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Dr. John Sweetenham and Dr. Erika Hamilton highlight key abstracts that were presented at ASCO25, including advances in breast and pancreatic cancers as well as remarkable data from the use of structured exercise programs in cancer care. Transcript Dr. Sweetenham: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. John Sweetenham. Today, we'll be discussing some of the key advances and novel approaches in cancer care that were presented at the 2025 ASCO Annual Meeting. I'm delighted to be joined again by the chair of the Meeting's Scientific Program, Dr. Erika Hamilton. She is a medical oncologist and director of breast cancer and gynecologic cancer research at the Sarah Cannon Research Institute in Nashville, Tennessee.  Our full disclosures are available in the transcript of this episode. Dr. Hamilton, congratulations on a fantastic meeting. From the practice-changing science to the world-renowned speakers at this year's Meeting, ASCO25 really reflected the amazing progress we're seeing in oncology today and the enormous opportunities that lie ahead of us. And thanks for coming back on to the podcast today to discuss some of these advances. Dr. Hamilton: Thanks, Dr. Sweetenham. I'm happy to join you today. It really was an impactful ASCO Annual Meeting. I probably am biased, but some great research was presented this year, and I heard lots of great conversations happening while we were there. Dr. Sweetenham: Yeah, absolutely. There was a lot of buzz, as well as a lot of media buzz around the meeting this year, and I think that's probably a good place to start. So I'd like to dive into abstract number LBA3510. This was the CHALLENGE trial, which created a lot of buzz at the meeting and subsequently in the media. This is the study that was led by the NCI Canada Clinical Trials Group, which was the first randomized phase 3 trial in patients with stage III and high-risk stage II colon cancer, which demonstrated that a post-treatment structured exercise program is both feasible and effective in improving disease-free survival in this patient group. The study was performed over a long period of time and in many respects is quite remarkable. So, I wonder if you could give us your thoughts about this study and whether you think that this means that our futures are going to be full of structured exercise programs for those patients who may benefit. Dr. Hamilton: It's a fantastic question. I think that this abstract did create a lot of buzz. We were very excited when we read it. It was highlighted in one of the Clinical Science Symposium sessions. But briefly, this was a phase 3 randomized trial. It was conducted at 55 centers, so really a broad experience, and patients that had resected colon cancer who completed adjuvant therapy were allowed to participate. There were essentially 2 groups: a structured exercise program, called ‘the exercise group,' or health education materials alone, so that was called just ‘the health education group.' And this was a 3-year intervention, so very high quality. The primary end point, as you mentioned, was disease-free survival. This actually accrued from 2009 to 2024, so quite a lift, and almost 900 patients underwent randomization to the exercise group or the health education group. And at almost 8 years of follow-up, we saw that the disease-free survival was significantly longer in the exercise group than the health education group. This was essentially 80.3% of patients were disease-free in exercise and 73.9% in the health education group. So a difference of over 6 percentage points, which, you know, at least in the breast cancer world, we make decisions about whether to do chemotherapy or not based on these kind of data. We also looked at overall survival in the exercise group and health education group, and the 8-year overall survival was 90.3% in the exercise group and 83.2% in the health education group. So this was a difference of 7.1%. Still statistically significant. I think this was really a fantastic effort over more than a decade at over 50 institutions with almost 900 patients, really done in a very systematic, high-intervention way that showed a fantastic result. Absolutely generalizable for patients with colon cancer. We have hints in other cancers that this is beneficial, and frankly, for our patients for other comorbidities, such as cardiovascular, etc., I really think that this is an abstract that deserved the press that it received. Dr. Sweetenham: Yeah, absolutely, and it is going to be very interesting, I think, over the next 2 or 3 years to see how much impact this particular study might have on programs across the country and across the world actually, in terms of what they do in this kind of adjuvant setting for structured exercise. Dr. Hamilton: Absolutely.  So let's move on to Abstract 3006. This was an NCI-led effort comparing genomic testing using ctDNA and tissue from patients with less common cancers who were enrolled in but not eligible for a treatment arm of the NCI-MATCH trial. Tell us about your takeaways from this study. Dr. Sweetenham: Yeah, so I thought this was a really interesting study based, as you said, on NCI-MATCH. And many of the listeners will probably remember that the original NCI-MATCH study screened almost 6,000 patients to assess eligibility for those who had an actionable mutation. And it turned out that about 60% of the patients who went on to the study had less common tumors, which were defined as anything other than colon, rectum, breast, non–small cell lung cancer, or prostate cancer. And most of those patients lacked an eligible mutation of interest and so didn't get onto a trial therapy. But with a great deal of foresight, the study group had actually collected plasma samples from these patients so that they would have the opportunity to look at circulating tumor DNA profiles with the potential being that this might be another way for testing for clinically relevant mutations in some of these less common cancer types. So initially, they tested more than 2,000 patients, and to make a somewhat complicated story short, there was a subset of five histologies with a larger representation in terms of sample size. And these were cholangiocarcinoma, small cell lung cancer, esophageal cancer, pancreatic, and salivary gland cancer. And in those particular tumors, when they compared the ctDNA sequencing with the original tumor, there was a concordance there of around 84%, 85%. And in the presentation, the investigators go on to list the specific mutated genes that were identified in each of those tumors. But I think that the other compelling part of this study from my perspective was not just that concordance, which suggests that there's an opportunity there for the use of ctDNA instead of tumor biopsies in some of these situations, but what was also interesting was the fact that there were several clinically relevant mutations which were detected only in the circulating tumor DNA. And a couple of examples of those included IDH1 for cholangiocarcinoma, BRAF and p53 in several histologies, and microsatellite instability was most prevalent in small cell lung cancer in the ctDNA. So I think that what this demonstrates is that liquid biopsy is certainly a viable screening option for patients who are being assessed for matching for targeted therapies in clinical trials. The fact that some of these mutations were only seen in the ctDNA and not in the primary tumor specimen certainly suggests that there's some tumor heterogeneity. But I think that for me, the most compelling part of this study was the fact that many of these mutations were only picked up in the plasma. And so, as the authors concluded, they believe that a comprehensive gene profiling with circulating tumor DNA probably should be included as a primary screening modality in future trials of targeted therapy of this type. Dr. Hamilton: Yeah, I think that that's really interesting and mirrors a lot of data that we've been seeing. At least in breast cancer, you know, we still do a biopsy up front to make sure that our markers, we're still treating the right disease that we think we are. But it really speaks to the utility of using ctDNA for serial monitoring and the emergence of mutations. Dr. Sweetenham: Absolutely. And you mentioned breast cancer, and so I'd like to dwell on that for a moment here because obviously, there was a huge amount of exciting breast cancer data presented at the meeting this year. And in particular, I'd like to ask you about LBA1008, the DESTINY-Breast09 clinical trial, which I think has the potential to establish a new first-line standard of care for metastatic HER2+ breast cancer. And that's an area where we haven't seen a whole lot of innovation for around a decade now. So can you give us some of the highlights of this trial and what your thinking is, having seen the results? Dr. Hamilton: Yeah, absolutely. So this was a trial in the first-line metastatic HER2 setting. So this was looking at trastuzumab deruxtecan. We certainly have had no shortage of reports around this drug, initially approved for later lines. DESTINY-Breast03 brought it into our second-line setting for HER2+ disease and we're now looking at DESTINY-Breast09 in first-line. So this actually was a 3-arm trial where patients were randomized 1:1:1 against standard taxane/trastuzumab/pertuzumab in one arm; trastuzumab deruxtecan with pertuzumab in another arm; and then a third arm, trastuzumab deruxtecan alone. And what we did not see reported was that trastuzumab deruxtecan-alone arm. But we did have reports from the trastuzumab deruxtecan plus pertuzumab versus the chemo/trastuzumab/pertuzumab. And what we saw was a statistically significant improvement in median progression-free survival, 26.9 months up to 40.7, so an improvement of 13.8 months, over a year in PFS. Not to mention that we're now in the 40-month range for PFS in first-line disease. Really, across all subgroups, we really weren't able to pick out a subset of patients that did not benefit. We did see about a 12% ILD rate with trastuzumab deruxtecan. That really is on par with what we've seen in other studies, around 10%-15%. I think that this is going to become a new standard of care in the first-line. I think it did leave some unanswered questions. We saw some data from the PATINA trial this past San Antonio Breast, looking at the addition of endocrine therapy with or without a CDK4/6 inhibitor, palbociclib, for those patients that also have ER+ disease, after taxane has dropped out in the first-line setting. So how we're going to kind of merge all this together is, I suspect that there are going to be patients that we or they just don't have the appetite to continue 3 to 4 years of trastuzumab deruxtecan. And so we're probably going to be looking at a maintenance-type strategy for them, maybe integrating the PATINA data there. But how we really put this into practice in the first-line setting and if or when we think about de-escalating down from trastuzumab deruxtecan to antibody therapy are some lingering questions. Dr. Sweetenham: Okay, so certainly is going to influence practice, but watch this space for a little bit longer, it sounds as though that's what you're saying. Dr. Hamilton: Absolutely.  