioning between phase 1 therapeutics, melanoma, and advanced phase 2 and 3 trials, but you know this is something you do very well. So Abstract 2504, it's a phase 1 trial of TIM-3 inhibitor cobomilab immunotherapy and in combination with PD-1 inhibitors nivolumab and dostarlimab. The AMBER Trial that was presented recently, and in full disclosure, both you and I actually are on this abstract. So, what do you think of this abstract? What do you think of the data that is discussed, and how do we contextualize this in relation to what needs to be done in this space? Dr. Jason Luke: So, I think this is an exciting abstract because it brings forward what may be the next high-priority immune checkpoint to try to target in clinical oncology. To level-set, I think everybody listening will know about PD-1 and CTLA-4 as immune checkpoints. In the last year, we've had LAG-3 come forward as now a standard of care element of armamentarium in melanoma, and we look forward to further studies of LAG-3 and other tumor types as we think it should be a good partner where PD-1 is otherwise approved. So here now, we hear about TIM-3, which is another negative regulatory checkpoint on a number of different immune subsets. And in this abstract, the antibody targeting TIM-3 was cobolimab. So, TIM-3 is a very interesting molecule. It has, what you might call, pleiotropic effects in the immune system. So, while in the context of this abstract, it was being targeted as another immune checkpoint on T cells, it's important to point out that TIM-3 has other regulatory roles in other immune subsets such as myeloid cells and very particularly dendritic cells, and that's important because it might bring in another element of the innate immune system to try to drive anti-tumor responses. So, it's an exciting target because it might be able to expand the groups of patients who could benefit from immune checkpoint blockade. So, in this abstract, we see initially the phase 1 data of combining cobolimab, anti-TIM-3 with anti-PD-1 of a couple of different flavors. And what you could take from this abstract is that in the phase 1 setting, the drug was well-tolerated and combined well, and had pharmacokinetic properties that would be consistent with what we'd expect for this kind of a monoclonal antibody. I think we have to marry this abstract, which is really the phase 1 data about safety in pharmacokinetic (PK) to another abstract presented in the melanoma session, which showed an expansion cohort of patients who got cobolimab plus nivolumab or dostarlimab. And there we did see a 50% response rate, albeit that there was heterogeneity of patients being treatment naïve versus treatment-experienced. So, what I would say to this on a high level is that I think these data are preliminarily exciting, suggesting that further investigation into TIM-3 may be valuable in terms of expanding the population of patients initially in melanoma, but there will data coming soon in lung cancer and in other tumor types with another novel checkpoint. And I think if we think ahead into the future, the question is probably going to end up being, which combinations of checkpoints for which patients. That's pretty exciting to think about. We've seen a lot of data of PD-1 plus other molecules, and I think some future biomarker stratification really will be necessary to know which patient would benefit the most from which of these combos, but for the time being, this is exciting data to see where the field is going to go over the next couple of years. Dr. Diwakar Davar: Great. And I guess, to your point, one important thing to highlight from the abstract is your point about the role of the different compartments. There was actually a very interesting dose-response relationship with the highest dose of the drug not necessarily being the most effective dose, suggesting that yes, as you escalate, you may have different effects in different compartments, and maybe therefore a broad selection of doses might be required to ensure that you have optimal engagement of the optimal target. So, the next abstract is Abstract 3007. This is the tumor-agnostic efficacy and safety of erdafitinib. So, we now know that FGFR pathway aberrations are found from 77% of all malignancies, FGFR targets are now U.S. Food and Drug Administration (FDA) approved in cholangiocarcinoma with pemigatinib, infigratinib, and as well with erdafitinib metastatic urothelial cancer. We know that these agents are not necessarily effective tests in 1 tumor type because these alterations have risen in multiple tumor types. So, the RAGNAR trial, looking at this across multiple tumor types, what do you make of the interim analysis result presented by Dr. Loriot? Dr. Jason Luke: So, I'd say that this is probably the future of targeted therapy. And so, I think that where we have activity in 1 disease, it's very likely we would have activity in others. So, the author has described this as the largest basket trial of a molecularly defined subset that's been pursued to date. There are upwards of more than 200 patients in the study. I think it's really important, as we think about the data, to realize, though, that all FGFR alterations are not exactly the same thing. And so, in this study, they gave erdafitinib to patients with solid tumors of any FGFR altered status. And so that's FGFR1, 2, 3, 4 mutations or gene fusions. And that's a lot of heterogeneity in there actually. And in this study, there were two-thirds fusions and one-third mutations, mostly in FGFR2 and 3. That will become relevant as we start to think about the results. On a high level, I have to say that it is impressive in pan-cancer fashion, just selecting by FGFR alteration, there's about a 30% response rate observed. I think that no matter what, that's going to be valuable considering these were patients with refractory tumors with 3 lines of prior therapy on median. I think what we need to know more is the breakdown of which specific molecular alteration and FGFR in which tumor types drove most of the benefit. So, for example, in bladder cancer where erdafitinib is already approved, that's almost entirely an FGFR3 fusion setting. So we know the drug is effective there. And so I think there will be a further breakdown of the data. As it matures more, you really start to tease out, is it really the case that any FGFR alteration can be treated or there are some that really ought to be the high priorities that we really ought to be going after. I think it would be remiss not to also note, however, that while there's excitement about this sort of pan-cancer approach, the current generation of FGFR inhibitors are not exactly the easiest drugs to take. And so, the in-class, hypophosphatemia and stomatitis really does lead to dose reductions in a lot of the patients. And I think that that's probably really important to emphasize is that despite the pan-tumor activity, there's still a lot of potential in this field to refine further because it's almost certainly the case that if we had less off-target toxicity, so to say, we could improve the efficacy beyond that 30% that we saw here. All the same, I think this is exciting for the concept of a pan-cancer tumor agnostic sort of approach, and we'll really look forward to more data to come from this study over the next, hopefully, few months. Dr. Diwakar Davar: And I guess 1 corollary to that is that we now need to start looking for FGFR alterations in multiple tumor types. So, tests, tests, tests. All right, Abstract 3004, phase 1a/1b dose escalation and expansion study of the MDM2-p53 antagonist BI 907828 in patients with multiple solid tumors including advanced, metastatic, liposarcoma. So, we've recently had data of the previously undruggable KRAS, and now we've got previously undruggable p53, for which we now have targets. So, Jason, what do you make of the p53 targeting approach, in this case, using MDM2 and this particular drug from Boehringer Ingelheim? Dr. Jason Luke: So, I think that this is an exciting abstract exactly for the reason that you mentioned, which is that p53 has been, and unfortunately, to some degree, still remains, one of those holy grails but undruggable targets in oncology. So MDM2, for those who are listening but might not be aware, is a negative regulator of p53. So, the concept here then is if you drug it, you might release p53 to reactivate activity in that pathway, and then p53 being the guardian of the genome, so to say, potentially leading to apoptosis of cancer cells. And so, this drug binds MDM2 and MDM2 can be amplified as a resistance mechanism in p53 and several tumor types. And so here, they showed data for the early part of a clinical trial investigating the small molecule, BI 907828, but then they focus specifically in liposarcoma, which is a disease known to be an MDM2 amplified. And so, the results were pretty interesting. The toxicity of this kind of an approach, just to note, is really in class. It leads to some gastrointestinal (GI) toxicities as well as hematologic problems, and this goes again for most regulators of the cell cycle will have these effects, whether they're CDK inhibitors or MDM2 or p53 modulators. But I think what was very interesting, this is a disease liposarcoma where chemotherapy, functionally speaking, has no role. We, unfortunately, give it to some patients sometimes, but it has almost no activity, and they observe that in poorly differentiated liposarcomas, the response rate was about 12%, but the stable disease was quite durable. And so, I think that really is potentially a big deal because this is an orphan disease. It really lacks any other treatment. But as you zoom out from that, if you start to think about targeting amplified MDM2 in other settings, I think the activity that we see here is intriguing, and potentially suggests that we may be coming to a future where we'll have multiple, sort of, orthogonal approaches after reactivating p53. There were actually other abstracts at ASCO Annual Meeting of other molecules that were less mature also along this line. So, I think, very exciting to take away from this, one, a potential treatment for liposarcoma for all of those patients that anybody listening actually sees, but secondarily this concept of targeting p53, which I think we'll see a lot more of over the next couple of years. Dr. Diwakar Davar: Excellent. Moving on to the Abstract 3002, this is a phase 1, two-part multicenter, first-in-human study of DS-6000a of an antibody-drug conjugate comprising the anti-CDH6 IgG1 monoclonal antibody that is attached to a topoisomerase I inhibitor payload via a cleavable linker. And so basically, a way in which you can give topoisomerase: (1) TOP1 inhibitor, (2) CDH6-expressing cells. This was studied in advanced renal cell carcinoma (RCC) and advanced ovarian cancer in this abstract presented by Dr. Hamilton. Jason, what do you think of the results and what do you think of this approach in general, this antibody-drug conjugate (ADC) approach using novel targets as well as novel payloads? Dr. Jason Luke: I think this is one of those that you can't help but be pretty excited about, and I think in the context of the data shown at the plenary session in breast cancer for antibody-drug conjugates (LBA3), I think this is really where the field is going to start to go. So, you mentioned that this is an antibody-drug conjugate that targets cadherin 6 or CDH6, which people will remember from biochemistry class and medical school, or something is a cell-cell adhesion molecule, really a basement membrane protein. So, the concept of targeting it really is just to go after a latch mechanism to get the molecule into the tumor where you want. And CDH expression is very high in renal cell carcinoma, upwards of 80% of samples, also high in ovarian cancer, which is why they chose those 2 tumors to go after. So, the ADCC, and you described its structure just a little bit, but it's essentially the same backbone as trastuzumab deruxtecan, which we saw this outstanding activity for HER2 and breast cancer on the plenary, with these 8 chemotherapies moieties attached to it, but here now, targeting it instead to HER2, with this molecule now to CDH6. And I think, again, you can't help but be impressed. There were treatment responses on almost every dose level of the dose escalation in this study. There's in fact only 1 patient whose tumor was not, at least, stable disease or a PR, and I think that that just goes to show the power of truly bringing the chemotherapy in a targeted manner into the tumor microenvironment. Responses were heterogeneous. They were not super deep responses per se, but the stable disease was quite durable in the study, and the patients were going out more than 7 months. And again, realizing this is at the lower dose levels as we're increasing the dose and move this in their earlier lives of therapy is likely to be even more effective. They did show a waterfall plot of the reduction in CA 125 for the patients with ovarian cancer that really looked quite impressive. And given that that's our clinical biomarker that we commonly follow, it may actually even more indicative of the benefit we would see as opposed to resist. Now, again, there is some toxicity. It is a chemotherapy moiety that's conjugated to the ADCs. So, the most common toxicities were nausea, vomiting, and low platelet counts, but these are kind of toxicities that we're quite accustomed to with chemotherapy. Just to summarize, I think there's a lot of promise for this kind of antibody-drug conjugate targeting, and I think it can only be impressive that they had this amount of activity in the dose escalation of the study. [I] very much look forward to the expansion cohorts in renal and ovarian, which we'll presumably expect to see later this year, early in the next year. Dr. Diwakar Davar: And as you alluded to, this really was parallel that ASCO, by the standing ovation given to Dr. Modi when she presented the DESTINY04 data of trastuzumab deruxtecan in HER2-low breast cancer, basically now redefining breast cancer from 4 camps, now we have to think of not just HER2 amplified or HER2-high, but also HER2-low. So yes, really have to now rethink how we classify these diseases (LBA3). So Abstract 2509, the efficacy of anti-PD-1/PD-L1 immunotherapy in non–small cell lung cancer dependent based on CD8 and PD-L1 status. So really Dr. Galon taking us into what he has now described as the immunoscore—really a way of characterizing tumors. A way of thinking about tumors that you've also championed, Jason, in terms of this T cell-inflamed and uninflamed hypothesis. So, tell us a little bit about how these jives with your work and how you would think about lung cancer patients responding and not responding to immune checkpoint inhibitors (ICI) therapy in this context? Dr. Jason Luke: Yeah. I think the focus quickly here on the immunoscore, so the people are aware of that, I think is really important for diving into these specific results. You have to realize our fundamental underlying predicate for immune checkpoint blockade inhibitor response is that patients have mounted an adaptive immune response. So, CD8 T-cells have gone into the tumor where they elaborate chemokines and cytokines like interferon gamma, which upregulates the expression of PD-L1 in the tumor but also in the surrounding immune cells. So, you realize that even though antibodies are targeting PD-1, it's really that we're targeting that tumor microenvironment. So, the more robustly we can measure that, and we understand it, the more likely we are to know whether or not the patient is going to benefit. So, this is where the immunoscore comes in. The immunoscore is actually a fairly simple test. It's one slide, immunohistochemistry slide where they can stain jointly for CD8 and PD-L1 on the same slide. And that allows them to do a number of different things beyond just testing the total level of PD-L1. They can test the CD8 density, the PD-L1 expression, but then also the interaction between CD8 T-cells, their distance from each other, from PD-L1 expressing cells, and so on and so forth. And so really [this] can give us a much more robust analysis of what all is going on in the tumor microenvironment again, off of a single slide. So here then, in this abstract, for patients with non–small cell lung cancer receiving anti-PD-1, they then compared the utility of only PD-L1 testing versus doing the immunoscore. And so, it was actually quite a large set. They had about 250 patients in their analytical set and then split about 150 or 180 or something into the training and validation sets, and they compared the immunoscore against 2 different standard PD-L1 antibodies, the 22C3 as well as the SP263. And what they saw was a high concordance for expression between PD-L1 and the immunoscore. That's good, because, again, they're measuring PD-L1 in both of those. And so that was a good, sort of, level set. The immunoscore, however, allows them to look to 7 different parameters, again, beyond just PD-L1, as I mentioned. So, CD8 density, interaction, distance, and this kind of thing. Then in these test and training cohorts, they were able to actually split out patients who are PD-L1 positive into further groups, those that were immunoscore low and that were high. And in so doing, they were actually able to sort of dramatically predict the likely progression-free survival on PD-1 checkpoint blockade in those different non–small cell lung cancer groups. So why is this important? Selection of patients by PD-1 has been very useful in the field of non–small cell lung cancer, but it's hardly a panacea. You're not at all assured your patient is going to do well just because they're PD-L1. And here comes a second assay that can be done in a standard of care setting. So, the immunoscore is a test. You could just order it, and that really does give you much more predictive power about who's likely to do well and who isn't. And I think this test and more broadly multi-spectral imaging is really going to become a core component to how we risk stratify and predict outcomes to checkpoint blockade and lung cancer, but broadly in other tumor types over the next couple of years. Dr. Diwakar Davar: Okay. Now, moving on from a biomarker for PD-L1 and PD-1 to a setting in which PD-1 was just recently U.S. Food and Drug Administration (FDA)-approved, so I'll give a brief background to the trial that you've actually developed and led. And so, this is KEYNOTE-716, the abstract in question is LBA9500 (late-breaking abstract) 9500, but this is the distant metastasis-free survival (DMFS) data readout. The DMFS, distant metastasis-free survival with pembrolizumab versus placebo in the adjuvant setting for patients with stage IIB or IIC, that is high-risk node-negative melanoma and the data from the phase 3 KEYNOTE-716 study. So, this data, at least the recurrence-free survival (RFS) data was actually earlier published, you had presented it earlier last year and also more recently this year, but it was published recently in Lancet. And we know that 716 is a study in which, for the first time ever, we have an immune checkpoint inhibitor PD-1 that was studied against placebo with the high-risk node-negative setting in stage IIB and C melanoma, demonstrated a significant RFS benefit in the setting against placebo. And now we have the DMFS readout. Maybe you could tell us a little bit about both the RFS and the DMFS data, and why this is such an important advance for these patients. Dr. Jason Luke: Thanks. And I agree this really is a sea change in how we thought about stratification of patients with melanoma, but I think this broadly has implications for other tumor types as well. So, in melanoma, we've historically thought of its involvement of the lymph nodes—stage III as being the high-risk disease, but we also, if you look at the outcomes from the AJCC, we see the patients with stage IIB and IIC, so deep primary lesions, actually have similar bad outcomes as those patients with stage IIIA and IIIB. And so anti-PD1 and adjuvant therapy and melanoma were originally proved for stage III, but having understood that about 5 years ago actually, started to think, well, why not also treat the patients with stage II if they're at similar risk. And we pursued KEYNOTE-716 as you mentioned, and it read out last year as a positive trial for recurrence-free survival. And the abstract here then was to look at the impact on distant metastasis-free survival. So, while the regulatory consideration for approval, and it is approved and it's available for patients now, was based on relapse, what we really want to be preventing is the development of metastatic disease because presumably that would correlate with the eventual death of the patient from cancer. So, in the abstract here, we see the first update for DMFS, which also was positive on its first analysis, the hazard ratio at 0.64. And so, again, very similar to the RFS benefit, showing about a 35-36% reduction in distant metastasis-free survival. And this is a theme that we've seen across adjuvant studies in melanoma, all the adjuvant studies in fact, is that the RFS improvement, the relapse-free survival hazard ratio mirrors very closely the distant metastasis-free survival ratio. We saw that again here. I think it just emphasizes that anti-PD-1 immunotherapy is highly effective in melanoma no matter what stage it's in, but rather related to the risk of death for melanoma. And so this really has a practice changing in the field of melanoma oncology. Patients need to be referred to medical oncology early for discussion around risk stratification and consideration of adjuvant therapy—I think even at the same time that they're having resection of their primary lesion, and it even calls into question of whether or not we should even fully be doing procedures like sentinel lymph node biopsies any longer, considering we can make the decision to give adjuvant therapy now based on the primary—albeit that's a controversial area of discussion. And I would just love for this to start to penetrate into other disease settings. We've seen more recently, approval for neoadjuvant therapy in lung cancer and we see in kidney cancer, bladder cancer. We see adjuvant therapy in—I think we're going to see immunotherapy starting to become an important part of the armamentarium in these hard-to-treat cancers, even at the time that perioperatively before or after surgery. So definitely a major change in the way we're thinking about stratifying patients and emphasizes that you need to get those patients with melanoma in to have that discussion around adjuvant therapy probably at the time of the primary lesion resection. Dr. Diwakar Davar: And finally, Abstract 2507, single-cell profiling of human heart and blood in patients with checkpoint inhibitor-associated myocarditis. So, this is data from the NGH Group, Dr. Villani and colleagues are presented by Dr. Blum. We know that myocarditis is an uncommon but very serious immune related adverse event (irAE), and here in this particular dataset, this group which has done a lot of underlying work to really uncover the role of certain key phenotypes, cellular phenotypes, in the development of myocarditis it's presenting the data in the context of ICI-related myocarditis. So, what do you think of this data, what do you think of the use of checkpoint inhibitors are now, as you've said, migrated linear in the lifecycle of the patient, what do we need to be thinking about and how does this improve our understanding of both the use of the drug and what we need to be worried about? Dr. Jason Luke: I think the toxicities of immunotherapy, while, less frequent than, say, chemotherapy, can actually be more disastrous. In the rare patients, we have extreme immune-related adverse events, there is an incidence of actually life-threatening and fatal events. And so, myocarditis, associated with checkpoint blockade, is one of those things that could be seen, and here at ASCO Annual Meeting, we saw a couple of abstracts summarizing the experience from the National Cancer Institute following myocarditis events, and then this abstract in a translational level trying to better understand what is actually going on in terms of the immune response in those myocarditis cases. And so, I thought this was actually a very interesting abstract. There was only a small number of patients. They had 13 samples from patients who had had endomyocardial biopsies in the context of immune-related myocarditis, and you might say, well, only 13 samples, but fortunately, this is quite a rare event, less than 1% of patients who get immune checkpoint inhibitors. And what they saw was relatively unsurprising, which is that in patients who were having myocarditis, they saw an increase in T cells and in K-cells, as well as activated CD8 and CD4 T-cells. I think what was very interesting was when they started to dig into what were the phenotypes of the cells and what were the pathways that were turned on. Again, it was not especially surprising to see that they saw increased levels of interferon signaling and immune-receptor signaling as well as motility and adhesion, but this really, I think emphasizes that there are potentially interventions beyond just the general immune-suppression approaches that we give. They could be more nuanced but perhaps more efficacious because sadly, patients do pass away when they develop this. And in their cohort of 13 patients, 3 of those patients died. And specifically, in looking in those 3 patients, they actually saw that all 3 patients had a shared T cell cluster. And they can't exactly say what it is exactly yet, but I think it's very interesting to see that because it suggests that there's probably something about the T cell response in those patients that disproportionately triggered a fatal event. And if we can understand that better, we then may be able to really tailor our interventions in a way that is more useful. Because, frankly, the way these patients usually present is they show up in the emergency room (ER), and they're seen by an ER doctor who thinks they're having acute coronary. They ship them off to the catheterization (cath) lab. They open him up, and then they get in there, and there's nothing going on. There's no plaque. And so now, all of a sudden, everyone is quite confused. And so, if we had better ways to search for that ahead of time to be aware of it, we might have better interventions because usually what happens right at that moment is everybody gets very confused and starts calling the oncologist, and we start slapping on steroids and other immunomodulatory agents, but sometimes it's late. So, I think this is a great abstract. It's really starting to preliminary give us an idea of what is the actual biology that underpins these terrible events, and we can hope that we can build off that over time hopefully to eventually come up with better predictors and then obviously better interventions to try to avoid these outcomes in a small but real number of patients. Dr. Diwakar Davar: Excellent. One other point is you and I are both involved in drug development, and as we start thinking of side effects. Side effects are really on the flip side of responses in drug development. So really 1 point to make of this is that when people start developing side effects rather than, as you say, putting your hands up in the air and waving them around, 1 of the things that we should be doing in drug development is possibly biopsying these patients because we could get new PD insights into how these drugs work, why they work, and particularly which sub-populations themselves they work on, particularly in the early-drug development setting when you oftentimes don't have that many responses. With that, thank you, Jason, for sharing your insights with us today. Dr. Jason Luke: Thank you. Dr. Diwakar Davar: And thank you to our listeners for your time today. If you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. So, thank you for your attention, and we will sign out. Disclosures: Dr. Diwakar Davar: Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences Consulting or Advisory Role: Instil Bio, Vedanta Biosciences Consulting or Advisory Role (Immediate family member): Shionogi Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences Research Funding (Inst.): Zucero Therapeutics Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy Dr. Jason Luke: Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical , Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof) Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