So let's move on to GI cancer. Abstract 4006 reported preliminary results from the randomized phase 2 study of elraglusib in combination with gemcitabine/nab-paclitaxel versus the chemo gemcitabine/nab-paclitaxel alone in patients with previously untreated metastatic pancreatic cancer. Can you tell us more about this study? Dr. Sweetenham: Yeah, absolutely. As you mentioned, elraglusib is actually a first-in-class inhibitor of GSK3-beta, which has multiple potential actions in pancreatic cancer. But the drug itself may be involved in mediating drug resistance as well as in some tumor immune response modulation. Some of that's not clearly understood, I believe, right now. But certainly, preclinical data suggests that the drug may be effective in preclinical models and may also be effective in combination with chemotherapy and potentially with immune-modulating agents as well. So this particular study, as you said, was an open-label, randomized phase 2 study in which patients with pancreatic cancer were randomized 2:1 in favor of the elraglusib plus GMP—gemcitabine and nab-paclitaxel—versus the chemotherapy alone. And upon completion of the study, which is not right now, median overall survival was the primary end point, but there are a number of other end points which I'll talk about in just a moment. But the sample size was planned to be around 207 patients. The primary analysis included 155 patients in the combination arm versus 78 patients in the gemcitabine/nab-paclitaxel arm. Overall, the 1-year overall survival rate was 44.1% for the patients in the elraglusib-containing arm versus 23.0% in the patients receiving gemcitabine/nab-paclitaxel only. When they look at the median overall survival, it was 9.3 months for the experimental arm versus 7.2 months for chemotherapy alone. So put another way, there's around a 37% reduction in the risk of death with the use of this combination arm. The treatment was overall well-tolerated. There were some issues with grade 1 to 2 transient visual impairment in a large proportion of the patients. The most common treatment-related adverse effects with the elraglusib/GMP combination was transient visual impairment, which affected around 60% of the patients. Most of the more serious treatment-related adverse events included neutropenia, anemia, and fatigue in 50%, 25%, and 16% of the patients, respectively. So the early results from this study show a significant benefit for 1-year overall survival and for median overall survival with, as I mentioned above, a significant reduction in the risk of death. The authors went on to mention that the median overall survival for the control arm in this study is somewhat lower than in other comparable trials, but they think that this may be related to a more advanced disease burden in this particular study. Of interest to me was that right now: there is no apparent difference in progression-free survival between the 2 arms of this study. The authors described this as potentially indicating that this may be related in some way to immune modulation and immune effects on the tumor, which, if I'm completely honest, I don't totally understand. And so, the improvement in overall survival, as far as I can see at the moment, is not matched by an improvement in progression-free survival. So I think we probably need to wait for more time to elapse to see what happens with the study. And so, I think it certainly is an interesting study, and the results are intriguing, but I think it's probably a little early for it to actually shift the treatment paradigm in this disease. Dr. Hamilton: Fantastic. I think we've been waiting for advances in pancreatic cancer for a long time, but this, not unlike others, we learn more and then learn more we don't realize, so. Dr. Sweetenham: Right. Let's shift gears at this point and talk about a couple of other abstracts in kind of a very different space. Let's start out with symptom management for older adults with cancer. We know that undertreated symptoms are common among the older patient population, and Abstract 11002 reported on a randomized trial that demonstrated the effects of remote monitoring for older patients with cancer in terms of kind of symptoms and so on. Can you tell us a little bit about this study and whether you think this approach will potentially improve care for older patients? Dr. Hamilton: Yeah, I really liked this abstract. It was conducted through the Veterans Affairs, and it was based in California, which I'm telling you that because it's going to have a little bit of an implication later on. But essentially, adults that were 75 years or older who were Medicare Advantage beneficiaries were eligible to participate. Forty-three clinics in Southern California and Arizona, and patients were randomized either into a control group of usual clinic care alone, or an intervention group, which was usual care plus a lay health worker-led proactive telephone-based weekly symptom assessment, and this was for 12 months using the validated Edmonton Symptom Assessment System. So, there was a planned enrollment of at least 200 patients in each group. They successfully met that. And this lay health worker reviewed assessments with a physician assistant, who conducted follow-up for symptoms that changed by 2 points from a prior assessment or were rated 4 or greater. So almost a triage system to figure out who needed to be reached out to and to kind of work on symptoms. What I thought was fantastic about this was it was very representative of where it enrolled. There were actually about 50% of patients enrolled here that were Hispanic or Latinos. So some of our underserved populations and really across a wide variety of tumor types. They found that the intervention group had 53% lower odds of emergency room use, 68% lower odds of hospital use than the control group. And when they translated this to actual total cost of care, this was a savings of about $12,000 U.S. per participant and 75% lower odds of a death in an acute care facility. So I thought this was really interesting for a variety of reasons. One, certainly health care utilization and cost, but even more so, I think any of our patients would want to prevent hospitalizations and ER visits. Normally, that's not a fantastic experience having to feel poorly enough that you're in the emergency room or the hospital. And really showing in kind of concrete metrics that we were able to decrease this with this intervention. In terms of sustainability and scalability, I think the question is really the workforce to do this. Obviously, you know, this is going to take dedicated employees to have the ability to reach out to these patients, etc., but I think in value-based care, there's definitely a possibility of having reimbursement and having the funds to institute a program like this. So, definitely thought-provoking, and I hope it leads to more interventions. Dr. Sweetenham: Yeah, we've seen, over several years now, many of these studies which have looked at remote symptom monitoring and so on in this patient population, and many of them do show benefits for that in kinds of end points, not the least in this study being hospitalization and emergency room avoidance. But I think the scalability and personnel issue is a huge one, and I do wonder at some level whether we may see some AI-based platforms coming along that could actually help with this and provide interactions with these patients outside of actual real people, or at least in combination with real people. Dr. Hamilton: Yeah, that's a fantastic point.  So let's talk a little bit about clinical trials. So eligibility assessment for oncology clinical trials, or prescreening, really relies on manual review of unstructured clinical notes. It's time-consuming, it's prone to errors, and Abstract 1508 reported on the final analysis of a randomized trial that looked at the effect of human-AI teams prescreening for clinical trial eligibility versus human-only or AI-only prescreening. So give us more good news about AI. What did the study find? Dr. Sweetenham: Yeah, this is a really, a really interesting study. And of course, any of us who have ever been involved in clinical trials will know that accrual is always a problem. And I think most centers have attempted, and some quite successfully managed to develop prescreening programs so that patients are screened by a health care provider or health care worker prior to being seen in the clinic, and the clinical investigator will then already know whether they're going to be eligible for a trial or not. But as you've already said, it's a slow process. It's typically somewhat inefficient and requires a lot of time on the part of the health care workers to actually do this in a successful way. And so, this was a study from Emory University where they took three models of ways in which they could assess the accuracy of the prescreening of charts for patients who are going to be considered for clinical trials. One of these was essentially the regular way of having two research coordinators physically abstract the charts. The second one was an AI platform which would extract longitudinal EHR data. And then the third one was a combination of the two. So the AI would be augmented by the research coordinator or the other way around. As a gold standard, they had three independent oncology reviewers who went through all of these charts to provide what they regarded as being the benchmark for accuracy. In a way, it's not a surprise to me because I think that a number of other systems which have used this combination of human verification of AI-based tools, it actually ultimately concluded that the combination of the two in terms of chart accuracy was for the most part better than either one individually, either the research coordinator or the AI alone. So I'll give you just a few examples of where specifically that mattered. The human plus AI platform was more accurate in terms of tumor staging, in terms of identifying biomarker testing and biomarker results, as well as biomarker interpretation, and was also superior in terms of listing medications. There are one or two other areas where either the AI alone was somewhat more accurate, but the significant differences were very much in favor of a combination of human + AI screening of these patient charts. So, in full disclosure, this didn't save time, but what the authors reported was that there were definite efficiency gains, and presumably this would actually become even more improved once the research coordinators were somewhat more comfortable and at home with the AI tool. So, I thought it was an interesting way of trying to enhance clinical trial accrual up front by this combination of humans and technology, and I think it's going to be interesting to see if this gets adopted at other centers in the future. Dr. Hamilton: Yeah, I think it's really fascinating, all the different places that we can be using AI, and I love the takeaway that AI and humans together are better than either individually. Dr. Sweetenham: Absolutely.  Thanks once again, Dr. Hamilton, for sharing your insights with us today and for all of the incredible work you did to build a robust program. And also, congratulations on what was, I think, a really remarkable ASCO this year, one of the most exciting for some time, I think. So thank you again for that. Dr. Hamilton: Thanks so much. It was really a pleasure to work on ASCO 2025 this year. Dr. Sweetenham: And thank you to our listeners for joining us today. You'll find links to all the abstracts we discussed today in the transcript of this episode. Be sure to catch up on all of our coverage from the Annual Meeting. You can catch up on my daily reports that were published each day of the Annual Meeting, featuring the key science and innovations presented. And we'll have wrap-up episodes publishing in June, covering the full spectrum of malignancies from ASCO25. If you value the insights you hear on the ASCO Daily News Podcast, please remember 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.   More on today's speakers: Dr. John Sweetenham   Dr. Erika Hamilton @erikahamilton9   Follow ASCO on social media:  @ASCO on Twitter  ASCO on Bluesky  ASCO on Facebook   ASCO on LinkedIn     Disclosures:     Dr. John Sweetenham:     No relationships to disclose    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