university ai pr moving travel food spring er patients hamilton pittsburgh consulting stock pfizer selection keynote responses bi gi werewolf relation pd immune bayer ds pk abstract modi oncology ici merck endeavor lancet patents janssen blum ragnar novartis top1 royalties lag accommodations immunotherapy gsk asco genentech national cancer institute disclosures drug administration fda abbvie stipe bristol myers squibb takeda adc regeneron rcc adcc her2 villani boehringer ingelheim gilead sciences kras adverse events medical oncology cdk loriot rfs nektar onc adcs prognostic cancer immunotherapy pd l1 eisai asco annual meeting iic iiib iib pyxis rubius servier cd8 t cd8 ctla cd4 t emd serono incyte pd1 iiia alnylam fgfr genmab moderna therapeutics ajcc mdm2 shionogi tesaro jason luke transcript dr array biopharma synlogic fgfr1

ASCO22: Key Posters on Advances in Immunotherapy

Play Episode Listen Later May 27, 2022 21:37

Dr. Diwakar Davar and Dr. Jason Luke, both of the University of Pittsburgh's Hillman Cancer Center, share the latest news on immunotherapy trials KEYNOTE-A10, LIBRETTO-001, and other key IO studies across tumor types featured at the 2022 ASCO Annual Meeting. Transcript Dr. Diwakar Davar: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Diwakar Davar, and I'm an assistant professor of Medical Oncology in phase 1 therapeutics, at the University of Pittsburgh's Hillman Cancer Center, and the guest host of today's podcast. I'm delighted to welcome Dr. Jason Luke to this podcast. He's the director of the Cancer Immunotherapeutic Center at the Hillman Cancer Center, University of Pittsburgh, and a great colleague and friend. Today we'll be discussing some key posters that highlight some advances in immunotherapy that will be featured and the 2022 ASCO Annual Meeting. You will find our collective disclosures in the show notes and the disclosures of all guests on the podcast are available on our transcripts at asco.org/podcasts. So, Jason, thank you for coming on the podcast today. Dr. Jason Luke: Well, thanks very much for the invitation. I always love doing these podcasts for ASCO, and never love anything more than hanging out with my friend Diwakar Davar. Dr. Diwakar Davar: Well, thank you! Below are the abstracts we've selected. We will start with Abstract 2504. This is a phase 1 trial of the TIM-3 inhibitor cobolimab monotherapy, singly and in combination with the PD-1 inhibitors nivolumab or dostarlimab. Phase 1 data from the AMBER trial with the presenting author being Dr. Gerald Falchook. And this is a trial that initially started several years ago. And I know Jason, that you were involved with the inception of this agent, that TIM-3 inhibitor. So, walk us through, TIM-3. It's a third-generation checkpoint, we now have TIGIT LAG coming into the landscape. Definitely a first indication for LAG-3 melanoma with a positive trial, RELATIVITY 047. So, where are we with TIM-3? Why should we be excited about TIM in general, and this data in particular? Dr. Jason Luke: It is quite exciting, especially building off the recent data that we saw for relatlimab or LAG-3 because it's becoming clearer that a number of these other immune checkpoints that we have been talking about for many years, actually really can be effective when used in the right setting. So, this drug, this anti-TIM-3 antibody cobolimab monotherapy, as you mentioned, started out in a phase 1 clinical trial dating all the way back to I think about 2015. And that was at the time in immuno-oncology when everybody was so excited, [and] they thought everything was going to work immediately. Subsequent to that, obviously, we've had some hurdles that we've had to come over. But we're coming back to some of these agents now, which are looking very exciting. So, just in the same way we think about blocking PD-1 or now blocking LAG-3 to reinvigorate T cells in the tumor microenvironment, there's a good chance and a high probability based on preclinical data that blocking TIM-3 could be just as effective as blocking LAG-3, so to say. Now, one thing that I note in this abstract is really the safety finding and early PK analysis. And so, this is the important work we do early on to understand the drug. It's important to be aware that in a study like this, it's very hard to seek efficacy signals. So, when you see this poster, really, you probably shouldn't be thinking, ‘Oh, this is a frontline phase 3 trial,' but rather that the efficacy is going to be a secondary consideration. Rather, what's quite important is looking at the properties of the drug and looking at the safety signals around that. And what we can see here is that TIM-3 appears to be quite safe when blocking it in conjunction with anti-PD-1 across several different tumor types. And that really sets the stage then to think about moving this into earlier lines of therapy across many different cancers. And so, here we see advanced solid tumors but focused on lung cancer and melanoma and kind of the usual tumors we think about, and people can keep their eyes open because there are other posters of this molecule with PD-1 in some of the other sections outside of developmental therapeutics. Now, one thing I would like to get your opinion on because your group has focused a lot on TIM-3, as I described it as this T cell centric mechanism to reinvigorate exhausted T cells. But it's possible that TIM-3 does other things as well. And I don't know if you want to comment on that or give any other feedback that you've had when thinking about this AMBER Trial. Dr. Diwakar Davar: That was an excellent summary, Jason, of really what is a truncated 8-year track record of developing this agent all the way from 2015. But you bring up a very interesting point, which is: exactly what does this drug does in the non-T-cell compartment? Some very interesting data from Brian Ruffell in a paper that was published about 3 years ago now suggested that TIM-3 was actually potentially a myeloid checkpoint, meaning that, in a tumor model in which Dr. Ruffell was studying this in the context of breast cancer, the drug primarily appeared to work on the effect of antigen-presenting cells and augment the presentation of antigen to T cells suggesting that it may be, in addition to being a chronicle T cell exhaustion marker, it may also be reinvigorating antigen-presenting cells. And the question of whether or not the role of TIM-3 on APCs as well as the role of TIM-3 on T cells, and which of these compartments are more important, and how these compartments segregate in any given cancer across many different lines of therapy will hopefully be something that we disengage, and understand a little bit better as we look at biomarkers of this drug across different settings. And especially to that point, Jason, the biomarker question, you'll notice that very interestingly, that was a signal in which that drug had a certain response rate. Again, as you correctly point out, we cannot read too much into response rates in very small patient numbers. But very interestingly, there was a slightly higher response rate at the 300 milligrams, which is not the top dose level of the drug, and a slightly lower response rate at the ceiling dose of the drug that was tested, 900 milligrams, leading the investigators to conclude that the RP2D, was actually 300 milligrams every 3 weeks and not 900 milligrams. What are your thoughts on dose in the context of immunotherapy (IO) drug development? And why might it be that 300 is the optimal dose as opposed to 900? Dr. Jason Luke: That's a complicated question. I mean, when we think about checkpoint blockade, we classically think about it as only blocking on T cells. But to your point, if there are multiple mechanisms in play, sort of modulating other cell compartments actually may start to do different things at different doses that maybe weren't our primary intent as we went into the trial. That's a little bit of hand waving, immunologic hand waving, but I think the data are the data and once we hit an effective dose level, there's really no need to really push the dose that much further. But that really emphasizes the importance of these kinds of early phase clinical trials. So, I'm really looking forward to seeing this data. For disclosure, obviously, we have both been investigators on this trial. But we're very excited about the idea that there may be hope for a fourth checkpoint to come forward in the field beyond just PD-1 CTLA-4, and LAG-3, maybe now here with TIM-3. Dr. Diwakar Davar: So, with that we'll go to the next abstract and that is Abstract 2516, “Phase I trial of adjuvant autogene cevumeran, an individualized mRNA neoantigen vaccine, for pancreatic ductal adenocarcinoma.” So, this is an mRNA vaccine from our good friend, BioNTech. And that's been essentially evaluated in the context of highly lethal cancer, pancreatic ductal cancer, and specifically in the context of adjuvant vaccines, specifically in the setting of patients who had followed definitive pancreatic cancer surgery. So, Jason, you know a lot of neoantigen vaccines, you've led some of these trials, really, the neoantigen vaccine is really the primary reason we are actually having an in-person meeting this year, because if not for this company and others like this, really this pandemic would not be behind us. What are your thoughts on the role of neoantigen vaccines in cancer therapeutics, and also, particularly this particular trial in the data, the immunological data, and the clinical data regarding the development of neoantigen-specific T cells in this setting, and what this means for you? Dr. Jason Luke: Right. So, the idea of targeting neoantigens as cancer immunotherapy was really all the rage a few years back, and it was thought based on preclinical animal models that this was just going to be the secret sauce, and this would be the new targeted therapy for immunotherapy. And it isn't to say that that's not true, but the first generation of neoantigen, peptide-based vaccines for the most part, unfortunately, just kind of didn't end up moving the needle the way we had hoped. The question then was raised: is that because targeting neoantigens isn't reasonable, or is that because the setting where we were trying to do it in the refractory disease area was not the optimal way to leverage this? And so, a couple of different companies and trials now are coming forward looking at targeting neoantigen in a minimal residual disease setting where the idea could be that immunologic responses that you could generate wouldn't be hampered by all the immunosuppression associated with the tumor microenvironment. And so, here we have this molecule, which you eloquently pronounced, ‘autogene cevumeran.' It's an RNA-lipoplex neoantigen vaccine. So, it's not a peptide. It's more like the COVID-19 vaccines actually. And it's being given after surgery, followed by anti-PD-L1 followed by chemotherapy. So, it's a complicated regimen, but it's very intriguing these early data, which do show that the patients who got the vaccine seemed to have better and longer-term outcomes. But then as you emphasize, really, I think probably what's at the heart of this that really makes it exciting is their ability to immune monitor the patients, meaning to look for antigen-specific immune cells from the peripheral blood in these patients to be able to identify those immune responses as being specific to cancer. Because this kind of a clinical trial, it's still signal seeking and proof of concept kind of trial. In order to actually establish that a vaccine approach in a post-surgical setting would have efficacy, we need to do a large randomized trial. And so, this is not that yet. But I think these data really point in the direction that that could be a reasonable thing to try. And when you think about pancreatic cancer, where we've made no success with immunotherapy, really in a meaningful way in terms of checkpoint blockade, at least, that's pretty exciting actually to think about. I would actually marry this dataset with another that we actually saw at the American Association for Cancer Research (AACR) meeting that also looked at neoantigen targeting and antigen-specific responses in colorectal cancer, again, and in a similar setting with the minimal residual disease setting. And so, I think this highlights that we may need to start thinking about using immunotherapy in different ways than we had before. Obviously, everybody knows about using PD-1 blockade in lots of different cancer types that are really for metastatic disease, or maybe even for adjuvant now in melanoma a little bit. But maybe there's this space, which is the minimal residual disease setting where you might be able to detect by ctDNA after surgery, the patients are still positive. And maybe you could treat that before there's visible cancer, and maybe certain immunotherapies could be more valuable in that setting than others. And that's where I think maybe some of these mRNA technologies really might find their sweet spot. So, coming back to this abstract, I think really, the emphasis point here is the novelty of generating patient-specific neoantigen vaccines, and then being able to track linearly over time the immune response against those vaccines. I think with that kind of technology and being able to leverage that, I think we're really headed towards a real shift in the way we think about managing cancer in a post-surgical setting, again, thinking about MRD, or minimal residual disease, maybe in a way that our leukemia colleagues have been thinking it about for a long time. Dr. Diwakar Davar: That's an excellent summary of a very, very complicated, both setting, and in this case, a therapeutic landscape. So, well said, well summarized, and we'll now pivot to Abstract 2514. So, this is ‘Efficacy and safety of NT-I7, long-acting interleukin-7, plus pembrolizumab in patients with advanced solid tumors: Results from the phase 2a study' [and] the presenting author is Dr. Aung Naing from [The University of Texas] MD Anderson [Cancer Center]. So, Jason, you know, with checkpoints, we've got so many thoughts about checkpoints, particularly given the rather unfortunate failure of BEMPEG in the context of melanoma. So, we've got lots of interesting cytokines that we think of as important in the context of immuno-oncology 2, certainly 12, 15. You've been very involved with IO-15. We've got a lot of clinical trials studying IL-12. And now we've got one studying IL-7. So, tell us what do you think of this IL-7 targeting approach in the context of cytokine-based therapeutics? Dr. Jason Luke: I think it's really important to emphasize on first principles, for those that are listening, who don't think about immunology all the time that not all cytokines are the same thing. So, interleukin 2 that many people have heard of is very different actually than interferon. And that's very different from many of the other cytokines, the ILs, and everything, right? So, IL-7 is a very potent cytokine that's associated with the expansion of immune responses, and that can drive interferon gamma-dependent effects. And you should hear whenever I say interferon-gamma is sort of a link through to PD-1 responsiveness. Because we think the mechanism that underpins anti-PD-1 effectiveness in patients really is interferon gamma biology. So, IL-7 has been a molecule, it's been of a lot of interest but really was too toxic to try to deliver. But now we have novel drug delivery sorts of approaches that are being developed to try to bring the drug in, in a way that doesn't cause such systemic toxicity. So, in this clinical trial, this NT-I7 molecule is given intramuscularly, every 6 weeks in conjunction with pembrolizumab, and very interestingly, in a small number of patients, but there were resist responses observed across a series of tumors that you really wouldn't expect should be responsive in any way to pembrolizumab alone. And so, we're talking about microsatellite stable colorectal cancer, pancreatic cancer, and some others as well. And in conjunction with that, they were able to identify some of the biomarker effects we would think we would see with IL-7, such as expansion of peripheral immune compartments. And the toxicity profile was really consistent with what we've seen with fevers and chills, but manageable in a way that previous approaches really weren't. So, I think this is really exciting because I think the idea here then is with this IL-7 approach, we might expand the kinds of cancers that we could go after, in conjunction with anti-PD-1 again, pancreas, colorectal cancer. I think that's really where the unmet need lies in oncology. So, I really applaud these kinds of approaches and several of these cytokine approaches, and what we're going to talk about them, I think, have the potential to do that over the next couple of years. Dr. Diwakar Davar: Excellent! Pivoting now to a different cytokine, but one that was alluded to before IL-12. So, Abstract 2518 is ‘Phase II evaluation of the combination of PDS0101, M9241, and bintrafusp alfa in patients with HPV 16+ malignancies,' and the presenting author here is Dr. Julius Strauss of the NCI Cancer Center and the Clinical Center of the National Cancer Institute at the National Institutes of Health. So, what do you think, Jason, about the role of the HPV targeting vaccine, in this case, that was added to IL-12 immune-cytokine and bintrafusp alpha contextualizing the recent data that we have of bintra along with what is a very interesting result here? Dr. Jason Luke: Yes, I think building on the last abstract where we talked about IL-7 as some novel biology now we move to IL-12, which again introduces other biology. So, interleukin-12 is a complicated cytokine, but one that's strongly associated with initial immune responses or immune priming, as well as enhancement of anti-tumor effects in the tumor microenvironment. So, here we have sort of a 3-legged approach. So, the vaccination approach against HPV really can generate a strong immune response initially, and that can be supported with the IL-12. And then you come in with anti-PD-L1 and to whatever extent the TGF data is relevant here. And so, you have this cocktail where you're generating tumor-specific responses with a vaccine, you're supporting them with IL-12, and then blocking PD-L1. And as we go back even a couple of abstracts we talked about, now we sort of have a cocktail right of approaches. And so, I think this is very exciting. It's unique in that, in these tumors, obviously, HPV is the driving force of cancer. So, developing a vaccine against that is fairly straightforward. But I really like this concept of bringing forward sort of a multi-dimensional immunotherapy approach. And we'll note they have previously presented data on this trial, I think last year at ASCO, actually. But what they see are pretty strong response rates, almost 30% range in PD-1 refractory tumors. Again, that's our area of really high unmet need. It's hard to read through how useful a PD-1 naive treated patient here, although the response rates were high. But to me, it's really those patients who had progressed on PD-1 where they're getting these responses that tells me that this really could be something that's useful and potentially could be expanded beyond just say head neck cancer to any HPV relevant malignancy. Dr. Diwakar Davar: Excellent! Now on to our last abstract. Abstract 2520, ‘Effect of intratumoral INT230-6 on tumor necrosis and promotion of a systemic immune response: Results from a multicenter phase 1/2 study of solid tumors with and without pembrolizumab (PEM) [Intensity IT-01; Merck KEYNOTE-A10].' The first author is Dr. Jacob Thomas. Jason, we've seen a lot of interesting intratumoral therapies. You and I have both done a lot of studies in looking at intratumoral agents from toll-like receptor agonists, TLR-9, TLR 7-8, and more recently, oncolytic viruses. So, contextualizing IT230-6 in the spectrum of intratumoral therapies, how do you feel about this drug, which is actually a very interesting novel drug. It's not just a TLR agonist, or for that matter, an OV, very interestingly, it's an intratumoral therapy that has actually got chemotherapy in it. So, how do you feel about this drug? How do you feel about the responses that we've seen? And particularly how do you feel about the setting in neoadjuvant breast cancer? Dr. Jason Luke: Yeah. I would pick up where you said that this drug INT230-6 is just a really interesting concoction. So, it's cisplatin mixed with vinblastine, in a specific amphiphilic molecule that allows it to diffuse in through the cancer. And so, if you had said that to me a few years ago, I would have looked at you and been like, ‘What are you talking about?' But I think the data that's been emerging for this is just really interesting because something about this chemotherapy cocktail actually drives immune responses. And really what the focus of this abstract is on is showing that you get an influx of CD foreign CDTa cells into the tumor microenvironment that's associated with a therapeutic benefit. I think that's just really, really interesting to think about. It sort of makes one wonder when we're doing these intratumoral injections, how much of it is just the injection, and how much of it is the therapeutic agent, but I think it's a really novel therapy, and one that appears to be very well tolerated as well. And that's also the exciting part. When you hear cisplatin and vinblastine, you think, ‘Oh, well, that's not going to work.' But apparently, it stays right in the tumor and generates these immune effects. I think it's very exciting. I think their approach here—going after what we usually call cold tumors, ones that don't respond to immunotherapy, you mentioned breast cancer—I think it's really interesting. I'm really looking forward to seeing the actual data from this abstract because, on first pass, it wouldn't have been what I thought about in terms of driving immune responses, but maybe it just goes to show that there's a lot more to understand there about immunogenic cell death and some of these other concepts that we bandy about. But I think this will be one of the most interesting abstracts actually to see the data for once it's available. Dr. Diwakar Davar: Great! Taking a slight pivot from that. You've been involved in the development of novel response endpoints. One of the issues that we have with intratumoral therapies is that you're measuring a lesion that you inject, so now you inject something and it gets a little bigger. Is it getting bigger because it's growing? Is it getting bigger because the drug is working? We don't know. We have now itRECIST, which you have been working on. What's very interesting is that whether you look at itRECIST, or RECIST, irRECIST, or imRECIST, when you have the monopoly of different response endpoints we have to deal with these days, these patients have monotherapy responses in non-injected tumors. How do you feel about that as a drug developer and somebody who's giving patients drugs like that? What is your impression of having shrinkage in the non-injected tumor? Dr. Jason Luke: I think it's really exciting about this concept of the abscopal effect that we've bandied about for years. Despite being an investigator in this space, I'm really excited to actually see the data and to understand what these out of field responses are. If it's really true that this is robust, I mean, it could potentially be like a game-changer kind of thing. But I'll reserve judgment until I see the actual scans of the tumors that actually shrank that weren't injected. Dr. Diwakar Davar: Fantastic insights, Jason. So, thank you for taking the time to join us on this podcast and to highlight these extraordinarily important advances in immunotherapy. Dr. Jason Luke: I appreciate the opportunity to participate today. Dr. Diwakar Davar: So, thank you, and thank you to our listeners for your time today, you will find the links to the abstracts that we discussed today in the transcript of the episode. Finally, if you're enjoying the content on the ASCO Daily News podcast, please take a moment to rate review and subscribe wherever you get your podcasts. So, thank you, Jason. And thank you to the team for putting this together. Disclosures: Dr. Diwakar Davar: Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences Consulting or Advisory Role: Instil Bio, Shionogi (Immediate Family Member), Vedanta Biosciences Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, Zucero Therapeutics (Inst), GSK, Merck, Arcus Biosciences Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231, and Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy Dr. Jason Luke: Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, Stipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences , Hotspot Therapeutics, SERVIER , STINGthera, Synthekine Research Funding (Inst): Merck, Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma, EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof) Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

covid-19 university health ai travel spring pittsburgh phase cd consulting stock results pfizer national institutes ils pivoting werewolf relation io advances american association mrna pd immune bayer pk abstract oncology hpv merck rna endeavor efficacy patents subsequent janssen novartis relativity posters royalties lag ov accommodations immunotherapy cancer care gsk asco genentech national cancer institute disclosures mrd phase ii abbvie stipe bristol myers squibb takeda regeneron gilead sciences adverse events medical oncology nektar tlr texas md anderson cancer center onc libretto prognostic cancer immunotherapy pd l1 tgf eisai asco annual meeting pyxis rubius servier ctla ctdna apcs emd serono incyte alnylam genmab jacob thomas moderna therapeutics clinical center cancer research aacr tesaro jason luke transcript dr recist arcus biosciences array biopharma cdta synlogic

Radu Tesaro se proslavila svými barevnými obrazy afrických zvířat

Kavárna

Play Episode Listen Later Nov 21, 2021 15:10

Naše klidné posezení v Kavárně vám přinese tip k poslechu audioknihy Sedmilhářky, nebo k zalistování komiksem, který v sobě spojuje lásku k hokeji a filmu. Ale ze všeho nejdřív se vypravíme na vernisáž. Malířka Radka Tesařová, známá spíš pod uměleckým pseudonymem Radu Tesaro, se proslavila svými barevnými obrazy afrických zvířat - slonů, leopardů nebo lvů. Ovšem poté, co opustila Afriku a přesídlila do jižních Čech, objevuje se v její tvorbě i česká krajina.