In our 17th season of the Marrow Masters podcast, we will be focusing on Adolescents and Young Adults, collectively known as AYAs.  Defined as between the ages of 15 and 39 by the National Cancer Institute, these patients have a unique cancer journey.  They are often too old for pediatric clinics, but feel out of place among older adults in a tradtional oncology department.This season we will talk to survivors, social workers, caregivers, and doctors.  And you won't want to miss a conversation between two moms who have become family - when one made a life saving donation to the other's daughter.Thanks to our Season 17 Sponsors:Leukemia and Lymphoma Society (LLS): https://lls.org/and Incyte: https://incyte.com/ National Bone Marrow Transplant Link - (800) LINK-BMT, or (800) 546-5268.nbmtLINK Website: https://www.nbmtlink.org/nbmtLINK Facebook Page: https://www.facebook.com/nbmtLINKFollow the nbmtLINK on Instagram! https://www.instagram.com/nbmtlink/The nbmtLINK YouTube Page can be found by clicking here.To participate in the GVHD Mosaic, click here: https://amp.livemosaics.com/gvhd

This week's episode is incredibly close to my heart, and not the usual type of episode I share since this is largely a story about me. Just a few months after becoming a nurse, I was diagnosed with a rare bone marrow disorder known as a myeloproliferative neoplasm (MPN). Since then, I've shared bits of that journey here and there, but today, I'm going deeper with a very special guest: Becca Claassen, an oncology nurse with InCyte and a fellow MPN warrior. Together, Becca and I explore what it's like to live with an MPN and what nurses need to know to better care for patients with this chronic condition. Whether you've never heard of MPNs or you care for oncology patients regularly, this episode offers a powerful blend of clinical insight and personal experience. In this episode, you'll learn: What an MPN (myeloproliferative neoplasm) is and why it's so complex Common types of MPNs and how they affect the body Symptoms patients may experience How to be a more empathetic and informed nurse when caring for someone with a rare chronic illness Our personal stories of diagnosis, treatment, and day-to-day life with an MPN This isn't just a clinical overview. It's a conversation between two nurses who are also patients. I hope it helps you walk away with a better understanding of what your patients might be going through, both physically and emotionally. __________________________ ⁠Voices of MPN Mobile Tracker App⁠ - Share this tool with your MPN patients so they can track their symptoms and have more meaningful conversations with their care team.

The Lymphoma Hub was pleased to speak to Grzegorz S. Nowakowski, Mayo Clinic, Rochester, US, who discussed the real-world experience of tafasitamab and lenalidomide for the treatment of relapsed/refractory diffuse large B-cell lymphoma. This educational resource is independently supported by Incyte. All content is developed by SES in collaboration with an expert steering committee; funders are allowed no influence on the content of this resource. Hosted on Acast. See acast.com/privacy for more information.

This educational resource is independently supported by Incyte. All content is developed by SES in collaboration with an expert steering committee; funders are allowed no influence on the content of this resource. Gilles Salles, Memorial Sloan Kettering Cancer Center, New York, US, discusses the evolving treatment landscape for relapsed/refractory diffuse large B-cell lymphoma, focusing on the combination of tafasitamab and lenalidomide. He highlights how this immunotherapy regimen, targeting CD19, has shown promising efficacy, with a high overall response rate and sustained complete responses in some patients. Salles also addresses real-world data, the regimen's tolerability, and its positioning in the treatment sequence, particularly for patients who are not candidates for CAR T-cell therapy. Lastly, he emphasizes the importance of tailoring treatment strategies based on patient characteristics and emerging therapies. Hosted on Acast. See acast.com/privacy for more information.