ale ov radu xed xe1 obrazy zv xed proslavila tesaro

Interview With Tokens.com CEO

Moon Or Bust

Play Episode Listen Later Sep 30, 2021 60:22

Subscribe to our Benzinga Crypto Youtube Channel Episode Summary:Cardano Smart ContractsArbitrum and L2sWalmart and LTCTokens.com InterviewMoon or Bust - To Play Moon or Bust go to https://www.benzinga.com/markets/cryptocurrencyGuests:Andrew Kiguel, Tokens.com CEOCheck Out Other Benzinga Podcasts Here:Check Out All Benzinga Crypto News HereGet Moon or Bust Crypto Merch Here Join the Telegram: https://t.me/moonorbustBZ for 25% of Moon or Bust Podcast swag.Claim 1000 ZING airdrop: https://www.benzinga.com/zing Meet The Hosts:Brian MoirSolidity and React Developer | Blockchain Enthusiast | Decentralized Internet Advocate | Crypto investor since 2012https://twitter.com/moirbrian Logan RossBlockchain Analyst @ Benzinga | President @ Wolverine Blockchain | Crypto investor and educator since 2016https://twitter.com/logannrossRyan McNamaraBought sub $90 ETH during the bear market | Liquidated on ByBit | Was into DeFi before it was cool | Ran ASIC mining operation in 2016 (sorry planet Earth) | $UNI Bag Holderhttps://twitter.com/ryan15mcnamaraDisclaimer: All of the information, material, and/or content contained in this program is for informational purposes only. Investing in stocks, options, and futures is risky and not suitable for all investors. Please consult your own independent financial adviser before making any investment decisions.Unedited Transcriptboom, good afternoon. Zinger, nation. Welcome aboard the moon or bus rocket. Ship your hub for all things. All coins and defy. My name is Logan Ross, and I will be your captain on today's space flight. Okay, I'm going to be co-pilot by defiant developer, Brian Moore and exit liquidity. I mean, I mean, uh, uh, uh, best trader in the world, ran back in the mirror.Number one, Dex trader. Um, awesome. So welcome guys. How you doing? Good. How's it going to captain, captain Mike Bryan? Cause I, uh, lost a 12th word of one of my seed phrases for a wallet. I can't figure out how to get it. And so, um, I got to do some defy developing. Did you really do? Huh? That's a good, good time.Yeah, not your keys. I'll always keep your private keys and your seed phrases safe. Okay. Um, okay. So we're going to talk about Cardinal today. We're going to talk about a lot of cool stuff. Uh, but before we can take off before we can blast off, I need to go over some general safety procedures. Okay. So please keep your arms.Okay. Uh, and portfolios inside the vehicle at all times. Uh, and those who are willing and able please flip your light button into the on position. Uh, it does a lot for the show. If you're new around here, make sure to subscribe to the Benzinga channel and check out the description while you're down there.The top link is the Benzinger crypto separate YouTube channel, where you can get all of the specific crypto clips. Uh, and then there's also, let's see, we got the telegram down there. We got the merchant link down there, pick up your sick eith hat. Uh, and we got a 25% off discount code coming at you. If you join the telegram, which is also linked down below, we also have a lunar bus game, uh, which was really cool.Um, Ryan and I helped, uh, helped to build this and you can click Mooner bus. You can vote on all your favorite tokens. We're trying to get the community involved here. So check that out as well. Uh, go make your votes, check out the website. And there's also all of our old videos there. We've talked to Tim Draper, we've talked a bit, boy, we talked to the creators of ACCE infinity.So go check that stuff out. You really don't want to miss it. There's a lot of valuable info there as always make sure to connect with us on Twitter. You can see our handles, uh, hit us up. If you've got some questions you want to know our thoughts. Um, and also we want to know your thoughts. So what projects are you looking at this week?Drop them in the comments below, um, projects, tickers, whatever you got forests. We want to see it, and we'll try to talk about them. If we get some time today. Uh, we also have a sweet interview coming up with tokens.com. Uh, we have Andrew Kegal coming on the CEO of the company. Talk to us about how he's giving defy access defy, uh, um, uh, exposure to these institutional retail investors.It's really cool. Uh, so stay tuned for all of that, but first up on the docket, uh, we have car Dano, smart contracts launching, uh, kind of, kind of unexciting here. I don't want to say it's like the challenger. Uh, but, um, Ryan, why don't you just tell us what else. Cardona said September 12th for smart contracts and they deliver it.They brought us some smart contracts. They had a successful hard fork, the Alonzo hard forks, and now there are smart contracts on Cardona. So that's really cool that the youth Maxis can't say that Cardona doesn't have smart contracts anymore. So now I can't make that argument, which I guess is good, but it seems like they might only be able to process one transaction at a time.Cardinal has been having some trouble doing concurrent transactions, which is very necessary for defy. So although these smart contracts are. There aren't very many defy applications that you can use. Don Cardona. We were looking over this morning trying to find one. We could go over on the show. We couldn't find any depths on Cardona that are up and running.Now I saw that men swap one of the automated market makers on Cardona was up for a little bit, but they were having problems with their smart contracts. Like I said, they weren't able to run concurrent transactions. So they weren't able to run more than one transaction at a time on their platform. So I'm not sure if that's been fixed yet, but these applications are not up and running from what I can see.If you have any dabs on Cardona that are up and running, put them in the chair. We can have a second to go over them, look at them, see what they're all about. Uh, but as of now seems pretty lackluster. And I think car Donald's price shows that we're dipping down. I didn't check today, but I think we're, we're what low $2.Now we hit $3 last week. So I, I don't think it's looking too good for Cordato after all of this hype and now they're having problems after launch. Uh, what do you guys think? You guys are the ADA investors you're bullish on Cardona. How do you think this plays out? Brian? You want to take this one or you want me to go for it?Yeah, I can, um, say a few things. Well, one thing is a comment from the just ADA, you know, Foundation, the people who try to do the, who added the smart contracts and everything like that. They said that this is just now it's just getting started. And so there's a lot of room to run here and I don't think they want to put out a subpar, um, product or anything.But one, one thing that gives me pause is that why, why didn't they have this already ready to go for the date that they establish in? Why was it a little bit more feature rich than it actually is? That's it's not really concerning, but kind of annoying because it's like, come on, let's let's get this party started.Let's go for it. You have so much money. There's all these people invested in it. There's all these eyes looking on it. There's all this help. There's the, one of the co-founders of Ethereum's heading it off. So like what's the holdup. That's my quick. Yeah, for sure. And we saw them deploy smart contracts on their Testnet.Uh, like a couple of weeks ago we saw the same issues going on. Uh, and it's really amazing to me that they didn't fix it or delay the launch. Um, in, you know, CarNow has dropped 11% today, 14, almost 15% on the seven day. It's down to 2 42 right now. Uh, so people were saying Karmanos smart contracts. Weren't priced in.I don't know about that. It kind of looks like they were, and their, their, um, flawed execution has kind of taken a share out of their market cap, which I mean, makes sense to me. Why are they worth $78 billion? When Salada is worth $46 billion, they have this. Uh, defy ecosystem. So Ilana has $11 billion in, in TVL like locked in protocols.Uh, whereas Guardado has nothing. They have, they have a large amount of their, um, of the ADA staked, uh, for validating the network. But that shouldn't come as a surprise because what else can you do with Cardona at this point? There's no other way to make money on it. Like, there's all these different applications on Ethereum, it's Atlanta, uh, where you can get higher returns than, than just securing the network.Um, yeah, I mean, it's kind of disappointing to see this happen. I I'd like to see, uh, you know, them kind of fill out the potential to fill out, uh, the, the reasoning that they're justified with, why their market cap is almost $80 billion. Um, I think they have a, uh, there, you can tell that these guys are developers.You can tell that they are on the, you know, the technical side and know how to make things happen, but are not good at marketing. They're not good at, you know, letting people know exactly what's going on. I kind of disagree. I kind of disagree because if they're the good, if they're good at the technicals, then why aren't their smart contracts working?Why isn't the ecosystem there that their main strength I think is marketing and Charles Hoskinson is leading the way. Right? All the, all these people, all these Cardona lovers like love the project because smart contracts and Charles Hoskinson right. That's not, they have no other like justification. Um, and.I don't know, I'd like to see more happen. Well, what I think what, what I was gonna say was this looks like it was just the date. The hard fork was going to be launched. It wasn't the date that, you know, all the smart contracts everything's going to be working correctly. Everything's going to be this crazy new Ethereum, all this other stuff.It was just the date that they were going to do the hard fork and start the process. And I don't think that they made that, you know, known to all their holders to, you know, anybody, they just kind of, you know, everyone expected to go this full route in this full, like, you know, smart contracts, transactions, all this stuff.And to be just like Ethereum or salon or any, any of the others, but it looks like it was just, they did the hard fork and they, you know, now we start. You know, that's just my thought on it. It was definitely an interesting decision by car dyno, not to delay the smart contracts. Oh yeah. They knew it wasn't working.It was on the Testnet. So, I mean, they had to expect that these stamps weren't going to work when they, when they issued this hard for it. So why not delay? I mean, they get a lot of flack, especially on social media about over promising and under-delivering, I think this is one of those cases, but I think they probably should have delayed the hard fork because then the dabs could come out when smart contracts are running on the ecosystem.And it seems to me that would be a lot smoother way to do it, then release these smart contracts that nobody can really use right now. Yeah. Yeah, for sure. Um, so yeah, we've got a couple, uh, comments, one from HD 5,000 explaining about the transaction model. Oh, whoa. Can you hear me? Okay. Uh, so the, the unspent transaction model is what card auto has implemented.It it's the reason that these defy apps are having these problems. It's supposedly intentional, supposedly supposed to be bringing benefits. Uh, but we only need to see, uh, some, some sort of alternative to enable these applications, you know? Um, let's see, what else do we have here? So is it a problem with the developers that are building these decentralized applications then?And not technically Cartano smart contracts? I don't think it's a problem with the. They would like the developers building like incorrectly. I think it's just the model that Cardinal has chosen. Uh, isn't capable of handling this. It's the, it's a different model from Ethereum and it's, uh, unable to like dApps.Aren't able to do multiple interactions with them within one block is basically the, just a bit, I'm not super technical. I'm not an expert specifically on the, these deep, uh, portions of, I, um, if you guys know out there, please do drop some comments, let us know. So we can, you know, get all of our facts straight here, but, um, we'll have to see what they do in the future because without the, the, the defy ecosystem mirroring Ethereum, hearing Solana, it's going to be interesting to see what use cases they're able to pick up instead.So, um, that's what I have for today on Cardinal. Well, we can look at the prices or we can move on to, to the arbitrary news. Uh, were you guys feeling. Either way. Yeah. Maybe pull up the prices anyways. We can keep them on screen so we can maybe go over some layer twos and their prices. And then we can go over and look at how light coin has been affected by this recent Walmart news.Sounds good. I will say one thing about the last thing I'll say about the ADA thing. Cause someone just mentioned, uh, ADA tokenized or.io and I am on that site and, uh, it is in beta, but we're not saying that the Cardona does not have smart contracts. They do have smart contracts. They're just not what we would expect from the co-creator of Ethereum, but you know, it's just not ready yet.And it wasn't known how far it would go. So it's, it's still in a process and eventually it will be what we all want it to be in my opinion. I mean, hopefully we'll see some decentralized exchanges popping up soon. I know a lot of people are bullish on Sunday, swap, like to see that launch and I'd like to use it.I'd like to get my hands on it and start being active in the, in the ecosystem. And there's definitely a lot of opportunities within Cardona's ecosystem. Hopefully there's going to be some airdrops coming out. So if you're an early adapter to any of these different programs, Ancar Dano, there is a possibility that you could get airdrops some tokens, which would be really cool.Everybody loves free money. Just don't tell the S DC about it. Uh, yeah. So here, oh, this is Bitcoin. I was a Cardona for a second day. I don't know what happened. Eight years up at the Logan. Do you see one maybe for Coinbase by now finance? This will do. Um, so these are the weekly candles right here. So I was ripping through July.Uh, and now it's a correction. I mean, I don't necessarily think that this is like entirely the fault of the smart contracts. Not, I think it's pretty high. Yeah. There could be a lot of profit taking mixed in here. Uh, don't want to, to create any untrue FID, um, but we'll keep our eyes peeled on this situation and we'll keep you all updated.And we also want to know, uh, what you guys think about it. Um, and maybe you could even come on and chat with us, hit us up on Twitter. If that sounds like you. Um, okay, so let's talk about light coin next. Yes. Over the light coin. And then we can talk about arbitrary Monday or Tuesday after. Okay. Cool. We did just handles or.For show for show. Nice. Um, so you guys have been living under a rock for the past six hours. Light coin is not being accepted by Walmart. So it was fake news. It got picked up by a lot of different publications. Lots of stuff came out, but then the CEO of Walmart went on to CNBC to clear up the news. It's not actually happening.It's fake news. And the most concerning part about this, at least in my opinion, is that light coin, the light coin foundation actually tweeted about this partnership this morning saying that Walmart will be accepting them as a payment option. And then later deleted that tweet. So I don't know who sent that tweet out, who was able to do that, but it was completely fake news and it was pumped by the light coin foundation themselves.So I mean, people are talking about this being a facilitator for some more regulation coming in the space. I mean, not man. I see that because what we were at less than a hundred. $80. This news pump the price up to $236. And then once people found out it was fake news, we're right back down to under $180.So if you're able to catch that move, pick up on the fake news shortly coin, and you probably made some good money, but you got to stay up to date with this news. What do you guys think? Do you think this might cause some more regulation in the future? I mean, it's really the news publications fault for not verifying any of this information, but at the same time, light Quinn really shouldn't have tweeted about it.I mean, they're obviously wrong for that pumping fake news for their own coin. Not a good look whatsoever, I think. And there's probably a lot more backstory to this that we probably won't know because it seems like such a big deal. And if light coin foundation is bumping it. I mean, it is like announcing it, then there's something else going on or, yeah, it got the Twitter account got hacked, but that Newswire is from kind of a reputable source.And so they immediately, well, not immediately, but like a few hours an hour or so later they put a disclaimer, say, Hey, this is not true. Um, like going is not being accepted by Walmart, but it's pretty fishy. It's weird. Interesting. Weird. If you, what do you guys think if Walmart decided to accept cryptocurrencies, would they go with light coin or would they go with something else now?And, well, they're also hiring for a blockchain developer in a cryptocurrency expert, so they, they trying to create their own. So why would you accept light coin out of all of them? You know, it's just, it's just weird. All right.All right. Let us know what you guys think about this situation. Would Walmart take light coin? Would they take Bitcoin? Ethereum, Cardinal. What's going to be the move here. Um, but for now we have probably, yeah, probably doge coin. That's probably, I mean, that's from a, from a, like a technological perspective.Doge coin is the most advanced cryptocurrency in existence. Um,A whole lot of cap up in here. So I want to talk about Adam real quick. Uh, Adam has seen a new all time high today, uh, which is dope. We've talked to the creators or some of the lead developers on the cosmos blockchain on the cosmos protocol. Um, we talked to them a couple of months ago earlier this year, we talked to Dennis as well.Who's also working on the team, um, maybe like one month ago now. So go check out those interviews, uh, if you haven't seen them yet. Uh, they're really, really cool. Adam has a crazy project. That's all about blockchain interoperability, right? So there's a lot of blockchain maximalists. They say Bitcoin's the way.Themes the way to go us a lot is the way to go. Uh, and then cosmos comes over here and says, oh yeah, well, the demand for blockchain space will probably grow to fill all these blockchains. So eventually we'll need to connect them. We'll need to have room for application specific chains, uh, that can lower fees and all be connected through a hub.So cosmos blockchain is the central hub that all these other blockchains are plugged into. If you're familiar with polka dot, they got something very similar going on, but we're seeing this atom token rip. I mean, we interviewed them when the, when the coin was down here. Uh, it was such an interesting project to me that I was picking it up in these ranges.Uh, so now, now we're doing really well. This is a good day for me. Look at these. This is, these are the weekly candles here. These past three have just been nuts. Um, you guys, did you guys pick up any Adam I've been holding Adam's since it was about at $4, some I'm pretty happy with it all. Very nice. I don't have any Adam.And I mean, it looks like it might be too late, but you never know. It looks like we're in price discovery right now. And like we saw with Solano after we crossed those all time highs, we just ripped, we went up another two, 300% after that. There's really no telling where the price goes. Once we pass all time highs, especially when we're not in a bull market, per se, with Bitcoin and Ethereum at new all-time highs.I mean, typically these all Queens will follow the market, but when one of the few that don't don't and go to new all time highs, a lot of times you see really big gains. So I'm, I'm interested to see where Adam goes. I wouldn't be surprised if we saw $50, honestly. Yeah, yeah. Now they were die. Uh, so yeah, that's another one we wanted to point out today.Let's see. Should we talk about arbitrage? And we have about 10 minutes left before this interview, more like eight. I'm going to take my, my screen share off real quick. Maybe we can talk about arbitrage, uh, on a theory. Yeah, man. Our Trump's been picking up a lot of traction. There's over $1.5 billion locked within its ecosystem.It's a layer two scaling solution. It's a lot like optimism. So you, you bridge your assets onto the chain, the side chain, I guess it's not technically a side chain. It's a layer two, right? Logan. It is a layer two. Yeah. Okay. Uh, but yeah, there's $1.5 billion. Like most of this, it was interesting. I was looking to see where all this money was going within the arbitrary ecosystem.And most of it was going to this program called . So it was like a Nyan cat themed yield farming protocol on arbitrage. So since it's a layer two solution, the fees on it are much cheaper. So you can actually yield farm much more efficiently than say on Ethereum, blockchain. Uh, but this, the price of this Arvin nylon token one.50 cents 40 cents all the way up to like $8 within just a few days. And has since dumped back down to around 80 cents. So we were seeing super high volatility on this token, and it's going to be interesting to see whether these yield farmers stay in Arvind eye on with the price down so much now, but either way, $1.5 billion locked in an ecosystem that's been around.Well, I guess the ecosystem really is a theorem, but the arbitrary gateway has been around for less than a week now. And we're seeing already over a billion dollars, locked on the platform, which is just absurd to me. I mean, it took forever to see salon reach a billion dollars, and now they're at 10 billion.So we'll see where the growth goes, but it's looking really good for arbitrary. It is looking good for arbitrage and, uh, they sucked a lot of the volume out of some of the other bridges, specifically those to Solana and those. So I think Ryan, what was the other one there? And do you remember what the name of that site was?Where we could see them all. I don't remember. No. You mean Mulana, polygon and Solano, I think. And then there was one Holly gun that sounds right. But there were three and they were down like 30%, 40% and 60% well Arbitron was up. So it looks like a lot of this money coming from other layer, one scaling solutions like salon are, are actually flowing back into the Ethereum ecosystem and using these layer two solutions like arbitrary optimism, mainly arbitrary right now I haven't checked how much total value is locked on optimism, but I don't think it's at a billion dollar say actually, no, it's not at a billion dollars.USCAP because with all the layer twos outright now arbitrage has 60% of the total value locked. So compared to its competitors, it has the most by far, which is very impressive. I'm not actually quite sure. Why, why do you guys think that arbitrage is the one seeing adoption? I mean, it's pretty similar to optimism from what?Yeah. One thing is it's under the same umbrella as optimism. So it's owned by the same parent, well funded by the same parent company. So they're not technically competitors, but they do very similar things. Um, I couldn't tell you what, why one is better than the other, besides it going down to more, you know, better marketing, better selling points and just, you know, catching the right niches and places to go.But that is one interesting fact though, because they're both kind of in the same family that it's weird that they would, I mean, I really do not know. I'm guessing the arbitrary has more like volume available, more space available, uh, for processing. If I had to guess that would be the reason that it's beating out optimism at this point.Um, but they do use the same, excuse me, the same technology, the optimistic roll-ups. Um, and Ryan, I found L to beat right here, uh, and we can see there's $2.2 billion locked in arbitrary of 3000% over the past seven days. That's pretty good. I wish I could do that. Yeah. I haven't used arbitrarily yet, but Logan, I think you're right.I think it is cheaper to use arbitrary than optimism. Right now. I went in, I did a transaction on optimism on unit swap the other day, actually just yesterday. And it actually was kind of expensive. It was like 0.01 to Eve, which is probably around two to $4, which, you know, it's not bad, but compared to Solano, which is like 1 cent, it definitely doesn't really compete.It's still kind of expensive, especially if you're doing a lot of transactions. Now it's nowhere close to a theorem. That's 30, $50 a transaction, but you get that security with Ethereum. I don't think they're really competitors whatsoever. I think these layer twos are really competing with Solana and Binance smart, our chain and those other proof of stake.Smart car contract blockchains. Yeah. Killer killer question mark.All right. Uh, that is our market update for you today. We have Andrew kugel backstage right now, uh, from tokens.com. So I'm going to bring him on, uh, right now, Andrew, welcome to Muna bust. How are you doing today? I'm good. How are you guys doing great. Thank you. Uh, no on that, uh, that conversation that you guys, I mean, yeah.It's some interesting stuff around, so yeah. Yeah. What do you think about the whole, a layer two ecosystem? Are they the Ethereum killer killers? You know, I don't know. I think as a thing, I mean, if you look at what my company does, which is staking, I think that if can't move to staking quickly enough, right?So the funeral is trying to defend its market position by moving away from proof of work to proof of stake and, you know, eat 2.0 is doing that. You know, they just had that, that London upgrade. So I don't know what we'll, we'll see what happens hard to. Indeed it is. Uh, so Andrew, for those out there who haven't heard.com, uh, or heard of riot, can you, can you guys hear me?Am I cutting out? Yeah, you're fine. Okay. No, you're good. Um, so Andrew, so those who haven't heard about tokens.com, uh, could you tell us a little bit about yourself, your background coming from Chile and how you got into crypto? Uh, yeah, so I was important in Chile, but that doesn't have much to do with my crypto, but, um, I tell you the story.I was, uh, I was an investment banker in Toronto Baca in 2011 for two decades. And I got really interested in crypto back in 20 16, 20 17. And the gap that I found is you have all these people who like to invest via the public markets. So like the Robin hood type people, public market institutions and mutual funds, and they didn't really have a way of investing because the level of sophistication that you guys were just talking about.Most people don't have that. They don't have the time to do that, or the ability to do it instead. They just want an easy stock that they can by trade. It's easy to account do the taxes for and all that stuff. And so back then, um, there wasn't a lot of ways for public market people to get exposure to Bitcoin.So myself and some other guys, um, you know, probably heard of a couple of the other guys, um, Mike Novogratz created a company called headache and headache was really a Bitcoin miner. I think it was the first public Bitcoin miner. And the main thing that made it different from all the other mining companies is keep the Bitcoin that you might have as much of it as you can, you know, pay the electricity, do not keep the Bitcoin.And today, uh, headache has a one and a half billion dollar market cap. And I think outside of like, um, micro strategy, maybe Tesla owns and holds more Bitcoin than any other public company in the world. Like a tremendous amount of that coin. The one thing though, that I started recognizing last year. And it goes back to what you guys are talking about is, you know, you try to take a step back and like, what are the big trends happening in crypto and defy an NFPS?Here's the problem. You can't process the stuff really on proof of work. Like you see the difficulties that Eve has having with it, which is why they're transitioning and Crusoe state can process a hundred thousand transactions per second. Whereas crypto mining community do about 15. That's a big difference going from one five to a hundred thousand.And so I decided to make the leap from going from a proof of work company to a proof of state company. Cause I'm like, this is where the future is going. Like nobody builds anything on proof of work anymore. Like when's the last time anybody lodged a blockchain on proof of work like credentials, Salinas, everything is staking now.So if you look to the future and again, to that thought of how do you give people in the public markets, easy exposure to this, um, We create a tokens.com. So we're a public company and we take our money and we buy tokens and we stake them. So we've got a big positions in each Binance, um, Pocono and Oasis.And we're also doing some, uh, liquidity, uh, farming, yield farming stuff with the Axion infinity, uh, shards, which you get the access, which you guys are probably familiar with. And I think we may be the only public company in the world that owns that and gives it to investors exposure to that. And so that's what we're trying to do.Like it's easy to get exposure to Bitcoin. I always find it amazing in Canada. They launched a Bitcoin ETF earlier this year, and Bitcoin's probably the easiest thing for someone to buy yet. The ETF attracted a billion dollars in 24 hours. You know, all of these funds that are out there, the money keeps pouring in, which just leads me to believe that my thesis, which is.People prefer to have something public that they can buy through Robin hood or their online trader through their broker and have it sit with the rest of them as opposed to going and doing some of the work to figure it out themselves. There you go. So you are basically the micro strategy of defy, uh, giving all these.So would you say your main audience is retail then? Or would it be, would it be institutional? You know what? It's both. Um, the largest tech mutual fund in Canada called CA signature. They manage billions of dollars. They came to us and said, we really like polka dot, but as a fun, the way we're structured, we're can't we don't have the capability to go out and buy, put it.This is before dot was trading on Coinbase and it's hard for people to get, but for them, it's also like, we don't know how to get it. We don't know how to secure it. You guys are liquid, you're staking it. You're making a yield off it. And we can have liquidity through you. And so they might ask their compliance department, they said, how much of this company can they buy?They want to buy as much of this as they could, but, but you're right. That's a good example. We are like the micro strategy of defy. The big difference is I don't think Michael Saylor is making any money off his Bitcoin that he sits on. We are actually so far this year, just on our staking. We're up about a, I think it's close to 25% on our cost basis on just staking rewards.Now it's not the 3000% that you guys were showing before, but we're a little