Dr. John Sweetenham and Dr. Erika Hamilton discuss top abstracts that will be presented at the 2025 ASCO Annual Meeting, including research on tech innovations that could shape the future of oncology. Transcript Dr. John Sweetenham: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. John Sweetenham, and I'm delighted to be joined today by Dr. Erika Hamilton, a medical oncologist and director of breast cancer and gynecologic cancer research at the Sarah Cannon Research Institute in Nashville, Tennessee. Dr. Hamilton is also the chair of the 2025 ASCO Annual Meeting Scientific Program, and she's here to tell us about some of the key abstracts, hot topics, and novel approaches in cancer care that will be featured at this year's Annual Meeting. Our full disclosures are available in the transcript of this episode. Dr. Hamilton, it's great to have you on the podcast today, and thanks so much for being here. Dr. Erika Hamilton: Thanks, Dr. Sweetenham. I'm glad to be here. Dr. John Sweetenham: Dr. Hamilton, the Presidential Theme of the Annual Meeting this year is ‘Driving Knowledge to Action: Building a Better Future,' and that's reflected in many of the sessions that will focus on action-oriented guidance to improve care for our patients. And as always, there'll be great presentations on practice-changing abstracts that will change treatment paradigms and transform care. Can you tell us about some of the hot topics this year and what you're particularly excited about? Dr. Erika Hamilton: You're right. Dr. Robin Zon's theme is ‘Driving Knowledge to Action: Building a Better Future,' and you're going to see that theme really interlaced throughout the ASCO program this year. We had a record number of submissions. Over 5,000 abstracts will be published, and there'll be about 3,000 presentations, either in oral format or poster presentations. We have 200 dynamic sessions. Many of the discussants will be highlighting key takeaways and how we can translate action-oriented guidance to better treat our patients to build a better future. Our state-of-the-art science will include a Plenary Session. This will feature presentations as well as discussion of each of the presentations for clinical late-breaking abstracts. We have Clinical Science Symposia that I'm particularly excited about this year. These will feature key abstracts as well as discussions and a foundational talk around the subject. We're covering novel antibody-drug conjugate targets, turning “cold” tumors “hot” to include CAR T, as well as the future of cancer detection. There'll be rapid oral abstracts, case-based panels, and this will also feature interactive audience polling and case discussions. I also want to highlight the community connection opportunities. There will be 13 Communities of Practice that will be meeting on-site during ASCO, and there's also really a plethora of networking opportunities for trainees and early-career professionals, a Women's Networking Center, a patient advocate space, and I'm happy to report there will also be live music out on the terrace this year at ASCO. Dr. John Sweetenham: Well, that's going to be a really great addition. I have to say, I think this is always a special time of year because excitement starts to mount as the meeting gets closer and closer. And once the abstracts are out there, I certainly personally feel that the excitement builds. Talking of abstracts, let's dive into some of the key abstracts for this year's meeting. I'd like to start out by asking you about Abstract 505. This reports on 15-year outcomes for women with premenopausal hormone receptor-positive early breast cancer in the SOFT and TEXT trials. It assesses the benefits of adjuvant exemestane and ovarian function suppression or tamoxifen and ovarian function suppression. So, could you talk us through this and tell us what you think the key takeaways from this abstract are? Dr. Erika Hamilton: Absolutely. This is essentially the SOFT and TEXT trials. They are trials that we've been following for quite some time, evidenced by the 15-year outcome. And I think it really answers two very important questions for us regarding adjuvant endocrine therapy for patients that are facing hormone receptor-positive disease. The benefit of ovarian function suppression for one, and then second, the benefit of exemestane over tamoxifen, which is our SERM [selective estrogen receptor modulator]. So, in terms of the SOFT trial, when we talk about distance recurrence-free interval, which I really think is probably the most meaningful because secondary cancers, et cetera, are not really what we're getting at here. But in terms of distant recurrence-free interval, certainly with tamoxifen, using tamoxifen plus ovarian function suppression adds a little bit. But where we really get additional benefits are by moving to exemestane, an aromatase inhibitor with the ovarian function suppression. So, for example, in SOFT, for distant recurrence-free interval for patients that have received prior chemotherapy, the distance recurrence-free interval was 73.5% with tamoxifen, bumped up just a tiny bit to 73.8% with ovarian function suppression. But when we used both ovarian function suppression and switched to that aromatase inhibitor, we're now talking about 77.6%. It may seem like these are small numbers, but when we talk about an absolute benefit of 4%, these are the type of decisions that we decide whether to offer chemotherapy based on. So, really just optimizing endocrine therapy really can provide additional benefits for these patients. Just briefly, when we turn to TEXT, similarly, when we look at distance recurrence-free interval for our patients that are at highest risk and receive chemotherapy, tamoxifen and ovarian function suppression, 79%; 81% with exemestane and ovarian function suppression. And when we talk about our patients that did not receive chemotherapy, it increased from 91.6% up to 94.6%—very similar that 3% to 4% number. So, I think that this is just very important information when counseling our patients about the decisions that they're going to make for themselves in the adjuvant setting and how much we want to optimize endocrine therapy. Dr. John Sweetenham: Thanks so much for your insight into that. Dr. Erika Hamilton: Yeah, absolutely. So, let's turn to hematologic malignancies. Abstract 6506 reports exciting results on the new agent ziftomenib in relapsed/refractory NPM1-mutant acute myeloid leukemia. This is a phase 1b clinical activity study and safety results. This was the pivotal KOMET-001 study. And my question is, will this new agent fulfill an unmet need in this NPM1 space? Dr. John Sweetenham: Yeah, great question. And I think the answer is almost certainly ‘yes'. So, just as some brief background, NPM1 mutation is known to be a driver of leukemogenesis in around 30% of patients with AML, and it's a poor prognostic factor. And typically, about 50% of these patients will relapse within a year of their first-line therapy, and only around 10% of them will get a subsequent complete remission with salvage therapy. Menin inhibitors, which disrupt the interaction between menin and KMT2A, are known to be active in NPM1-mutated as well as in KMT2A-rearranged AML. And ziftomenib is a selective oral menin inhibitor, which in this study was evaluated at a dose of 600 mg once a day, as you mentioned, a phase 1b/2 study, which is multicenter and presented by Dr. Eunice Wang from Roswell Park. It's a relatively large study of 112 patients who were treated with this standard dose with relatively short median follow-up at this time. The median age was 69 years, and median prior therapies were two, but with a range of one to seven. And I think very importantly, 60% of these patients had previously been treated with venetoclax, and 23% of them had had a prior transplant. Looking at the results overall for this study, the overall response rate was 35%, which is actually quite impressive. Specifically for those patients in the phase 2 part of the study, around 23% achieved a CR [complete remission] or CRh [complete remission with partial hematologic recovery]. What's very interesting in my mind is that the response rates were comparable in venetoclax-naive and venetoclax-exposed patients. And the drug was very well tolerated, with only 3% of patients having to discontinue because of treatment-related adverse events. And I think the authors appropriately conclude that, first of all, the phase 2 primary endpoint in the study was met, and that ziftomenib achieved deep and durable responses in relapsed and refractory NPM1-mutated AML, regardless of prior venetoclax, with good tolerance of the drug. And so, I think putting all of this together, undoubtedly, these data do support the potential use of this agent as monotherapy and as a new option for those patients who have relapsed or refractory NPM1-mutated acute myeloid leukemia. So, let's move on a little bit more now and change the subject and change gears completely and talk about circulating tumor DNA [ctDNA]. This has been a hot topic over a number of years now, and at this year's meeting, there are quite a few impactful studies on the use of ctDNA. We have time to focus on just one of these, and I wanted to get your thoughts on Abstract 4503. This is from the NIAGARA trial, which looks at ctDNA in patients with muscle-invasive bladder cancer who receive perioperative durvalumab. Could you tell us a little bit about this study? Dr. Erika Hamilton: So, this was the phase 3 NIAGARA trial, and this is literally looking for patients with muscle-invasive bladder cancer that are cisplatin-eligible, and the addition of durvalumab to neoadjuvant chemotherapy. So here, this is a planned exploratory analysis of ctDNA and the association with clinical outcomes from NIAGARA. So, this is really the type of study that helps us determine which of our patients are more likely to have a good outcome and which of our patients are more likely not to. There were 1,000 randomized patients in this study, and 462 comprised the biomarker-evaluable population. There were about half in the control arm and half in the durvalumab arm. And overall, the ctDNA-positive rate at baseline was about 57%, or a little over half, and that had decreased to about 22% after neoadjuvant treatment. ctDNA clearance rates from baseline to pre-radical cystectomy was about 41% among those with durvalumab and 31% among those in control. And the non-pCR rate was 97% among patients with pre-cystectomy ctDNA-positive status. So, this really gives us some information about predicting who is going to have better outcomes here. We did see a disease-free survival benefit with perioperative durvalumab, and this was observed in post-cystectomy ctDNA-positive as well as the ctDNA-negative groups. Shifting gears now to GI cancer, Abstract 3506 is a long-term safety and efficacy study of sotorasib plus panitumumab and FOLFIRI for previously treated KRAS G12C-mutated metastatic colorectal cancer. And this is the CodeBreaK-101 study. What are your thoughts on this study? Dr. John Sweetenham: Yeah, thanks. A very interesting study, and this abstract builds upon the phase 3 CodeBreaK-300 trial, which I think has just been published in the Journal of Clinical Oncology. This showed that the combination of sotorasib and panitumumab improved clinical outcomes in patients with chemorefractory KRAS G12C-mutated metastatic colorectal cancer. The current abstract, as you mentioned, reports the CodeBreaK-101 trial. And this was a phase 1b trial where FOLFIRI therapy was added to sotorasib and panitumumab in previously treated patients with KRAS G12C-mutated metastatic colorectal cancer. The abstract reports the overall and progression-free survival results, as well as some updated safety and response data. So, in this study, patients with this particular mutation who had received at least one prior systemic treatment but were KRAS G12C inhibitor-naive were enrolled into an expansion cohort of the CodeBreaK-101 protocol. And these patients received what apparently now recommended as the standard phase 2 dose of sotorasib of 960 mg daily, plus panitumumab and a standard dose of FOLFIRI. And the primary endpoint of the study was safety, and secondary endpoints included confirmed response, overall response, and progression-free survival, as assessed by the investigator. And by November of last year, 40 patients had been enrolled into this study. Common treatment-related adverse events were cutaneous; some patients developed neutropenia, and stomatitis was fairly widespread. Discontinuation of sotorasib because of adverse events was only seen in 1% of patients, although patients did have to discontinue because of toxicity from some of the other agents in the combination. Looking at the results of this study, the updated objective response rate was 57.5%, and the disease control rate was estimated at 92%, going on 93%, with a median time to response of 1.6 months and a median response duration of 6 months. After a median follow-up of 29.2 months, the median progression-free survival was 8.2 months, and the overall survival 17.9 months. So, the authors have concluded that this combination, including sotorasib, panitumumab, and FOLFIRI, does appear to show quite promising long-term efficacy in pretreated patients with this specific mutation. The ongoing phase 3 study they mentioned, CodeBreaK-301, is aiming to evaluate this combination against the standard of care in the first-line setting for patients with KRAS G12C-mutated colorectal cancer. So, promising results, and we'd be very interested to see how this particular combination performs in the frontline. Dr. Erika Hamilton: Fantastic. Thanks so much for sharing that. Let's shift gears again and really talk about digital technology. I feel that we're all going to have to get much better with this, and really, there are a lot of promises for our patients coming here. There are a lot of abstracts at ASCO that are focusing on innovations in digital technology, including a really interesting psychosocial digital application for caregivers of patients that are undergoing hematopoietic stem cell transplantation. Can you tell us a little bit about this? It's Abstract 11000. Dr. John Sweetenham: Yeah, absolutely. This abstract certainly caught my eye, and I think it's intriguing for a number of reasons, partly because it's app-based, and partly also because it specifically addresses caregiver burden and caregiver needs in the oncology setting, which I think is especially important. And although the context, the clinical context of this study, is hematopoietic stem cell transplantation, I think it has potential applications way beyond that. We all know that caregivers of patients undergoing stem cell transplantation have significant quality-of-life struggles. They are well-documented to have significant psychological and emotional strain before, during, and after stem cell transplantation. And this abstract describes an application called BMT-CARE, which is aimed at improving caregivers' quality of life, caregiver burden, mood symptoms, and coping skills, and so on. So, this was a single-center, randomized trial from MGH [Massachusetts General Hospital] of this app for stem cell transplant caregivers, compared with usual care in those individuals. And the eligible patients, or eligible individuals, were adults caring for patients with heme malignancy undergoing either an autologous or an allogeneic stem cell transplant. Patients were randomly assigned either to use the app or for usual care. And the app itself—and I think it'll be interesting to actually see this at the meeting and visualize it and see how user-friendly and so on it is—but it comprises five modules, which integrate psychoeducation, behavior change, stress management, and they're delivered through a kind of interactive platform of educational games and videos. And then participants were self-reporting at baseline and then 60 days after transplant. So, around 125 patients were enrolled in this study, of around 174 who were initially approached. So, just over 70% uptake from caregivers, which is, I think, relatively high, and evenly distributed between the two randomized arms. And the majority of the participants were spouses. And at 60 days post-stem cell transplant, the intervention participants reported a better quality of life compared with those who received usual care. If you break this down a little bit more, these participants reported lower caregiving burden, lower incidence of depression, fewer PTSD symptoms, and overall better coping skills. So, the authors conclude that this particular app, a digital health intervention, led to pretty substantial improvements in quality of life for these caregivers. So, intriguing. As I said, it'll be particularly interesting to see how this thing looks during the meeting. But if these kind of results can be reproduced, I think this sort of application has potential uses way beyond the stem cell transplant setting. Dr. Erika Hamilton: Yeah, I find that just so fascinating and very needed. I think that the caregiving role is often underestimated in how important that is for the patient and the whole family, and really giving our caregivers more tools in their toolbox certainly is quite helpful. Dr. John Sweetenham: Absolutely. Well, the meeting is getting closer, and as I mentioned earlier, I think anticipation is mounting. And I wanted to say thanks so much to you for chatting with me today about some of the interesting advances in oncology that we're going to see at this year's meeting. There is a great deal more to come. Our listeners can access links to the studies we've discussed today in the transcript of this episode. I'm also looking forward, Dr. Hamilton, to having you back on the podcast after the Annual Meeting to dive into some of the late-breaking abstracts and some of the other key science that's captured the headlines this year. So, thanks once again for joining me today. Dr. Erika Hamilton: Thanks so much for having me. Pleasure. Dr. John Sweetenham: And thank you to our listeners for joining us today. Be sure to catch my “Top Takeaways from ASCO25.” These are short episodes that will drop each day of the meeting at 5:30 p.m. Eastern Time. So, subscribe to the ASCO Daily News Podcast wherever you prefer to listen, and join me for concise analyses of the meeting's key abstracts.   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.   More on today's speakers: Dr. John Sweetenham   Dr. Erika Hamilton @erikahamilton9   Follow ASCO on social media:  @ASCO on Twitter  ASCO on Bluesky  ASCO on Facebook   ASCO on LinkedIn     Disclosures:     Dr. John Sweetenham:     No relationships to disclose  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