more conservative in our assets. Look, crypto's volatile, but our assets are up over 70% since the end of Q2. So just for July, August and into September, we're up 70%. So the assets that we use to create revenue are up by 70% and then those assets have created another 24% of new tokens for us.So I think it's a pretty good business model. You know, we're looking to grow it and definitely there's interest. I always tell people, if you want to get exposure to Bitcoin, there's funds, there's crypto miners. If you want to exchanges that are out there, but if you want to get public market exposure to all points and specifically defy tokens, um, there's not a lot of choices for you.If you're more like a newbie or you just don't want to go do the work yourself. That's awesome. Let's see, you mentioned that you stake to get extra cryptocurrency in your portfolio, which is obviously a great idea, but do you guys use any other defy applications outside of actually validating that works turn any passive income on your holdings?Yeah, so we own a bunch of, uh, uh, Bitcoin, um, not, not a huge position, but like a relatively decent position. So we go on like pancake swap and some of those places, and I think we're. At last check, we were running about 14% on it. So that would be more of our active strategy. But generally speaking, our core strategy is buy stake and hold.And, um, like I said, not a ton of stuff. Like we really like polka dot. I think we miss Solana Solanas are a really good one. You know, all these guys are trying to see you who can replace, you know, Ethan and there's a lot of good contenders that there are. So you guys saw, you were talking about the credential smart contract watch and, um, you know, there's, there's a ton of cool things going on out there.Um, I don't think anybody knows where things will ultimately resolve, but I can guarantee in 12 months we'll be having some very interesting conversations. I think you're right. Totally. And I see that you guys are also invested into NFT gaming as part of your portfolio. So I saw you guys are, are invested in ACCE infinity and smooth, smooth love potion, which is another token on AXI infinity.Are you guys involved with the scholarship program at all and XC infinity, like, do you actually take these assets and rent them out to players? Or how do you make the yield on your NFT gaming platform plates? Yeah, so I think right now what we're doing, it's just, we're part of the liquidity pools. Um, so we're sort of trimming it.Uh, that's what we're doing. So the returns on the S on the smooth love potion, the returns have been exceptional, the yield side, but the performance has not been awesome in the last couple of months. Uh, kind of the reverse on the AXS we're seeing amazing appreciation. I think since we bought it, it's up about 65% or something, but the, the yield on it in terms of the liquidity pools, there's only one.20 to 23% are still really great. You know, it's funny in this world and having been a bank for a long time, if you were to make like eight to 10% in a year, you'd be like real happy. You'd be like, I just had a great year. I think crypto makes you a little bit nutty in that, you know, you go through like may and June where everything drops by 60, 70% and you got really upset.And then all of a sudden everything's up and you're, you know, you're always aiming for these big returns, but, but these are good products. And if you look at the big trend of NFTs and defy what's happening, I think, um, it's not just short-term gains. I think there's like real legitimate value here to what's being created in.Yeah, I mean, making 25% interest, uh, 25% of your return on, on interest alone, uh, must have the traditional financial system quaking in their boots. Um, but I'm curious, what got you into ACCE infinity? Was it the, you know, the big picture NFT, uh, play long-term or was it the staking rewards? Um, what about ACCE specifically?Got you into it? Yeah, I think, um, it's a good question. We were looking for ways to play the NFT space and what we will never do at tokens at least for now is we'll never going to just buy an NFT parking on our balance sheet and sort of hope that it goes up. Um, we're always looking for assets that we can buy, but a, we look at the trends, like what are the, what are the high level trends happening in crypto?And then we look at what are the assets that we can buy that will appreciate as a result of those trends. And then the number three criteria is can we use technology to earn revenue. And those are really the three things we're looking for. It has to meet that criteria. So when we looked at what was happening with the Axiom affinity and the excess and that mark Cuban behind it, we just thought that was interesting.We decided to dip our toe in and get some exposure. We're looking at other cool things. Uh, I'm sure you guys have talked about, but we're looking at, uh, the metaverse maybe picking up some real estate in the metaverse. I think that's going to be the way people are talking about NFTs this year. I think in 12 to 24 months, people are going to be talking about the metaverse in the same way.Hmm. Interesting. So you're looking at decentral land. Are there any particular metaverselike, like decentral land is the one that I'm following the most closely, but we're looking at a few of them. The one I'm most familiar with to central land. I think it's super cool that during a COVID they held a music festival. Um, so like you go in there with your avatar and, you know, you buy your ticket and you go into a field and you can listen to like, you know, a pretty cool DJ spinning, spinning.Um, I just think that the whole idea is pretty wild, but you have, you know, if I'd walk into I'm in Toronto, but if I walk through my city COVID and Amazon have killed the traditional real estate model where, you know, I see all these for lease signs everywhere I walk empty stores. And when I think about the potential here for the metaverse, which is you have a collection of people who are like-minded with their avatars and you're walking around and you have money to spend, um, and the land size is limited, right?I mean, the central land is what the size of like Washington city or something. It's like, it's limited similar to Bitcoin. There's going to be a scarcity value there. And so owning this land and being able to develop it and create an amazing experience for the users and the people that are walking by. I find a really interesting cross section between real real estate, which is kind of faced.And kind of where the future of real estate is, which is going to be these, these worlds, where we have all these people with money and looking to spend it. So, Andrew, if you were to get any. Oh, Logan. You mind if I have a follow-up question to this? Uh, we're lagging a little bit. Uh, I'm sorry if I cut you off sometimes Logan.Um, but Andrew, so if you guys do end up picking up, uh, digital, real estate, stay in decentral and, or the sandbox or whatever, do you guys plan on developing the land and trying to monetize it like you do with your other investments? Or would this be more of a speculative investment for you guys? No, we would want to monetize it.We same, same thing, buy stuff that we can generate revenue from. So, you know, I know, I think it's in decentral and galaxy digital. Um, there's areas you can walk by and they've partnered with, I think it was candy, but you can walk by and see like a billboard for galaxy digital. Um, there's a lot of value there and that you have what, three and a half million people using the, and right now you can walk by, you can use it as a digital space.The zoning rules are pretty light. So can I create some kind of gaming, maybe a casino, if you do it again, there's different things you can do to create a user experience there where they they'll want to spend money. But ultimate dream is to create a, a real estate investment trust, like a REIT that pays out a dividend to shareholders, but it's entirely based on digital real estate.Hm, I think we lost Ryan. Um, but I love the idea of creating a, uh, a metaverse read. I think that has a huge potential. I know, um, I've said this before on the show, but I've, I've heard someone like Gary V mentioning that there could be more jobs in the metaverse than in the real world, uh, looking long-term.And that just blew my mind. Um, especially with the, with the advent of things like basic attention token, when users are being, uh, finally might be able to be paid for their data paid for their time, online, feeding these huge algorithms. Um, it's going to be crazy to see where the metaverse goes and how much potential value could be unlocked, um, within it.So I want to toss it to Brian now, uh, for this question, I just highlighted them. So, uh, what made you decide to move from, I heard you were doing a lot of mining and Bitcoin mining and everything like that for mining to doing the tokens.com aspect. Yeah. Two main things that I really hated. So when I was, I was a CEO of a headache, uh, which as I said, it's a great company.They're one of the largest miners in north America, one of the largest public miners. And what I really hated is, uh, every quarter you have to depreciate the hardware. And so you guys obviously know what would be a minor. You got to order your stuff primarily out of China. And it's got a better four year lifespan.And that's because as the hash rate keeps moving up, you can only produce so much if it becomes obsolete. Um, so I, it was always having this big depreciation where at the end of the four years, you're your hardware isn't really worth anything. The other thing I hated was I would have at least one call a week from the media or environmentalist.And they would tell me that Bitcoin was cool, but I was destroying the planet. And so it was kind of a combination of those things that I started looking around and saying, what else is out there? And I came across staking and I think staking was really created to improve upon proof of work. It was created as like, what are the flaws with crypto mining.And how do you improve them? And staking uses 99.9% less electricity because it's based on ownership, not a massive processing power. So that's a win. And the second one is you can't do BFI really on mining because it's too slow and that's the problem Ethan's having. And that's why they're migrating the staking.Um, so when you look at sort of like where the puck is going or where the future is that nobody builds anything on crypto mining proof of work technology anymore. It was like, okay, I've built this company. It's doing well, it's positioned to succeed, but I want to build something new here. Whereas I think things are going next.I got you. That makes sense. Yeah. I definitely agree with that with, um, what do you think about, so the Binance smart chain and E uh, Ethereum going, if you're going to prove a stake and all that other stuff, where do you think all that's going to turn in the next five years? What do you see foresee for the future of everything we've just already talked about.Yeah. So again, my purely my opinion, I think, outside of Bitcoin, um, in three years, you'll see, look at the top a hundred blockchains and there'll be like out of the top hundred, like 95, and then we'll be all proof of stake. I think, you know, crypto mining is, is, is going to be the way in the past. I think you're going to see a, a split when we started seeing that a little bit this week, but I think Bitcoin Bitcoin is not a defined crypto.We all, we, we know that and understand that. I mean, there's lightning network. Maybe that could go in and change that. I know that's what they're trying to do over at square Jack Dorsey, but generally speaking, it's probably just going to be like the digital goal. Then it's going to start spending on its own over the last few years, everything sort of hits the same.Like everything sort of hit all time highs like early may, then everything dropped at the same time. I think what you're going to see happen is there's going to be a split bifurcation between Bitcoin. As a, the G crypto that doesn't do a lot of in store value and it's still great and awesome. But then all of these other things that actually have applications and don't use electricity.Um, eventually I, you know, I don't think it will happen in the next 24 months, but I do think it'll happen. And within 48 months, I do think equal flip that coin. I agreed. I told Logan before I've told Brian, I think there's probably like a third chance that it flips this market cycle, but of course that's just to be a speculation, but the use cases are definitely there for it.Yeah. I mean, what is it? 80% of all defy products are in there are still being built on Eve. Despite there being a lot of other good alternatives that people continue to use, you know, Eve and, you know, you can solve the same thing. Remember all those Bitcoin forks, there was Bitcoin light Bitcoin cash, but critical the coin SB, those all were supposed to be improvements on Bitcoin because they would process faster.The blocks contain more data. There's a whole bunch of stuff. They never took off. And so you might have a similar thing here that as Eve evolves to staking and eat 2.0 that Abel just become more dominant. That's a good point. But even with ease 2.0, transaction fees may be higher than some of these competitors say, like Solano and Binance smart chain.Of course you're paying that price for the added security and the robust network of Ethereum. But how do you see this playing out with retail investors? Do you think that they'll actually care about decentralization and want to use a network because it is the most secure, or do you think that other projects like salon and Binance smart chain will gain these retail investors who might be priced out of Ethereum?Uh, I do think that they're going to gain traction. Um, ultimately like when somebody goes to Ave or, or pancake, whoever, I don't know that they actually care who's behind it. I think they're looking at, you know, fees and how they can maximize their, you know, their borrowing lending or trading or whatever it is they're doing.And, and ultimately. People act in their best economic interests. So as long as it continues to do it does, if it becomes too uneconomical relative to its competitors, we'll lose market share. Um, and I think that's inevitable. So we'll see what happens. It's really hard to predict, like you're saying that this is a real pivotal time, I think in crypto, because you do have all these things that are up and coming this Atlanta as a crutch, nanos, um, all these different things are challenging Eve.And we'll see in the next six to 12 months, if there actually is adoption into those, um, the way people are expecting and pricing into the tokens. Hmm. So, um, when do you see ETH 2.0, launching? And do you think it's going to affect the proof of stake and everything that we have? Like, do you think it's going to affect all the chains?You mean? Yeah. Sorry, can you repeat that? We'll never be able to successfully upgrade or launch. So E E 2.0, has already launched and we're staking it right now. We own about, uh, over 2,500 east 2.0 that we're staking and earning. And the, if you, I mean, there's lots of sites you can look that you can look at, but the adoption is, is moving pretty quickly.I think at the last estimate, I saw that it was probably about another 24 months before the it's kind of a slow progression. It's not going to be, it's not an overnight flip into staking. I think it's, uh, uh, flipping into the evening. The other thing is when you're staking Eve, there's a, like a locked period or a bonding period, which I think this is really interesting and will help appreciate the value within here's why mining, which is predominantly how Ethas is secured right now, how the blocks are valid.You have to still sell your Eve as a miner to pay for your electricity and your hardware, right? If you use a staking company or is it staking a token, the money stays within the ecosystem. As a Staker. I never have to sell my Eve to pay for stuff in the outside world. I can keep it in there and continue accumulating and compounding it.And I think that's really smart decision because if you look at what's happening in Bitcoin during the crash, all the miners, the Bitcoin miners were like mining had to meet their costs. They were taking all their selling their Bitcoin as quickly as they could to pay for their costs in staking, the money stays within crypto because you know what, it was a really bad idea that you have to sell your crypto in order to pay for validating it.This allows it to all stay within the ecosystem, which means less selling pressure. Hopefully. What do you think that means? ETH. What do you think that means for all the ETH quote unquote killers out there that are trying to be a better version of, you know, a POS at theory them? Yeah. I always say P POS tricky, tricky, uh, acronym, but yeah.Um, I think they all function the same, so they all have different whole periods. So for example, dot is 28 days. Eve is a lot longer, but generally speaking that they're all different, but similar. And so they all keep as, as a staking tokens, they all keep their tokens within their own ecosystem. Um, so I don't know that that, that the staking aspect is really going to be what makes the decisions.I think it's just going to be the usability, but my perspective is Eve can't move to eat 2.0 quickly enough. Um, because you know, at the very least, you know, right now, Crypto mining as a bottleneck for Eve it's like drinking water through a pinhole. Like it's, it's hard. It slows it down and you get the fees.Will that change people sort of debate back and forth. But nonetheless, I think it's Eve is going to survive. It has to migrate to stay can quickly. Yeah. And for sure, we'll see, we'll see optimism arbitrary and all these layer twos, uh, kind of help along the way until we can get that, uh, the full sharding and the beacon docking.Um, so I have a question for you about regulation. How do you think the next few months are going to play out in Canada or, or in the United States? Um, for the crypto markets and, um, could this affect price action? Yeah, it always seems when there's a rumor out there or the sec comes out with something that there is a lot of, um, movement on that, you know, it's a bit of a loaded question.Like I think the key thing right now, everyone's looking at as this Coinbase sec battle, right. And I always say follow the money. And if you look at, you know, who sort of backs and influences the sec, it's the bank. And so I don't think it's a coincidence that they're like, you're not allowed to lend money.People are not allowed to make money. What was a 2.8% that they're offering it? Wasn't like, it wasn't anything crazy. It wasn't something crazy. But if you were a bank, this has got to be pretty intimidating. Right. And I know even from our company, you know, sending a wire, if you've ever had to send a wire through a bank, you have to get it there by like three o'clock.If you don't get it there by three, it's got away the next day and the money disappears for like 24 hours. And then you got to check the Atlanta, not lad. It's a really silly system and they'll charge you like 50 to a hundred bucks per transaction. It's still pretty amazing that with, you know, I know eat the fees can be high, but even with Bitcoin that I can send any amount of Bitcoin almost anywhere in the world, 24 hours a day.Anytime I want, I can do it within 10 to 20 minutes and it'll cost me like a dollar 50, if I pay for, you know, to prioritize it, right. Like. The banking system. This is why defy in my mind is just going to be the it's a massive game changer and wall street. It is embracing it. And Silicon valley is embracing it.It's just like the traditional banks that are, I think they're really scared because they can see their business model no longer works. Right. It's like being a taxi driver and trying to fight Uber. Eventually you will lose. Yeah. ACH is a definitely a outdated system and just needs to go away, just cash checking and all that.So hopefully that. And have you ever tried to send money abroad? I remember I'm from Chile that you guys pointed out. So sometimes I I'll send, I want to send some Viet to like my cousins or something as a gift. Like, you'd go, you've gotta fill out pieces of paper, the switch system, and like, what's that bank's code.And then it's got to go through a bunch of other banks by the time it gets there, you've lost 10% of your money given all the different fees. And it takes four to six days, right? Like. It's like a, it's like using a buggy and horse, you know, to get around, right. Like it's an old system. And then today, like the technology is here.I should be able to send money to anybody in the world that I want within 15 minutes and not have to pay more than $5 and lose 10% of what I'm sending. Boom, exactly. I mean, it makes sense today and looking back it's like you said, the horse and buggy is a perfect analogy there. Uh there's really no. Or, and Trish finance certainly should be scared.Yeah. Yeah. And, and, and, and proof of work token should be scared too. All the stuff like, I mean, the majority of the proof of work tokens are there, but all these, like the coin forks, like, are, are they going to become a less relevant? I know they use them for some testing, but no one's programming anything on, you know, some of these things that I am aware of it, cause it would be kind of like creating apps where a flip phone, right.It's like, it's a. Only doge coin right now, but you know, that's part of it, but you're right. You know, all those were created before the proof of stake model came out. So yeah. Uh, Andrew, do you think that we could ever see a proof of stake? Bitcoin? Do you think that that, that network has the ability to make an upgrade of that size?So I am not the most technical guy. I'll give you my opinion. I put this down on Twitter wines and men like Bitcoin maximalists are so fanatical. They go crazy. Like literally started getting so much hate messages. I do think at some point in four to five years, when the, the energy use and Bitcoin, the hash rate goes up, I think there could be potential consideration and people may hate this.Maybe there's some kind of a hard fork or something into something that uses less electricity. You're staking similar to what. Um, but I think there's going to be, again, I don't understand that the technicalities behind it, but I'm pretty sure if like the entire Bitcoin ecosystem got together and said, let's form this into something with the same value, but that it has more processing power and uses less energy.There might be support there isn't today. Um, I think it's like sacrilege and people listening to me would be like, that'll never happen. But I just think that that the hash rate is going to continue to go up. And at some point there'll be more and more prevalent. You know, you got some real fanatical people on the other side of the United States, like Elizabeth Warren who are wanting to shut crypto down.And so at some point, you know, Bitcoin has an optics problem. It's kind of like a reputation problem. I think they need to figure out something to do as a community beyond just like the Bitcoin council that Michael Saylor started to talk to you on Musk. If the technology is there to use less electricity than they think that the Bitcoin developers and people behind the chip should explore that.Yeah, well, Bitcoin is certainly not new to having these, uh, uh, you know, public appearance problems. They've been called us all sorts of things since inception. Uh, so hopefully we'll be able to see public embracement long-term uh, I think, uh, as you know, Ryan and my generation continued to grow up in, you know, Weldon become a bigger part of the market than my frozen.Now you're now you're just rude. Well, our brains are boomer. Geez. Uh, I think our generation is more crypto native, and I think that we'll see this play out pretty well longterm. Uh, and, and I think that you agree, um, by Andrew, thank you so much for coming on and chatting with us today. Uh, it was insightful and we'd love to have you back on in the future before we wrap up, I just want to open the floor up to you to give any shout outs or leave the audience with any final thoughts you have.Yeah, I would just say if you want that check out tokens.com. Um, we've got some good information on there. I think someone was looking to get exposure to crypto, but didn't want to go through the process of setting stuff up. I think we're a really great alternative for people to consider. We started trading in the U S today under OTC.Um, and so now we are training in Europe, Canada, and the us. So, um, yeah. Look us up, link in the description below. Go check it out, guys. Andrew, thank you so much for joining us today. Uh, thanks. Alrighty. Uh, Mahesh, let me grab that link for you. It is in the description below it's tokens.com, pretty simple. Um, yeah.So what did you guys think, uh, of the interview today? What'd you guys think of tokens.com? I think there's definitely, I mean, there's clearly, there's clearly a need for it. There's clearly a demand for it. Lots of people don't want to go through the hassle hassle of custody and their own crypto, uh, and you know, trying to figure out how to earn interest on all these different platforms, how to stake on these different networks.How many wallets do you have to keep track of? Um, I, I think it's a good product and clearly it's been very successful. I like it better than. Um, and they have the huge markup. I don't like that. You think that millennials aren't ready for crypto and it's only gen Z, but we can talk about that later. Uh, go back to eating your Abacus benefits or money on avocado toast.How are they supposed to buy Bitcoin? And you guys weren't even born when Bitcoin was around. Yeah, you're right. That's a good one. Now you got me there. I wasn't born until last week, so geez. I'm pretty new to this whole thing. G jeez, Ryan. All right. You want to do well a Mooner bus today. We have about 60 seconds left.Uh, I saw someone talking about VJ in earlier and maybe we could talk about that. We tasers and we, we, we talked about V train a couple of times, but I don't think we've talked about taser at all. Maybe we should talk about tasers. They've been popping off lately. A lot of these, uh, different, these other projects that like kind of got left behind from Ethereum blowing up and buying it, smart chain, blown up and everything like that.There's some pretty cool things that are going to happen. And I think a lot of people believe that, you know, it's only going to be Bitcoin. It's only gonna be a theory. Um, but there's so much, there's a lot of people in the world. There's a lot of time, there's a lot of people into different things. So I think there's room more than enough room for everybody to get a piece of.Guys my, my, uh, birth certificate exists on chain only. I am an on chain asset in case we were wondering I was minted, not born. Uh, okay. So here we go. Here stays as a yellow, too funny. Um, here's tasers, let's pull up the seven day. The one month is certainly on a tear. Let's see how it's been doing since the beginning of the year.Ooh. It looks like we're in price discovery mode. This might be a good time to pick some up. Um, tasteless is another smart contract blockchain. Um, it's not talked about a whole lot, but it is in the top 30, a market cap of $6.6 billion. Um, do you guys hold any tasers? What do you think about it? I, I don't hold any, but I do like it, um, in the sense that I, I, like I just said, I think there's room for a lot of these others to grow and to get to the potential, you know, really big returns down like.I don't hold any taser though. So it's definitely an interesting project. And at $6.6 billion market cap, you could see a 10 X by the end of the market cycle, in my opinion, that would bring it to $66 billion market cap, very expensive, but still quite a bit less than Cardona. And I do think Tesaro's has smart contracts on it.If I'm not mistaken, I believe they do. Um, and yeah, so it looks like they're, they're one of their defining features is the ability to upgrade without a hard fork. Um, I don't know if this is necessarily a good thing. I've heard metallic make the argument that that hard forks are actually more inclusive, um, because you're not forced to adopt the upgrade.Like you are in a soft. Uh, you can choose to take the other path, but, um, I'm sure that they have learned from all these years of blockchains and forks and they're doing something pretty cool. I'm going to have to, uh, dig in while I hold a little bit of taser. So I really just picked it up because I heard people talking about it.Um, but this was like a long time ago. I really haven't been active in the ecosystem since then, but it's up 18% today, so that's pretty cool. Um, I'm gonna give this one a moon. What do you guys think? Yeah, I mean, it's, it's, it's one of those quote unquote old school and I used that in crypto, in crypto, uh, years, but it, it, yeah, I like it.It has a lot of room. It's just like up there with the other ones we were talking about today. There's definitely potential and there's no reason why it would fail. I think it would. I'll give it its third moon too. I mean, obviously this asset sector is hot right now. Proof of stakes, smart contract blockchain.That's where all the hype is right now. We've seen it with Cardona. We've seen it with all the other blockchains out there, polka dots, Ilana. So I wouldn't be surprised if we see a much higher present tasers. So yes, I give it a moon. Awesome. And you guys can pick this up on coin. It's a crack in, I think we got some links in the description down below.If you want a little sign up bonus, if you're making a new account, go check those out. Um, but I'll stop with the promos. Silly me. Um, okay, so killing me, loading Ross. So this whole thing is just a sponsored, sponsored advertisements. Uh, okay. That's enough. Um, speaking of, well, we have replacement. Follow me on Twitter.Check it out. That's all I got. Check us all out on Twitter. We'll give you some dope. Uh, and speaking of checking other things out, state tune to Benzing as YouTube channel, we got more great content coming up for you today. We got pre-market prep at the close. Uh, I'm not sure if that's the next show. If we got trivia beforehand, but whatever it is, stay tuned.You don't want to miss it. It will redirect you automatically. So don't go anywhere. Don't touch anything. The Touche par thank you. This has been wound or bust your home for all things. All coins and defy. We will see you on Wednesday with another sick interview. We have the Salada Phantom wallet. You don't want to miss it.You guys got anything else? Any closing remarks for us? Not yet too many Twitter followers lately. Guys, I've been really sad about it, but a little depressed. Haven't been able to get out of bed every day. Really. So if you can just, um, attitude that they have the Z attitude, but yeah, I've been really sad about it guys.So cheer me up, please follow me on Twitter. Alright. On that note, we'll see you Wednesday.Support this podcast at — https://redcircle.com/moon-or-bust/donationsAdvertising Inquiries: https://redcircle.com/brandsPrivacy & Opt-Out: https://redcircl

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#ASCO21 Highlights in Immunotherapy With Dr. Jason Luke

Play Episode Listen Later Jun 23, 2021 35:35

Dr. Jason Luke, director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center, discusses advances in immunotherapy across the spectrum of malignancies featured at the 2021 ASCO Annual Meeting. Transcript: ASCO Daily News: Welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Jason Luke, the director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center. Dr. Luke also serves as associate professor of medicine at the University of Pittsburgh School of Medicine. His clinical focus is on immunotherapy for advanced solid tumors, as well as cutaneous malignancies and melanoma. He joins me to discuss advances in immunotherapy featured at the 2021 ASCO Annual Meeting. Dr. Luke has relationships with most of the pharmaceutical companies that have funded the research discussed in this episode. His full disclosures are available on the transcript of this episode. Dr. Luke, always great to have you on the podcast. Dr. Jason Luke: Well, thanks so much for the invitation today. ASCO Daily News: Well, there was an abundance of novel therapies and practice-changing studies presented during this year's [ASCO] Annual Meeting. Did you detect any themes among all of the great studies presented during the meeting? Dr. Jason Luke: Well, I agree. And as I was sort of taking the fire-hose of abstracts in this year, I thought there were four themes that really seemed to stand out to me. And when I was thinking through them, I think the first one was the validation of a new checkpoint, or a third validated checkpoint for use in clinical practice. A second one was really the emergence of immunotherapy, now being used in the curative setting, meaning either in adjuvant studies or in neoadjuvant studies. And the third area was advancements in this management of metastatic disease with practice-changing trials. And then the fourth area, which is always near and dear to me, is novel therapeutics with the development of the next generation of immunotherapies, and those early data that might give us a hint towards what might be coming next. ASCO Daily News: OK, so let's first look at the third validated checkpoint for use in clinical practice. That's Abstract 9503. Dr. Jason Luke: Yeah, absolutely. So this year at ASCO, we saw the results of a clinical trial described as the RELATIVITY-047 study, which was a global randomized double blind phase II/III study comparing anti-PD-1 antibody with nivolumab (nivo) versus a combination of nivolumab with the anti-LAG-3 antibody relatlimab. And so LAG-3 is a molecule that many will be familiar with, but perhaps not everyone. And LAG-3 is another receptor on T cells that can become up-regulated as T cells become dysfunctional in the tumor microenvironment. And so all are aware of the concept that infiltrating lymphocytes can get into tumors, and then they get blocked by these immune checkpoints. And so LAG-3 is another immune checkpoint expressed on these tumor infiltrating lymphocytes. And I don't have time to go into all of this, but in the preclinical space, blocking LAG-3 with an antibody is actually, in many mouse models, more effective than blocking a PD-1 or PD-L1. And so there's been a lot of interest. LAG-3 was one of the first targets to really develop as a co-target to PD-1. And just to zoom forward then to the clinical trial, this was a study where patients with advanced, untreated, metastatic melanoma were randomized one to one to either get relatlimab plus nivolumab, in what they are describing as a fixed dose combination, meaning that there's an infusion of the dose once a month, relatlimab 160 milligrams plus nivolumab 480 milligrams. And that was the same dose. And so it's only one infusion, even though it's two drugs, one infusion. That was compared with nivolumab. And there were a number of stratification factors, et cetera, in the study. And they're useful to get into the minutia, but right now, I think not so important. This, like I said, was a gated study, meaning they did a phase II trial first, to try to prove that there was a benefit in a smaller sample of patients. And if they hit the endpoint, they then went on to a phase III trial. And that's exactly what happened. So in this trial, progression-free survival (PFS) was the primary endpoint. And, interestingly, it was evaluated by blinded independent central radiology. And that may sound like a mouthful, but we'll come back to why that's important a little bit later. And there was a hierarchical testing strategy, such that the PFS had to be established first, before the investigators can look at overall survival and overall response rate. But given that background, there really was a quite substantial and clinically impressive difference between these two arms. And so we call relatlimab "rela" for short. So rela plus nivo demonstrated a substantial improvement, markedly statistically significant improvement, compared with nivolumab monotherapy, so that at 1 year, at 12 months, the progression-free survival for the combination arm was 47.7%, compared to 36% for nivolumab. And the median PFS was 10.1 months for the combination versus 4.6 months from nivolumab. So you can see that's more than a doubling of progression-free survival, with a hazard ratio at 0.75 and a p value at 0.006 or 0.0055. So why does that matter? Well, we have thought for a long time in the field about combination immunotherapy, and people think of PD-1 and CTLA-4 combination. And these data, when compared sort of across trial comparison, which is always a little dangerous, but they look very similar to what we saw with nivolumab plus ipilimumab (ipi), in terms of the absolute improvement in the benefit in terms of median progression-free survival, between relatlimab plus nivo, as compared with ipi plus nivo in the CheckMate-067 study. And I mentioned this blinded independent central radiology, that complicates things a little bit, because the landmark comparisons between having the radiologist evaluate the scans and having the investigators evaluate the scans, actually gives a little bit of variation in terms of the outcomes. But if you just compare them on a high level, they actually look very similar. And along those lines, the really important thing is that relatlimab plus nivolumab is much better tolerated with much less side effects than nivolumab plus ipilimumab. So, in fact, in this clinical trial, we see that the rates of grade 3-4 adverse events are on the order of what we saw with nivolumab monotherapy in CheckMate-067. Now, interestingly, in this study, RELATIVITY-047, the rates of grade 3 adverse events for nivolumab monotherapy were actually about half of what they had been seen in the previous phase III trial. And I think that that just suggests that all of us, as a field, are getting better at managing these immune therapy toxicities. One other piece of information that was very interesting to look at was when the outcomes were broken down by subgroups, particularly the biomarkers of PD-L1 positivity, and LAG-3 positivity. These biomarkers actually did not inform the outcomes, in which case, I mean, that nivolumab plus relatlimab was actually effective across all the subgroups. And so one might have hypothesized, going into this, that patients with high LAG-3 would do better with a LAG-3 treatment. That was not what was seen. In fact, all patients benefited with the combination. And that's relevant to clinical practice, because, as we think about applying this treatment, I do not think we're going to be able to use biomarkers, at least initially, to be able to differentiate who should get what. And rather this just suggests that basically all patients who are going to get PD-1 monotherapy would be better served by giving the combination. So I was the discussant actually for this abstract, and one of the questions I tried to get at was, well, does that mean that you would just essentially replace PD-1 monotherapy across the board in melanoma with this combination? And I think the answer is, not quite yet, but maybe someday. And what I mean by that, is that there are still some very high-risk patients that we treat. And particularly those are patients with high lactate dehydrogenase, brain metastases, rapid progression, et cetera. And those are the patients where, at least I, predominantly use nivolumab plus ipilimumab, or nivo plus ipi. And that's because nivo plus ipi is the treatment for which we have the best long-term data, and we know the most about it in terms of treating high risk patients. So I would continue to use that until this trial, at least. Is more mature, so that we can get data about the response rate, the overall survival, and so on and so forth. But I think there's really no question, looking at this relatlimab plus nivolumab data, that it does change the standard of care in melanoma, and that, for most patients, who would have gotten PD-1 monotherapy, they're now going to be directed towards this combination, given it's well tolerated and appears to be highly active. And I think, thinking beyond melanoma now, if this is now a second, a third checkpoint, but a second one we can combine with nivolumab with little toxicity, I think it opens up a huge new world of clinical investigation, possibly adding doublet checkpoint to chemotherapy. Basically everyone everywhere we've seen PD-1 combined with chemotherapy, and obviously that's quite exciting just thinking about improving outcomes. And we're going to discuss all the different ways that PD-1's been impacting the standard of care across different settings. ASCO Daily News: Excellent. Well, let's shift our focus now to the curative use of immunotherapy. Let's start in the adjuvant setting with the KEYNOTE-564 study. That's LBA 5. Dr. Jason Luke: So plenary presentation for the KEYNOTE-564 study, which was adjuvant pembrolizumab versus placebo in high-risk renal clear cell renal cell carcinoma. And so this is an important trial, because there have been decades, actually, of immunotherapy clinical trials in the adjuvant setting, which have not demonstrated a benefit. That also includes actually VEGF-TKIs, which also did not show a benefit. But in this large study, so almost 1,000 patients, 994 patients, they were randomized one to one to receive pembrolizumab or placebo. And the eligibility population were pathological T2 with intermediate and high risk features all the way through metastatic disease that's been fully resected. And the outcomes here, again, I think were very impressive. And so the disease-free survival was statistically significant, with a hazard ratio of 0.68. And what does that mean in reality? Well, the 2 year disease-free survival was 77.3% for the patients getting pembrolizumab compared to 68.1% for those getting the placebo. So you can see basically a 10% 2 year improvement in disease-free survival. And though the data were quite immature, the early analysis of overall survival also suggested a statistically significant benefit. So p value was 0.02 and hazard ratio was 0.54. Now we'll be very interested to see how that matures over time. But I think again these are practice-changing data, to suggest that, basically, all high-risk patients with clear cell renal cell cancer are now going to be receiving anti-PD-1 immunotherapy in the adjuvant setting. I think it does raise the question, and we'll discuss it now across other diseases as well, in terms of, are we over-treating patients. But this has been a constant struggle in medical oncology for many, many years. But it's very hard to see a treatment like this, with such a benefit, and not think that you want to give this basically to almost all the patients. But, hopefully, biomarkers to inform which patients benefit most will be coming over the relatively near future for renal cell. But I think those are becoming a little bit more obvious in some other diseases. ASCO Daily News: Looking at non--small cell lung cancer, Abstract 8500, that's the IMPOWER-10 trial, that caught a lot of attention. That was trending on Twitter for a while. What are your thoughts on that trial? Dr. Jason Luke: Yeah, absolutely, so the IMPOWER-010 or 010 study, this study looked at PD-L1 inhibition in the adjuvant setting, versus a placebo. So this was another very large trial where patients with early to later high-risk disease, so stage 1b to 3a, they received standard chemotherapy as adjuvant treatment, but then were randomly assigned to get PD-L1 versus best supportive care. And this was an interesting clinical trial, [ and] had a complicated statistical design where the first analysis was to look at the impact in PD-L1 positive patients. Secondarily, then, they looked at randomized patients. And then thirdly, they looked at intention-to-treat. And this was a positive study. So in the disease-free, in the PD-L1 high patient population, the disease-free survival did not reach the median, with a 2 year benefit at 74.6% versus 61%, so again a 13% improvement in 2 year disease-free survival. And that was highly statistically significant, hazard at 0.66. And, again, that's the PD-L1 high population. So, thinking about biomarkers then, it looks clear that the PD-L1 positive group is the one that disproportionately benefits, because as we went through the rest of the hierarchical testing, the disease-free survival in randomly assigned patients, and then in intention-to-treat patients, those numbers got a little less strong. And it really probably suggests that the PD-L1 positive group is the one that's going to drive almost all of the benefit. So it'll be interesting to see how this data matures, and how it's interpreted in the community. I mean, you mentioned the discussions on Twitter, which I sometimes participate in. And I'm going to come back to a little later how it's very interesting to see how thought leaders for various malignancies sort of take these data into consideration. I think clearly in GU cancers, when we talked about the KEYNOTE-564 pembrolizumab data, the sense was, this is an immediate change in the standard of care. When we look at this data for non--small cell lung cancer, however, the sense I've gotten from some investigators is, this is early data. And they really do want to see that overall survival before that's really going to have high uptake. But we'll have to kind of see how that goes. Maybe selecting for PD-L1 in that population would make that difference, to really let you feel confident. But it'll be interesting again, like I said, as more time passes and as we see more data, and as other PD-1, PD-L1 agents come into this same space, if there's reproducible data that will help them feel more confident. ASCO Daily News: Right, well, another trial that attracted a lot of attention was CheckMate-577. That's Abstract 4003. Do you think this trial will move the needle in esophageal or esophagogastric junction (GEJ) cancers? Dr. Jason Luke: So I think this is a real important trial, because we've historically thought of certain tumor types as immunotherapy sensitive versus not sensitive, melanoma, lung cancer, et cetera. And gastrointestinal (GI) tumors predominantly have fallen into that latter group, where we think where there isn't as much of a benefit. Obviously there are approvals for esophageal and gastric cancers, but I think this study really shows how we can move the needle in terms of maybe curing more patients. So CheckMate-577 looked at adjuvant nivolumab. And these were stage II and stage III patients with esophageal or GEJ, and they got neoadjuvant chemoradiation treatment and then surgery, all of that being standard of care, but then went on to get a randomization 2 to 1 to either nivolumab or placebo. And again, as you mentioned, this is an important trial. The disease-free survival (DFS) was statistically and substantially improved for the patients getting nivolumab versus placebo, after that definitive therapy. So in the group receiving nivolumab, the median disease-free survival was 22.4 months, compared to only 11 months in the patients getting the placebo. That was a hazard of 0.69 and a p value at 0.003. And, again, thinking about biomarkers here, there was a broad population of patients treated. But when you look at the breakdown of who benefited the most, the patients benefiting in this trial were almost entirely those patients who had a PD-L1 composite signature at greater than 5, combined positive score (CPS) greater than 5. And so it's really the case that the PD-L1 positive patients with esophageal cancer seemed to benefit the most. And so I don't know how you think this doesn't impact the standard of care. In the total population there was a doubling of DFS, and in the PD-L1 high it was actually almost a tripling. And so I think, immediately, at least for PD-L1 high patients, they should go on to get adjuvant PD-1 after definitive chemotherapy, radiotherapy (RT), then surgery. And I think this is really exciting, when we think about, this is disease, obviously, it's very, very difficult to treat. And outcomes in metastatic disease are not what we want. And this really suggests we may be able to really benefit a lot of patients moving forward. ASCO Daily News: Excellent. So what are your takeaways from Abstract 9500, the KEYNOTE-054 trial of adjuvant pembrolizumab for melanoma? Dr. Jason Luke: Yeah. Thanks, so in melanoma we've had immunotherapy with checkpoint blockade now for a decade. And adjuvant clinical trials have been ongoing for most of that decade. And it's been standard of care to give our patients checkpoint blockade again for several years. I think what was really interesting about the update for KEYNOTE-054, which was the study of pembrolizumab (pembro) versus placebo in stage III melanoma, was the authors on this update looked at the impact of crossover after initial progression. So in the clinical trial, patients were randomized one to one to either receive pembro or placebo. And at the time of progression, they could then cross over and get the other treatment, right? So this trial was the first trial to be designed to be able to ask that question, immunotherapy now versus immunotherapy later. And what we observed in this study was that the response rate to getting pembrolizumab in the metastatic setting, if you had gotten the placebo on the adjuvant trial, was approximately similar. It was right around 40% And that's actually what we saw on the KEYNOTE-006 study that got pembrolizumab registered. So that was really, really interesting. And it suggested that if patients progress in the adjuvant setting and get treatment with PD-1 in the frontline metastatic, and they're still in good shape, they actually can have similar outcomes than what we would have expected if they had not had that adjuvant experience. And so I think this is really important. It doesn't actually answer the question about overall survival, which is really what we want to know. Does adjuvant immunotherapy improve overall survival? But it does suggest that patients can have this benefit, even if they wait for treatment. One thing that was really interesting to see was that, for those patients who had pembrolizumab, in the adjuvant setting, and then had a progression event, who went on to get pembrolizumab again, actually had much lower outcomes. And so I think that that's something to be cautious about. I think if patients progress on adjuvant PD-1, the data from this trial really suggest that going back to PD-1, even if there's been a period of time, is not a real great idea. And many of us in the field have kind of advocated of going to CTLA-4 combination in those patients anyway. But I would think these data really do suggest that that's important. So broadly speaking, then, I think these data are important to suggest that if you wait to give immunotherapy, you can still get a good benefit, at least in melanoma. And what I thought was really interesting across all of these abstracts, so for kidney cancer, lung cancer, esophageal, melanoma, was we saw, I think, based on the investigator feedback, or the thought leaders in the field, was that disease-free survival or relapse-free survival was really interpreted somewhat differently in different settings. And so I think, in melanoma, I think we have for a long time thought that adjuvant therapy was important, despite the fact, we don't have overall survival for PD-1 antibodies. In the renal cell data, again, where immunotherapy has been a backbone, albeit with IL-2 and various different immunotherapies, again, a lot of enthusiasm. When we looked at lung cancer and esophageal cancer, where I think investigators are more used to biomarker selection, they were a little more nitpicky about which populations we should treat. And so I'm very interested to see how this entire field sort of develops, and how the thought leaders for each disease take these data in. But, if you take a step back, on a really high level, when we think about giving PD-1 checkpoint blockade, it's generally speaking a low-toxicity treatment. And there's a tremendous impact on recurrence and potentially cure in the adjuvant setting. And that is just so exciting when we think about truly making a difference on cancer. We're talking about people never having recurrence and never dying of metastatic disease. And if we think about the outliers among the thousands of patients that have these diseases, and just go out to 5 years, 10 years from now, that's going to be a lot of people alive because they got immunotherapy after surgery. ASCO Daily News: Well, that would be fantastic. Thanks, Dr. Luke, for your great analysis of the adjuvant setting. Let's focus now on the neoadjuvant setting. Abstract 8503, the CheckMate-816 trial, seems to be on everyone's radar. What can you tell us about it? Dr. Jason Luke: Absolutely, so I think we just got done talking about adjuvant therapy. But an alternative would be to say, is there a way that we can deliver this immunotherapy, perhaps to enhance the immunotherapy and either improve the surgery or actually maybe even avoid the surgery, moving into the future. And so that is a really exciting paradigm as well. And so the first of these was in non--small cell lung cancer, the CheckMate-816 study. And the initial results of this study were actually presented at AACR earlier this year, but now updated here at ASCO. And what we saw was that there was a major improvement, 10 times improvement, in pathologic complete response for giving nivolumab plus chemotherapy. I mean literally 2% pathologic complete response with chemotherapy, up to more than 20% with this combination with immunotherapy. And what the investigators updated here was a number of details around the surgical plans, showing that the surgeries were easier, and the patients had better time recovering, due to lower disease burden for those that got the combination with immunotherapy. And I think that's really, really exciting, because, I mean, it suggests a paradigm in the future where we can reduce the amount of surgery. So one of the things was they looked at the number of open thoracotomies versus VATS procedures. And a number of patients who got immunotherapy had a much lower surgical burden. So, I think those data are really exciting. They're not quite ready for prime time yet, because I think we need larger studies to prove this, but I think the trend is, we'll talk through these different disease settings, really does suggest that immunotherapy is going to really change all of oncology, in terms of surgical paradigms, how we follow patients, et cetera. ASCO Daily News: Excellent. Dr. Luke, you spoke earlier about the phase III study of relatlimab and nivolumab. There's another study, Abstract 9502 in the neoadjuvant setting, right? Dr. Jason Luke: Yep, and so, in addition to the phase III data for relatlimab, there was also a neoadjuvant study from The University of Texas MD Anderson Cancer Center group, which I think was really, really useful in helping us feel more confident actually about the metastatic disease data, and about understanding where the field in melanoma is going. So, in melanoma, that's where, sort of taking a step back quickly to note that there have been a whole bunch of neoadjuvant clinical trials done over the last 3 to 4 years, and actually so many that we've already started to have meta-analyses to look and see and observe, I should say, that those patients actually who have major pathologic responses, and those with complete responses, generally speaking, don't recur. And this is really exciting. It's actually even led to clinical trial designs where we're actually deferring surgery in melanoma, where we give neoadjuvant therapy. We take out one node. And if it's a complete response (CR) we don't even do the surgery. So in the Abstract 9502, again relatlimab, the anti-LAG-3 antibody was combined with nivolumab. And I think what the important thing to highlight here was that the rates of pathologic complete response and major partial response actually looked very similar to what we saw with nivo plus ipi in previous clinical trials. So if you remember, the relatlimab data in the metastatic setting was only the PFS data, due to the statistical plan. But what we see here is that in the neoadjuvant setting, very similar outcomes for relatlimab plus nivo as what would have been expected for ipi plus nivo. And I think that gives us, again, more strength and more confidence that this is a very active combo, again, with lower toxicity relative to nivo plus ipi. ASCO Daily News: OK, well, Abstracts 4503 and Abstract 4504 looked at alternative management strategies in bladder cancer. Can you tell us about these data? Dr. Jason Luke: So these were two really interesting abstracts, I thought, from my perspective. And they really looked at management, alternative management strategies for muscle invasive bladder cancer. And so the first one, 4503, was the Hoosier Oncology GU study 16-257. And this was a study that looked at neoadjuvant nivolumab plus gemcitabine and cisplatin, with an evaluation for clinical outcome. So what I mean by that was, after the patients got this treatment, they were evaluated for whether or not they had had a clinical complete response, and then they were offered the opportunity to either not pursue cystectomy, which obviously is highly morbid, or to continue to be followed. And, very interesting, the study, for those patients who were deemed to have had a complete clinical response, 70% of them did not recur. And that's really exciting, because if you think about the population of patients with bladder cancer, many of them elderly, those cystectomies are highly morbid surgeries. And this suggests that we may be able to move into a future where we could give them upfront medical therapy and actually potentially avoid that surgery. The other abstract I thought was really interesting was sort of married to that, which was the 4504 abstract. And that was a clinical trial that looked at the neoadjuvant administration of pembrolizumab plus gemcitabine chemotherapy and radiation treatment. And, again, what they observed in that study was very high rates of pathologic complete response, and longer term outcomes that looked very exciting. And I think what both of these studies show, as phase II studies, is the possibility that medical therapy might actually be curative in some patients. And there are a number of phase III efforts now ongoing to try to amplify these trials and actually confirm them on a larger scale. ASCO Daily News: Shifting our focus now to practice-changing trials in metastatic disease, GI oncologists were very pleased to see the data from CheckMate-648. What was observed in this trial, LBA 4001? Dr. Jason Luke: So CheckMate-648 in esophageal cancer was a study in the frontline metastatic setting, looking at the impact of immunotherapy plus chemotherapy, or immunotherapy alone versus chemotherapy. And so what I mean by that was one arm in the study looked at nivolumab with standard chemotherapy, compared to chemotherapy, and the other arm looked at nivolumab plus ipilimumab versus chemotherapy. And, very briefly, what was observed was that both of the active arms, so the immunotherapy containing arms, the nivo plus chemotherapy or the nivo plus ipi, both of them improved outcomes compared with chemotherapy. And so, moving forward, there's really no question now that the standard of care in the frontline management of esophageal cancer should include immunotherapy, either as a combination with chemotherapy, or possibly with leaving out the chemotherapy and giving just nivolumab plus ipilimumab. Now the sub-stratification of patients and their outcomes by sub-stage was important in this study, and again emphasized that it's mostly the PD-L1 positive patients who benefited the most from immunotherapy. So but the idea of potentially having a regimen that's chemotherapy-free for frontline esophageal cancer, I think is really exciting. And I'd be really interested to follow where this field goes in terms of which patients are getting selected for the nivo chemotherapy versus ipi plus nivo arms, in standard practice kind of moving into the future. And obviously further biomarkers will be really important. But I think this is really a practice-changing trial, again, to emphasize that all patients with esophageal cancer should be getting immunotherapy in the frontline, moving forward. ASCO Daily News: Indeed, what can you tell us about Abstract 6000 using camrelizumab for nasopharyngeal carcinoma (NPC)? Dr. Jason Luke: Yeah, absolutely. So I think that this is a really interesting study and I think important. This is a study actually looking at the impact of adding immunotherapy to chemotherapy in nasopharyngeal carcinoma. So all the oncologists in the United States will be like NPC, oh, yeah, I heard about that during fellowship. But this is actually a major source of morbidity and mortality throughout the rest of the world, especially in the developing world. And so this clinical trial to me is very interesting. So the short story here is that adding camrelizumab improved outcomes relative to chemotherapy, which I think is probably not surprising, because across many other settings we've seen that adding PD-1 to chemotherapy would improve outcomes. I think the difference here was that this is an antibody that was developed in China. And is it part of a growing trend to see competitor PD-1 PD-L1 antibodies entering the space. So to close the loop on NPC, I think these data really strongly suggest that we should be giving immunotherapy in combination with chemotherapy in the frontline to these patients. But I think, more broadly, start to open this conversation about how are we going to evaluate new drugs that are getting developed, say, only in China, or in other parts of the world where there are no patients from the United States that are actually participating in the clinical trial. Are those drugs going to get approved by the U.S Food and Drug Administration (FDA)? And if they do get approved by the FDA, how are they going to get priced, because as we're moving into the era now of more than 10 anti-PD-1, PD-L1 antibodies that have shown a benefit in the metastatic setting in phase III trials, one could imagine the time has finally come for price control, and not control, but price competition. It'll be really interesting to see whether or not that actually comes true. I don't know the answer yet. But this trial, I think, is very important in that regard. ASCO Daily News: And back to melanoma, can you tell us about advances in the metastatic setting? Dr. Jason Luke: Absolutely. So I think there were two to hit on quickly. Obviously there were more, but two quickly to hit on. One was Abstract 9506, which was the long term update, 6 and a half years of CheckMate-067, which people remember was the nivolumab plus ipilimumab versus ipi trial. And just to summarize this quickly, it really was amazing to see that now at 6 and a half years, we finally hit the median for overall survival for patients with metastatic melanoma in the frontline setting. And the median was 49%. So it just barely went under the median. But I just can't emphasize, when I was a fellow, and actually I'm a melanoma oncologist, and coming into this, the outcomes for patients at that time, the median survival was 9 months. And now we're talking about 10 years later, and the median is basically, it's 6 and a half years, almost 50%. So it's just outstanding. And I can't emphasize it enough. Clearly not good enough. We still have 50% of patients who need better treatments. But it's pretty exciting. The other abstract I wanted to highlight, because I think it differentiates where things stand, was the Abstract 9505, which was the tumor infiltrating lymphocyte (TIL) lifileucil in melanoma. And, again, just to highlight this, 36.5% response rate to re-infusion of TIL with interleukin-2. And I think that that's going to be an important part of the armamentarium for melanoma management, moving into the future. One final metastatic disease abstract to highlight was the development of T cell receptor (TCR) T cells for synovial sarcoma. So this was a really important abstract as well, going along with the lifileucil abstract, because I think this showed that this is a really active regimen with adoptive cell transfer for synovial sarcoma. And I would very much expect to see that both the TCR T cells and the TIL product get approved by the FDA within the coming year. ASCO Daily News: Excellent, well, before we wrap up the podcast, can you share some highlights from your main research area, developmental therapeutics? Dr. Jason Luke: Yeah, finally, so in the realm of developmental therapeutics, which is my major research area, there's always a lot going on. And I think this year's ASCO Annual Meeting I would just highlight a few things. So one is the continued development of VEGFR2 tyrosine kinase inhibitors (TKIs) with immunotherapy, we saw long term updates with lenvatinib and pembrolizumab in melanoma (Abstract 9504). And we saw other updates with new combinations in colorectal cancer. Another area in terms of considerations were small molecule inhibitors. And so there was a really interesting abstract about an MDM2 inhibitor. And people will remember that's a regulator of P-53, being combined with pembrolizumab. And preclinically and translationally, in this abstract, it appears that modulating the P-53 pathway via MDM2 actually has immunomodulatory effects. So it'll be very interesting to see where alrizomadlin goes (Abstract 2506). There are a number of other novel targets. And there's so many abstracts on these that I'm not going to really go through them in a lot of detail. But TLR-7/8 agonism with checkpoint blockade looks interesting (Abstract 2512). There were a number of abstracts around transforming growth factor, TGF beta. And this is a really important target in cancer. And it'll be interesting to see how that gets developed out further. There were a number of approaches looking at targeting of human papillomavirus or HPV, one of them, which was a triplet regimen of an HPV vaccine plus a cytokine plus a PD-L1 antibody, and another one which was some viral vectors expressing HPV proteins. So all of this, I think, very interesting and taking sort of orthogonal to checkpoint approaches in terms of immunotherapy, vaccines, cytokines, viral vectors, et cetera. And then the final area, just to highlight, there was one very interesting Abstract 2507, which was a novel CAR T-cell product, which included a 41BB activation domain, attached actually to a bispecific CAR that binds to both CD19 and CD20. And this was Abstract 2507, and what I thought was very interesting was the rates of response for this molecule are really high, almost 100%. And that even included patients who had previously progressed on other CAR T products. So not enough time to go and give justice to any of these, but there's so much going on in developmental therapy for immuno-oncology. And I think that just emphasizes how bright the future is, building on this tremendous benefit in the standard of care setting in the adjuvant and metastatic settings. So, very excited to see where all these molecules go, and hopefully to advance the outcomes for all of our patients. ASCO Daily News: Indeed. Dr. Luke, thank you, as always, for your fantastic insight on some tremendous advances in immunotherapy, across the spectrum of malignancies. Our listeners will find links to all of the studies that you discussed in the transcript of this episode. Thank you, Dr. Luke. Dr. Jason Luke: Well, thanks so much for the opportunity. ASCO Daily News: And thanks to our listeners for joining us today. If you enjoyed this episode of the podcast, please take a moment to rate and review us wherever you get your podcasts. Disclosures: Dr. Jason Luke Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, and Arch Oncology Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, Immunocore, KSQ Therapeutics, Inzen, Pfizer, Silicon Therapeutics, TRex Bio Research Funding (Institution): Merck, Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Research Funding: Array BioPharma, Agios, Astellas Pharma, EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., Trishula Therapeutics, BioNTech AG, Scholar Rock Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof) Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