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.Regeneron has acquired ownership of 23andme for $256 million, promising to comply with consumer privacy policies. Makary's proposed rare disease pathway has sparked hope but raised questions among experts. At the American Society of Gene and Cell Therapy meeting, the first personalized in vivo CRISPR therapy was reported. The FDA has cleared the first Alzheimer's blood test, potentially boosting uptake of Alzheimer's disease therapies. Bio-Rad's new Center for Excellence is redefining antibody discovery with their Pioneer Antibody Discovery Platform. FDA regulations are unlikely to save money for the industry, and Applied Therapeutics' rare disease treatment has failed in late-stage trials. The memory gap in forgotten diseases is making a dangerous comeback, and Novo CEO's sudden exit has raised concerns among analysts.FDA Commissioner Marty Makary's proposal for a 'conditional approval' pathway for rare diseases has sparked hope among biopharma companies, but experts are raising concerns about safety, access, and liability due to a lack of details. The FDA and NIH are accelerating the shift away from animal research, which has raised questions about safety and implementation. Meanwhile, FDA cuts have led to chaos in planning for upcoming advisory committee meetings. The Trump administration's efforts to slash regulations may not necessarily benefit the industry as anticipated. Sarepta is seeking to strengthen its case for Elevidys with data in older kids, while other companies such as Incyte and Lilly are making progress with their drug approvals. Overall, the biopharma industry is facing challenges and uncertainties in navigating the evolving regulatory landscape.