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The World of Oncology Captured In The 2020 ASCO Educational Book

Play Episode Listen Later Aug 5, 2020 13:10

Dr. John Sweetenham, medical oncologist at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center and chief editor of the ASCO Daily News, and Dr. Don Dizon, head of Women’s Cancers at Lifespan Cancer Institute in Rhode Island and editor of the ASCO Educational Book, discuss the extraordinary breadth of issues in oncology that are covered in this year’s Educational Book, which is a continuing resource for the seminal ASCO20 Virtual. Transcript Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, a medical oncologist at the UT Southwestern Simmons Cancer Center, and chief editor of ASCO Daily News. I'm pleased to be the guest host of the podcast today and to welcome my colleague, Dr. Don Dizon. He's head of women's cancers at Lifespan Cancer Institute in Rhode Island, and editor of the ASCO Educational Book. We'll discuss some of the compelling articles that have been published in the Educational Book, some of which are also going to be featured during the ASCO20 Virtual Education Program, and I'd also like to chat about important topics that perhaps aren't being covered during the program, but certainly deserve our attention. My guest and I report no conflicts of interest relating to the issues discussed in the podcast. Full disclosures relating to all Daily News podcasts are available on our episode pages. Don, it's great to have this opportunity to speak with you today. Dr Don Dizon: I'm really happy to be here. Thanks a lot. Dr. John Sweetenham: The ASCO Educational Book covers such an extraordinary breadth of issues from health services and quality improvement to symptom control, survivorship, and more. Can you tell us a little about what ASCO members can expect in the Educational Book this year? Dr. Don Dizon: Sure. I'm always happy to speak about the Educational Book. At its most germaine, what I think we have attempted to do is really live up to our ASCO President Skip Burris' vision of the approach to oncology, which is not approaching cancer with an individual's perspective, but really to bring in the multiple voices that are seminally important in everyone's experience with cancer. So we have strived very much, and our authors were exceptionally participatory in providing multidisciplinary articles on multiple cancer topics, as you just mentioned, so that the reader, who is importantly across the globe because the ASCO Educational Book is a free resource, can get that multiple perspective view on the topic related to malignancies. Dr. John Sweetenham: Can you tell us a little about some of the issues that maybe are not going to be covered in the program, but you believe are going to be very relevant to what we experience as oncologists today? Dr. Don Dizon: I think across the Educational Book, the topics that we dealt with are pretty detailed. Some of the ones that I think are of importance is a whole aspects of antibody drug conjugates, for example, which is covered in the developmental therapeutics track of the Educational Book, and there are multiple perspectives going from the basics of ADCs, all the way up to the clinical application of, not only FDA approved ones, but others that are in development. So that's very important, I believe. Global oncology is also covered, and although most of us are practicing perhaps in the United States, we have attempted to bring in multiple voices internationally because we recognize that ASCO serves an international audience, and its members are not limited to the United States. In the area of breast oncology, we attempted to really cover multiple topics that are relevant across the continuum of breast cancer, really paying attention to what subgroups are guiding therapy these days, whether that be the hormone positive subset, triple negative, the role of the immunotherapy, but also the approaches to metastatic breast cancer. So I believe that all throughout the Educational Book, you will find topics that are relevant, not only to the specialist, for a more contemporary view of where the field is at, but also very relevant for our folks who are in practice in our communities. Dr. John Sweetenham: Great, thank you, and I think one of the real strengths of the Educational Book is that it covers many of those topics that I would say we think about some of the time, but maybe we should be thinking of a little bit more. I'm thinking specifically of adolescent and young adults with cancer, fertility problems associated with cancer and its treatments, and then some of these 'softer issues,' such as communication with our patients, and more primary palliative care. Can you comment on some of those areas that are going to be covered in the Educational Book this year? Dr. Don Dizon: Yeah, absolutely, I think you had mentioned the issues concerning adolescents and young adults (with cancer), and certainly there are topics that are relevant for folks that we are hoping to cure and potentially are going to be alive for many, many decades. And I think for those folks, we do want to question the importance of addressing issues when we first meet them, rather than saving them for end of treatment, or even four or five years later. A classic example of that is fertility preservation, but equally important is the topic of sexual health in these patients, and I am very fortunate that our AYA topics did deal with these issues that aren't routinely discussed, but hopefully, this will really push our colleagues to embrace that these are important aspects. Same thing goes with palliative care, and the role of the oncologists in the delivery of care, particularly for patients who are not dealing with curative intent illness. And so I think the Educational Book, not only summarizes the field, but with multiple people generating that manuscript really drives home an action item, which again, is one of the things we were pretty cognizant about because at that end of the day, it's nice to have a summary, but it's more important to provide guidance. Dr. John Sweetenham: One of the other aspects of the Education Program as a whole that I really like this year is that I think that you and ASCO are tackling some issues which are a little more almost edgy and controversial, and I'm thinking in particular around issues such as disparities in access to care, gender disparities in the oncology workforce, which I think is a really interesting subject to address, and then some of my own kind of pet controversies, I guess, such as the use of real world data and cancer center advertising, which I think are all intriguing subjects to be covered in the Education Program. Can you comment just a little on how you decided to include those topics this year? Dr. Don Dizon: You know I will credit the Education Committee for branching out just beyond the science of oncology and really going into the practice, as well as the art of oncology. The Educational Book and the topics we cover are only as reflective of what the society feels is important for that annual meeting. And I think in this regard, leadership really did embrace a broad range of topics and tried to achieve one important aspect across all of them, health equity and the approach to patients no matter who they are and who they love and how they identify themselves in terms of health equity, it was all about achieving balance, in terms of who was invited to speak, who wrote articles for and with us, and also the way the language of the Educational Book was structured is very deliberate. We wanted to make a stance that there is a better way to write about oncology, and there's a better way to speak with each other. And I think you'll see this reflected, not only in the Education Session virtually, but hopefully you'll see that also approach in the Educational Book. So the book is a continuing resource, I think, for this seminal Education Program that was put together for 2020. Sadly, circumstances today led to the cancellation of the in-person meeting, but I think the Education Program virtually is going to be reflective of this exceptionally all encompassing view of oncology practice. Fortunately, the Education Program will live on for 2020 within the Educational Book. Dr. John Sweetenham: All right, thank you. You mentioned this extraordinary time. The moment in August of 2020. It's difficult to talk about oncology and not bring up the issue of COVID-19 and the pandemic. Can we expect to see that addressed in the Education Program this year? Dr. Don Dizon: The answer shortly is yes. The fact that the Education Program really worked to identify and address very contemporary issues is an important aspect of how reactive the program has had to be. So there are two sessions in the Education Program which are going to be really important, I think, for all of us. One from the trainees perspective and how programs are managing COVID-19's presence as we train the next generation of oncologists in our fellowship programs, this has, I'm sure, John, you feel the same. It did impact the program here at Brown University, as it did, I'm sure, all across the country, and it's impacting how we select fellows for the coming year. Given that not everybody is able, willing, or should travel to meet with programs. So virtual interviews are on the horizon, and I think hearing from program directors about how they are going to manage that virtual aspect of interviewing, and more importantly, advice to people who are interviewing is going to be as important. I think one of the quickest collaborations in the history of medicine, especially oncology, was around COVID-19 and cancer, and there will also be a roundtable on that specific issue that is going to be a part of the Education Sessions this year. Dr. John Sweetenham: Yeah, I guess I hadn't really thought of it so much, but I guess that virtual interviews may require a very different skill set from the ones we use for our in-person interviews, right? Dr. Don Dizon: I think it will be. I'm a big advocate for social media, for example, but people have critiqued your background. Where you are selecting to do the interview might be important for program directors to get a better sense of who you are, but it also behooves us as clinicians to appear professionally as well when we're representing our programs. Dr. John Sweetenham: Right, absolutely. Well, it's difficult to believe, but I think that we are just coming to the end of our time. Don, thank you for your time. It's been a real pleasure listening to you, and I just want to say congratulations on what I think is an outstanding Education Program. Very, very, very broad, and I think we're all going to learn a lot this year. Dr. Don Dizon: Thank you so much, John. It's always a pleasure to speak with you. Hopefully, next year we'll be in person. Just one other shout out that for the Education Program, just for everyone who's attending, 74% of the sessions that are going to be presented have a companion Educational Book article, and I'm exceptionally proud of that. Thank you very much, John. Dr. John Sweetenham: Thank you. That's outstanding, and thanks to our listeners for joining us today. Please take a moment to rate and review us on Apple Podcasts. Thanks again, and goodbye. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. COI Disclosures: Dr. John Sweetenham Honoraria: Seattle Genetics Dr. Don Dizon Stock and Ownership Interests: InfiniteMD, NeuHope Consulting/Advisory: i-Mab, Clovis Oncology, AstraZeneca, Regeron, Tesaro, Merck, Sharp & Dohme, Bristol-Myers Squibb, Kazia Pharmaceuticals

BTB: Jane Wilkens Michael talks Avenging Ovarian Cancer with Cobie Smulders

Play Episode Listen Later Aug 1, 2019 30:17

Jane’s guest today is the sensational Cobie Smulders, a Canadian superstar who became universally known in America as Robin Sherbatzky on CBS’s long-running How I Met Your Mother, on S.H.I.E.L.D as Honcho Maria Hill, and as Lisa in the Netflix comedy Friends from College. In moviedom, she stars in the Avenger series --- including the upcoming Spider-Man: Far From Home. But what her legions of fans might not know about Cobie, is that at the age of 25, she was faced with a shocking diagnosis of ovarian cancer. Shortly after, she underwent several surgeries and has now been in remission for more than 10 years. Cobie’s experience as a successful survivor is still quite unusual. Many women don’t know they even have ovarian cancer until it’s already in advanced stages. Unfortunately, the majority will see it return. Understanding the need for education among women with this type of cancer, Cobie has partnered with TESARO, an oncology-focused biopharmaceutical company, on a campaign called “Not on My Watch.” They have combined, in a nationwide movement, to empower women with recurrent ovarian cancer to take proactive steps in managing their disease by making informed decision with their healthcare providers about their treatments. On this segment with Jane, Cobie, wife of TV star Taran Killam and mother of two young daughters, speaks about her experience with ovarian cancer, her advice for others, as well as her inspiring public service announcement she both directed and starred in that benefits survivors of any cancer. Furthermore, she shares the personal lifestyle tips and tools that keep her happy, healthy, and Better Than Before.