This episode of PedsCases will give you an approach to congenital hemangiomas. By the end of this podcast, listeners will be able to 1) define hemangiomas and congenital hemangiomas, 2) explain the genetics and environmental factors associated with congenital hemangiomas, 3) describe the pathogenesis of congenital hemangiomas, 4) classify congenital hemangiomas, and 5) discuss the diagnosis, differential diagnosis, and management strategies for congenital hemangiomas. Today's episode was created by Emilie Wang, a medical student at the University of British Columbia, in collaboration with Dr. Joseph Lam, a pediatric dermatologist at BC Children's Hospital. An author of this podcast has financial support and has received speaker bursaries from Johnson & Johnson, Pierre-Fabre, Pfizer, Valeant, Sanofi Genzyme, Incyte, La Roche Posay Canada, Beiersdorf Canada and serves on advisory committees for Johnson & Johnson, Pierre-Fabre, Pfizer, Valeant, Sanofi Genzyme. They also serve as Associate Editor of Pediatric Dermatology Journal, and have been contributors to UpToDate, Medscape, BMJ Updates, and Eczema Society of Canada.  

Incyte Corporation v. Sun Pharmaceutical Industries, Ltd.

During the 66th American Society of Hematology (ASH) Meeting and Exposition, the Lymphoma Hub was pleased to speak to Stefano Luminari, University of Modena and Reggio Emilia, Modena, IT. We asked about the latest updates from the inMIND trial of tafasitamab plus lenalidomide and rituximab for R/R FL. In this interview, Luminari shares data from the phase III inMIND (NCT04680052) trial of patients with relapsed/refractory follicular lymphoma treated with tafasitamab in combination with lenalidomide and rituximab. Luminari covers key outcomes, highlighting promising efficacy and safety data. He concludes that the data are encouraging and supports using this combination for patients with relapsed/refractory follicular lymphoma in the second-line setting.This educational resource is independently supported by Incyte. All content is developed by SES in collaboration with an expert steering committee; funders are allowed no influence on the content of this resource. Hosted on Acast. See acast.com/privacy for more information.

Audio roundup of selected biopharma industry content from Scrip over the business week ended 21 March 2025. In this episode: Pfizer tops pharma leaderboard; AstraZeneca buys into in vivo cell therapy; Almirall looks to dominate derma spectrum; Incyte's HS contender looks approvable; and MSD's Williams says pharma should shorten tech adoption cycles. https://insights.citeline.com/scrip/podcasts/scrips-five-must-know-things/quick-listen-scrips-five-must-know-things-EGD3MLOIVJDKRCE32KV376CJ5Q/ This episode was produced with the help of AI text-to-voice and voice emulation tools. Playlist: soundcloud.com/citelinesounds/sets/scrips-five-must-know-things

Miramos a valores como el Índice manufacturero Empire State de marzo, Incyte, RBC Capital, DuPont, FedEx, Nike y GE AEROSPACE. Con Ignacio Vacchiano, responsable de distribución en España de Leverage Shares.

Wenn es um Medikamente geht, habt ihr als Patientinnen und Patienten mehr Rechte als ihr denkt. Oftmals lohnt es sich beim Arzt nachzufragen, um ein neueres Medikament oder einen besser passenden Wirkstoff zu bekommen. Und wie sieht es eigentlich mit Medikamenten aus, die noch gar nicht zugelassen sind - können sie zum Beispiel bei lebensbedrohlichen Erkrankungen trotzdem eingesetzt werden? Darüber sprechen wir mit Bibiane Schulte-Bosse, Fachanwältin für Medizinrecht. Sie erklärt, warum Mediziner Erkrankungen wie die Weißfleckenkrankheit Vitiligo manchmal fälschlicherweise als Lifestyle-Erkrankung einstufen und sich nicht trauen Medikamente zu verordnen, obwohl das möglich wäre und wie Patienten dann am besten vorgehen. Außerdem klären wir, was ihr tun könnt, wenn ihr den Verdacht habt, dass euer Arzt einen Behandlungsfehler gemacht hat.

Join Prof. Lisa Beck as she explores the chronic and persistent burden of AD as well as the concept of early intervention.   ADVENT is a medical education non-promotional resource for healthcare professionals organized by Sanofi and Regeneron. Learn more at ADVENTprogram.com.   This podcast is intended for healthcare professionals only.   Disclaimer: This program is non-promotional and is sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. The speakers are being compensated and/or receiving an honorarium from Sanofi and Regeneron in connection with this program. The content contained in this program was jointly developed by the speakers and Sanofi and Regeneron and is not eligible for continuing medical education (CME) credits.   Speaker disclosures: Lisa Beck MD, consults for Abbvie, Allakos, Arcutis Biotherapeutics, Arena Pharmaceuticals, Aslan Pharma, Astria Therapeutics, Celldex, Dermavent, DermTech, Escient Pharma, Eli Lilly Company, Evelo Biosciences, Galderma, Incyte, Janssen, LEO Pharma, Merck, Nektar Therapeutics, Numab Therapeutics, Pfizer, Proteologix, Rapt Therapeutics, Regeneron, Ribon Therapeutics, Sanofi/Genzyme, Sanofi-Aventis, Sitryx Therapeutics, Stealth BioTherapeutics, Trevi Therapeutics, Union Therapeutics, Xencor and Yuhan and has been an Investigator for Abbvie, Astra-Zeneca, DermTech, Kiniksa, Pfizer, Regeneron, Ribon Therapeutics and Sanofi.    © 2025 Sanofi and Regeneron Pharmaceuticals, Inc. All Rights Reserved. MAT-GLB-2407353  – 1.0 – 02/2025 MAT-US-2501683 v1.0 - P Expiration Date: 02/24/2027

On this episode of Biotech Hangout, Eric Schmidt, Bruce Booth, Yaron Werber, Tim Opler and Mike Yee begin the show discussing the highlights from the Jefferies Healthcare Conference before taking a look at public investor sentiment this week. The discussion turns to Atlas Venture's 2024 Year in Review and transitions into the emerging themes for 2025. The hosts also recap ACR Convergence including Amgen's Phase 3 data as well as data from cell therapies for SLE, SSC, IMNM. The group also discuss lipid readouts from Eli Lilly, Silence Therapeutics and NewAmsterdam Pharma. Other topics covered include the Incyte and Escient deal collapse, Kura Oncology's pact with Kyowa Kirin, and perspectives on Trump's nomination of Dr. Mehmet Oz to lead the CMS. This episode aired on November 22, 2024.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world.Private equity firms Blackstone and Bain Capital are close to finalizing a potential $3 billion deal for Mitsubishi's pharma unit, Mitsubishi Tanabe Pharma. In other news, five drugs have been flagged for unjustified price hikes in 2023 by the Institute for Clinical and Economic Review. Incyte and Iteos are cutting drug candidates from their cancer pipelines due to disappointing data, while the FDA advisory committee has called for more research on Moderna's RSV vaccine after safety issues arose. Layoffs have been announced at Intercept and Editas, and there has been a slowdown in M&A activity in the pharma industry this year. US Pharmacopeia is looking for expert volunteers to work on medicine quality challenges.

This 30-minute CME-accredited program, hosted by John Kuruvilla, MD, discusses best practices for talking to patients with hematologic malignancies about possibly participating in clinical trials.Jointly Provided by American Academy of CME and CheckRare CE.Support for this accredited continuing education activity has been made possible through educational grant from Merck.Estimated time to complete: 0.5 hours Start date: November 30, 2024End date: November 30, 2025  Activity FacultyJohn Kuruvilla, MDHematologist / Clinical InvestigatorPrincess Margaret Cancer CentreProfessor of MedicineUniversity of Toronto Target AudienceThis activity has been designed to meet the educational needs of physicians specializing in hematology-oncology. Other healthcare providers, including NPs and PAs, may also participate. Learning ObjectivesAfter participating in the activity, learners should be better able to- Describe the importance of clinical trials in furthering the science of hematologic malignancies treatment.- Describe and utilize best practices for engaging patients in shared decision making regarding clinical trial participation. Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. 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. PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.5 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation. Disclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.Disclosure of relevant financial relationships are as follows: Faculty Educator/PlannerDr. Kuruvilla discloses the following relevant financial relationships with ineligible companies:Honoraria: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Beigene, Genmab, Gilead Sciences, GlaxoSmithKline, Incyte, Janssen, Karyopharm, Merck, Novartis, Pfizer, Roche, Seattle GeneticsConsultant: AbbVie, Bristol Myers Squibb, Gilead Sciences/Kite, Merck, Roche, Seattle GeneticsGrant/Research Support: AstraZeneca, Kite, Merck, Novartis, RocheData Safety Monitoring Board: KaryopharmPlanners for this activity have no relevant financial relationships with any ineligible companies. This activity will not review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information. Method of ParticipationThere are no fees to participate in the activity. Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please go to https://checkrare.com/learning/p-hematologic-malignancies-and-clinical-trial-participation-a-shared-decision-making-approach/   PrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ContactFor any questions, please contact: CEServices@academycme.org               