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BTB: Jane Wilkens Michael Show talks with Golden Girl - Shannon Miller

To Your Good Health Radio

Play Episode Listen Later Jun 13, 2019 29:45

A talk with legendary Olympic gymnast Shannon Miller - Gymnasts are known for their strength, agility, flexibility, coordination and determination. And no one embodies all five star qualities better than the remarkable Shannon Miller. Indeed, she is the most decorated U.S. gymnast, male or female, in the history of the Olympic Games, with seven gold medals to her name. And with a combined total of 16 World Championships and Olympic medals, she is the second most decorated gymnast in U.S. history, as well. However, with all the glory came a challenge that rivaled her athletic accomplishments. In 2011, when she was only in her early thirties and a young mother, her doctor discovered a baseball-sized growth on her ovary, which was later diagnosed as ovarian cancer. However, thanks to her true Olympian work ethic and attitude, today this superstar, who is also an author and TV host, is not only a survivor but a thriver, adding ovarian cancer awareness advocate to her long list of achievements. Through her role in the Our Way Forward program, on which she has partnered with the oncology-focused biopharmaceutical company Tesaro, she is helping other women learn more about their disease and their options, as they navigate the difficult journey of ovarian cancer diagnosis, treatment, recurrence and finding their new normal. On this segment, Shannon talks about her campaign, and gives her personal lifestyle regimen and tips on overcoming adversity to look and feel Better Than Before.

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The Care Partner Perspective of Recurrent Ovarian Cancer, with Actor Scott Foley

Play Episode Listen Later Mar 14, 2019

Celebrated actor Scott Foley discusses the Not My Watch movement and how its helping women suffering from recurrent ovarian cancer.Scott Foley is a celebrated TV and film star, most known for his appearance on shows like Scandal, Felicity, and the new ABC show, Whiskey Cavalier. What many do not know is that one of Scott’s biggest roles happened off-screen and at an early age, when he acted as a secondary caregiver to his mother during her time with recurrent ovarian cancer. Scott helped his mom through multiple recurrences for four years before losing her to the devastating disease when he was 15. At the time, treatment options were limited and much time was spent watching and waiting for the cancer to come back. Now, women with recurrent ovarian cancer, who have responded to platinum-based chemotherapy, have options called maintenance therapies that can extend their time in response and delay recurrence. Still nearly 50% of eligible women are not receiving or not aware of these options. To help get the word out, Scott has partnered with TESARO, an oncology-focused bio-pharmaceutical company, on "Not on My Watch," a nationwide movement that seeks to inform and empower women with recurrent ovarian cancer and their care partners to take proactive steps in managing the disease, like talking to their healthcare provider about maintenance therapy. As part of the Not on My Watch movement, Scott stars in an educational Public Service Announcement that reveals, for the first time, his very personal story.Listen as Scott joins Dr. Friedman to share more information about the movement.Watch Scott's PSA HERE

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BTB: Jane Wilkens Michael Show talks Great Scott

Play Episode Listen Later Mar 6, 2019 27:12

A conversation with Whiskey Cavalier’s Scott Foley - Whiskey Cavalier, which premiered right after the Oscars on ABC TV, is already one of the most buzzed about new shows this season. In it, Scott Foley, formerly a star of such hit dramas as Scandal and Felicity, plays Will Chase, an FBI agent who is redefining the role of an action hero. Indeed, this tough supercop is both empathetic and emotionally aware. Yet while critically acclaimed for his television, film and Broadway acting, what many of his fans may not know about Scott is that one of his most important roles happened off-screen and at an early age, when he acted as a secondary caregiver to his mother during her time with recurrent ovarian cancer, sadly losing her when he was fifteen. It is the reason he has now partnered with TESARO, an oncology-focused biopharmaceutical company, in getting the word out about Not on My Watch, an important nationwide movement that seeks to inform and empower women with ovarian cancer and their care partners to take proactive steps in managing the disease. In this segment, Jane and Scott talk about his new show which he helped create, his family, and his not-to-be-missed lifestyle advice and fitness secrets -- after all, at age 46, he still does many of his own stunts in the show! He also discusses the educational Public Service Announcement he made with TESARO that reveals, for the first time, his very personal story. In addition, Scott and Jane share take-away tips for both survivors and caregivers to help them look and feel Better Than Before.

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9: Scott Foley Opens Up About Caregiving

CURE Talks Cancer

Play Episode Listen Later Feb 28, 2019 14:35

For 25-plus years, we’ve watched Scott Foley in a variety of acting roles – on shows like “Felicity,” “Scandal” and now “Whiskey Cavalier” – but many don’t know about his role as a caregiver to his mother after she received an ovarian cancer diagnosis when he was just 11. Following his experience, Scott has teamed up with Tesaro as part of the Not on My Watch movement to share his story in hopes of educating others about treatments advances in ovarian cancer and why women no longer have to just watch and wait if their disease recurs. With each share of Scott’s public service announcement, Tesaro will donate $5 to ovarian cancer patient organizations and support programs. For more information and to watch the video, visit [notonmywatch.com](https://www.notonmywatch.com/).

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BTB: Jane Wilkens Michael talks Avenging Ovarian Cancer with Cobie Smulders

Rare Disease, Cell & Gene Therapy Weekly RoundUp

Play Episode Listen Later Feb 21, 2019 30:17

Jane’s guest today is the sensational Cobie Smulders, a Canadian superstar who became universally known in America as Robin Sherbatzky on CBS’s long-running How I Met Your Mother, on S.H.I.E.L.D as Honcho Maria Hill, and as Lisa in the Netflix comedy Friends from College. In moviedom, she stars in the Avenger series --- including the upcoming Spider-Man: Far From Home. But what her legions of fans might not know about Cobie, is that at the age of 25, she was faced with a shocking diagnosis of ovarian cancer. Shortly after, she underwent several surgeries and has now been in remission for more than 10 years. Cobie’s experience as a successful survivor is still quite unusual. Many women don’t know they even have ovarian cancer until it’s already in advanced stages. Unfortunately, the majority will see it return. Understanding the need for education among women with this type of cancer, Cobie has partnered with TESARO, an oncology-focused biopharmaceutical company, on a campaign called “Not on My Watch.” They have combined, in a nationwide movement, to empower women with recurrent ovarian cancer to take proactive steps in managing their disease by making informed decision with their healthcare providers about their treatments. On this segment with Jane, Cobie, wife of TV star Taran Killam and mother of two young daughters, speaks about her experience with ovarian cancer, her advice for others, as well as her inspiring public service announcement she both directed and starred in that benefits survivors of any cancer. Furthermore, she shares the personal lifestyle tips and tools that keep her happy, healthy, and Better Than Before.

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Weekly Roundup: January 11, 2019

Play Episode Listen Later Jan 14, 2019 6:41

Happy New Year to Weekly Roundup listeners! 2019 is shaping up to be an exciting year for the healthcare and biotechnology industry. We are only a couple of weeks in and already news developments are buzzing on the regulatory and corporate front. So for this week's episode, we start by discussing the recent wave of mergers and acquisition deals announced by Big Pharma namely, Eli Lilly and Loxo; BMS and Celgene as well as GSK and Tesaro. Also, the P4A team look at the implications of the current US government shutdown on the FDA and the agency's initiative on assessments for innovative drugs. Presenter : Max Rex Contributor : Joanna Fernandes Producer: Aparna Krishnan

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Pharmapills puntata n. 77. Aumenta la spesa farmaceutica mondiale

Play Episode Listen Later Dec 12, 2018 12:27

PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Azienda: Gsk, Tesaro, Takeda, Shire, Merck, FDA, Novimmune, IQVIA, Worldwide Clinical Trials, PPD.Persone: Hal Barron (Gsk), Gloria Dalla Costa (Ospedale San Raffaele di Milano), Donatella Mattia (Irccs Fondazione Santa Lucia di Roma).Nuove terapie: niraparib, emapalumab.Patologie: tumore ovarico, sclerosi multipla, linfoistiocitosi emofagocitica primaria.Lavoro: Clinica Research Associate.Il mercoledì alle h 12.00 su Spreaker.com e iTunes.Seguici su: www.telegram.me/pharmapillswww.facebook.com/pharmapills/

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Pharmapills puntata n. 77. Aumenta la spesa farmaceutica mondiale

Play Episode Listen Later Dec 12, 2018 12:27

PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Azienda: Gsk, Tesaro, Takeda, Shire, Merck, FDA, Novimmune, IQVIA, Worldwide Clinical Trials, PPD.Persone: Hal Barron (Gsk), Gloria Dalla Costa (Ospedale San Raffaele di Milano), Donatella Mattia (Irccs Fondazione Santa Lucia di Roma).Nuove terapie: niraparib, emapalumab.Patologie: tumore ovarico, sclerosi multipla, linfoistiocitosi emofagocitica primaria.Lavoro: Clinica Research Associate.Il mercoledì alle h 12.00 su Spreaker.com e iTunes.Seguici su: www.telegram.me/pharmapillswww.facebook.com/pharmapills/

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How Tesaro is Integrating the Patient in the Clinical Development Process

PharmaTalkRadio

Play Episode Listen Later Dec 12, 2018 26:00

In this talk from the 5th annual Patients as Partners US conference, Beth Zaharoff, Director, Patient-Focused Clinical Trial Engagement of Tesaro will walk the audience through how they integrated patient input throughout multiple stages of the development process. Other discussion points include: How Tesaro is working to eliminate some of the burdens inherent in clinical trial participationWhat patient focus means to Tesaro and why/how they decided to jump in the deep endTesaro focus groups and what they learned from the experts Join us this year at the 6th annual Patients as Partners US conference, taking place March 11-12, 2019 in Philadelphia.

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Shell ties exec pay to carbon footprint, GlaxoSmithKline buys Tesaro & Qatar drops out of OPEC

The Water Coolest

Play Episode Listen Later Dec 4, 2018 2:05

In today's Minutes: Shell will tie its executives pay to the company's carbon footprint going forward, GlaxoSmithKline buys Tesaro for $5.1B, and Qatar announces it is leaving OPEC. Plus, get your Bill Gates on. --- Support this podcast: https://anchor.fm/watercoolesthq/support

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How I Met Your Mother Cobie Smulders on Ovarian Cancer

GUSH

Play Episode Listen Later Oct 26, 2018 9:32

We all know and love Cobie Smulders in her roles as Robin Scherbatsky on How I Met Your Mother and as Maria Hill on the big screen film, Avengers. What may surprise you is that she was diagnosed with ovarian cancer when she was 25 years old. Cobie knows firsthand the emotional toll the disease and the high threat of recurrence can take on women and their loved ones. She has partnered with biopharma company Tesaro and directed a PSA for Not on My Watch https://www.notonmywatch.com to empower women with recurrent ovarian cancer to take a proactive role in managing their disease. Each time Cobie's PSA is shared on social media, Tesaro will donate $5 to ovarian cancer patient organizations! So, please share! Cobie is joined by Dr. Amina Ahmed, Visit www.MD.com/doctor/amina-ahmed-1-md for information about Dr. Amina Ahmed, Gynecologic Oncologist in Illinois.

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39: Cobie Smulders: Not on My Watch

CURE Talks Cancer

Play Episode Listen Later Oct 24, 2018 11:35

Actress, director and ovarian cancer survivor Cobie Smulders – best known for her roles in How I Met Your Mother and The Avengers series – has partnered with TESARO to launch the national movement, Not on My Watch, to help empower the ovarian cancer community. At the age of 25, Cobie was diagnosed with ovarian cancer after advocating for herself to get an ultrasound that led to her diagnosis. Now, recurrence-free more than 10 years later, she knows that the majority of women with ovarian cancer will see the disease return. So, she is working to educate women to let them know they no longer have to just "watch and wait." Through the initiative, TESARO will donate $5 to ovarian cancer patient organizations every time Cobie’s public service announcement video is shared. To learn more or to share the video, visit [https://www.notonmywatch.com/](https://www.notonmywatch.com/)

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38: Illuminating Ovarian Cancer

CURE Talks Cancer

Play Episode Listen Later Oct 19, 2018 14:22

Storytelling can help others feel empowered and encourages the narrative around hope for many. Last month, Tesaro partnered with The Moth, an organization that promotes the art and craft of storytelling, to host a special event called “Our Way Forward: Stories that Illuminate the Ovarian Cancer Experience.” In this episode of CURE Talks Cancer, we caught up with all three storytellers from the event who shared their experiences with recurrent ovarian cancer.

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FirstWord Pharmaceutical News for Thursday, June 21 2018

Play Episode Listen Later Jun 21, 2018 2:23

Today in FirstWord:

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FirstWord Pharmaceutical News for Tuesday, June 13 2017

Play Episode Listen Later Jun 13, 2017 1:49

Today in FirstWord:

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Pharmapills puntata n.8. PRA HS vince il premio CRO del 2017 di PharmaTimes

Play Episode Listen Later May 10, 2017 15:02

PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Aziende: AIFA, EMA, Merk, Celgene, PRA Health Sciences, Novartis, Tesaro.Persone: Beatrice Lorenzin (Ministro della Salute), Claudio Vincelli (Generale NAS), Mario Melazzini (AIFA), Alessandra Aloe (Merk, Ssfa), Antonio Messina (Merk), Jean-Yves Chatelan (Celgene), Walter Ricciardi (ISS), Michele D’Alto (AO Monaldi Di Napoli), Leonardo Radicchi (AIPI), Vittorio Vivenzio (AMIP), Carmine Dario Vizza (Università ‘La Sapienza’ di Roma), Michele Senni (Ospedale Papa Giovanni XXIII di Bergamo), Giuseppe Maiocchi (Novartis), Roberto Florenzano (Tesaro).Nuove terapie: alemtuzumab, Entresto, rolapitant, nivolumab.Patologie: obesità, ipertensione polmonare, sclerosi multipla, scompenso cardiaco, nausea e vomito indotti da chemioterapia (CINV), tumore testa-collo a cellule squamose.Ogni mercoledì alle h 12.00 su Spreaker.com e iTunes.Seguici su: www.telegram.me/pharmapillswww.facebook.com/pharmapills/

roma salute spreaker cro premio ogni lavoro novartis merk nuove bergamo novit curiosit seguici aifa la sapienza celgene patologie entresto lorenzin tesaro cinv

Pharmapills puntata n.8. PRA HS vince il premio CRO del 2017 di PharmaTimes

Play Episode Listen Later May 10, 2017 15:02

PharmaPills - Pillole dal farmaceutico: Novità, Curiosità e Lavoro dal mondo del farmaceutico. A cura di Stefano LagravineseIn questa puntata parliamo di:Aziende: AIFA, EMA, Merk, Celgene, PRA Health Sciences, Novartis, Tesaro.Persone: Beatrice Lorenzin (Ministro della Salute), Claudio Vincelli (Generale NAS), Mario Melazzini (AIFA), Alessandra Aloe (Merk, Ssfa), Antonio Messina (Merk), Jean-Yves Chatelan (Celgene), Walter Ricciardi (ISS), Michele D’Alto (AO Monaldi Di Napoli), Leonardo Radicchi (AIPI), Vittorio Vivenzio (AMIP), Carmine Dario Vizza (Università ‘La Sapienza’ di Roma), Michele Senni (Ospedale Papa Giovanni XXIII di Bergamo), Giuseppe Maiocchi (Novartis), Roberto Florenzano (Tesaro).Nuove terapie: alemtuzumab, Entresto, rolapitant, nivolumab.Patologie: obesità, ipertensione polmonare, sclerosi multipla, scompenso cardiaco, nausea e vomito indotti da chemioterapia (CINV), tumore testa-collo a cellule squamose.Ogni mercoledì alle h 12.00 su Spreaker.com e iTunes.Seguici su: www.telegram.me/pharmapillswww.facebook.com/pharmapills/

roma salute spreaker cro premio ogni lavoro novartis merk nuove bergamo novit curiosit seguici aifa la sapienza celgene patologie entresto lorenzin tesaro cinv

FirstWord Pharmaceutical News for Tuesday, Mar 28 2017

Play Episode Listen Later Mar 28, 2017 1:58

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FirstWord Pharmaceutical News for Thursday, Feb 9, 2017

Play Episode Listen Later Feb 9, 2017 1:43

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FirstWord Pharmaceutical News for Friday, Jan 13, 2017

Stock Market Mentor Chart of the Day

Play Episode Listen Later Jan 13, 2017 1:24

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Here's how you trade Clovis Oncology (CLVS) and Tesaro (TSRO). (December 19, 2016)

Play Episode Listen Later Dec 19, 2016

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FirstWord Pharmaceutical News for Tuesday, December 24, 2013