Dr. Linda Duska and Dr. Domenica Lorusso discuss the practice-changing results of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, which evaluated pembrolizumab plus chemoradiotherapy as treatment for previously untreated, high-risk, locally advanced cervical cancer. TRANSCRIPT  Dr. Linda Duska: Hello, I'm Linda Duska, your guest host of the ASCO Daily News Podcast today. I'm a professor of obstetrics and gynecology and serve as the associate dean for clinical research at the University of Virginia School of Medicine. On today's episode, we'll be discussing a new standard of care for previously untreated, high- risk locally advanced cervical cancer. This follows the ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, which I will be referring to as KEYNOTE-A18 for the rest of this podcast, which demonstrated that pembrolizumab plus chemoradiotherapy improved both progression-free and overall survival compared to chemoradiotherapy alone. I was a co-author of this study, and I'm delighted to be joined today by the study's lead investigator, Dr. Domenica Lorusso, for today's discussion. She is also a professor of obstetrics and gynecology. She's at Humanitas University Rosano and the director of the Gynecologic Oncology Unit at the Humanitas Hospital San Pio in Milan, Italy. Our full disclosures are available in the transcript of this episode. Dr. Lorusso, it's great to be speaking with you today. Dr. Domenica Lorusso: Thank you, Linda. It's a great pleasure to be here. Thank you. Dr. Linda Duska: So I was hoping you could start us out with some context on the challenges associated with treating patients with high-risk, locally advanced cervical cancer. Dr. Domenica Lorusso: Yes. I have to make a disclosure because in my experience as a gynecologist, cervical cancer patients are the most difficult patients to treat. This is a tumor that involves young patients [who often have] small kids. This is a very symptomatic tumor. More than 50% of patients report pain. Sometimes the pain is difficult to control because there is an infiltration of the pelvic nerves and also a kind of vaginal discharge, so it's very difficult to treat the tumor. Since more than 25 years, we have the publication of 5 randomized trials that demonstrate that when we combine platinum chemotherapy to radiation treatment, we increase overall survival by 6%. This is the new standard of care – concurrent chemoradiation plus brachytherapy. This is a good standard of care because particularly modern, image-guided radiotherapy has reported to increase local control. And local control in cervical cancer translates to better overall survival. So modern radiotherapy actually is able to cure about 75% of patients. This is what we expect with chemoradiation right now. Dr. Linda Duska: So what are the key takeaways of A18? This is a really exciting trial, and you've presented it a couple of times. Tell us what are the key takeaways that you want our listeners to know. Dr. Domenica Lorusso: Linda, this is our trial. This is a trial that we did together. And you gave me the inspiration because you were running a randomized phase 2 trial exploring if the combination of pembrolizumab to concurrent chemoradiation was able to give signals of efficacy, but also was feasible in terms of toxicity. There were several clinical data suggesting that when we combine immunotherapy to radiotherapy, we can potentially increase the benefit of radiotherapy because there is a kind of synergistic effect between the two strategies. Radiotherapy works as a primer and immunotherapy works better. And you demonstrated that it was feasible to combine immunotherapy to concurrent chemoradiation. And KEYNOTE-A18 was based on this preliminary data. We randomized about 1,060 patients to receive concurrent chemoradiation and brachytherapy or concurrent chemoradiation and brachytherapy in combination with pembrolizumab followed by pembrolizumab for about two years. Why two years? Because in more than 80% of cases, recurrence in this patient population occurred during the first two years. So the duration of treatment was based on the idea to provide protection to the patient during the maximum time of risk. And the trial had the two primary endpoints, progression free and overall survival, and met both the endpoints, a significant 30% reduction in the risk of progression that was confirmed. At the 3-year follow up, the observation was even better, 0.68. So 32% reduction in the risk of progression. And more importantly, because this is a curative setting, 33% reduction in the risk of death was reported in the experimental arm when pembro was combined with chemoradiation. Dr. Linda Duska: That's amazing. I wanted to ask you, a prior similar study called CALLA was negative. Why do you think A18 was positive? Dr. Domenica Lorusso: Linda, there are several discussions about that. I had the possibility to discuss several times with the PI of CALLA, Brad Monk. The idea of Brad is that CALLA was negative because of using durvalumab instead of PD-1 inhibitor, which is pembrolizumab. I do not have exactly the same impression. My idea is that it's the kind of patient population enrolled. The patient population enrolled in KEYNOTE-A18 was really a high-risk population; 85% of that patient were node positive, where the definition of node positivity was at least 2 lymph nodes in the pelvis with a short diameter of 1.5. So, we are very confident this patient was node-positive, 55% at the grade 3 and 4 diseases. So this is really a high-risk population. I remember at the first presentation of CALLA, I was honored to discuss the CALLA trial when it was first presented at IGCS a few years ago. And when I received the forest plot of Calla, it was evident to me that in patients with stage III and node positive there was a signal of efficacy. And we have a huge number of patients with node positive. So in my opinion this is the reason why KEYNOTE-A18 is positive. Dr. Linda Duska: Yeah, I agree with you. I've thought about it a lot and I think you're right about that. The INTERLACE trial results were recently published. How should we interpret these results in the context of A18? Dr. Domenica Lorusso: So it's very difficult to compare the 2 trials. First of all, in terms of population. The population enrolled in INTERLACE is a low-risk, locally advanced but low risk population; 76% were stage II, 10% were stage I, 60% were node-negative patients. So, first of all, the population is completely different. Second is the type of radiotherapy that was provided. INTERLACE is a 10-year long trial, but in 10 years the quality and the technique of radiotherapy completely changed. Only 30% of patients in INTERLACE received what we call the modern image-guided brachytherapy, which is important because it provides local control and local control increases overall survival. And third, we read the paper. I'm not a methodologist, but there are some methodological biases in the paper. All the statistical design of the trial was based on PFS, but PFS was evaluated at physician description. And honestly, I never saw a trial that had no pre-specified timeline for radiological evaluation. It's very difficult to evaluate progression in cervical cancer because the fibrosis related to radiotherapy changes the anatomy in the pelvis. And I think that the radiological evaluation is important to address if the patient is progressing or not. Particularly, because the conclusion of CALLA is that the PFS was mainly in favor of distant metastasis. So really, it's difficult for me to understand how distant metastasis may be evaluated with the vagina visit. So really, it's very difficult to compare the two trials, but I have some concerns. And also because of toxicity in the study, unfortunately 30% of patients did not complete concurrent chemoradiation because of residual toxicity due to induction chemotherapy. So I wanted to be sure in the context of modern radiotherapy, if really induction chemo adds something to modern radiotherapy. Dr. Linda Duska: Well, I have two more questions for you. As we move immunotherapy into the front line, at least for these high risk locally advanced cervical cancer patients that were eligible for A18, what does that mean then for hopefully those few that develop recurrence in terms of second line therapy? Dr. Domenica Lorusso: Well, Linda, this is a very important question. We do not have data about immuno after immuno, but I would not completely exclude this hypothesis because in KEYNOTE-A18, the patient received treatment for a well-defined time period. And for those patients not progressing during immunotherapy, I really guess if there is a space for the reintroduction of immunotherapy at the time of recurrence. In this moment we have 30% of patients in KEYNOTE-A18 in the control arm that receive immunotherapy after progression, but still we have 11% of patients that receive immunotherapy in combination with concurrent chemoradiation and then receive, again, immunotherapy in later line of therapy. I think we need to collect these data to capture some signals and for sure we have the new drug. We have antibody drug conjugate. The trials are ongoing exploring the role of antibody drug conjugate, particularly in immune pretreated patients. So I think this is a very interesting strategy. Dr. Linda Duska: I was going to ask you, “What are the next steps,” but I think you already answered that question. You talked about the second line. If you were going to redesign a study in the frontline, what would it look like? Dr. Domenica Lorusso: Probably one question that I would like to answer – there are two questions in my opinion in KEYNOTE-A18 – one is induction immunotherapy. Linda, correct me if I'm wrong, you reported very interesting data about the immune landscape change when you use induction immunotherapy. And I think this is something that we need to explore in the future. And the second question is the duration of maintenance. Because, again, we decided for two years based only on the epidemiology of recurrence, but I guess if one year may be enough. Dr. Linda Duska: I think this sequencing question is really important, that the induction immunotherapy was actually GY017. I can't take credit for that, but I think you're right. I think the sequencing question is really important. Whether you need the concurrent IO or not is an important question. And then to your point about the 2 years, the length of the need for maintenance therapy is a question that we don't know the answer to. So there are lots of really important questions we can continue to ask. I want to thank you so much for sharing your valuable insights with us on the podcast today. You're always so thoughtful about this particular study and cervix cancer in general and also for your great work to advance the care for patients with GYN cancers. Dr. Domenica Lorusso: Thank you, Linda. It's our work - we progress together. Dr. Linda Duska: Yes. And we thank the patients as well. The over 1,000 patients that went on this trial during a pandemic. Right? Dr. Domenica Lorusso: Absolutely. Without their generosity and their trust, we would not be able to do this trial. Dr. Linda Duska: So we're very grateful to them and we thank 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. Thank you all.   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. Linda Duska @Lduska Dr. Domenica Lorusso   Follow ASCO on social media:   @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn     Disclosures:   Dr. Linda Duska: Consulting or Advisory Role: Regeneron, Inovio Pharmaceuticals, Merck, Ellipses Pharma Research Funding (Inst.): GlaxoSmithKline, Millenium, Bristol-Myers Squibb, Aeterna Zentaris, Novartis, Abbvie, Tesaro, Cerulean Pharma, Aduro Biotech, Advaxis, Ludwig Institute for Cancer Research, Leap Therapeutics Patents, Royalties, Other Intellectual Property: UptToDate, Editor, British Journal of Ob/Gyn Dr. Domenica Lorusso: Consulting or Advisory Role: PharmaMar, AstraZeneca, Clovis Oncology, GSK, MSD, Genmab, Seagen, Immunogen, Oncoinvest, Corcept, Sutro Biopharma, Novartis, Novocure, Daiichi Sankyo/Lilly Speakers' Bureau: AstraZeneca, Clovis, GSK, MSD, ImmunoGen, Seagen Research Funding (Inst.): PharmMar, Clovis, GSK, MSD, AstraZeneca, Clovis Oncology, Genmab, Seagen, Immunogen, Incyte, Roche, Pharma&, Corcept Therapeutics, Alkermes Travel, Accommodations, Expenses: AstraZeneca, Clovis, GSK, Menarini  

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

This podcast will discuss an approach to morphea. The podcast was created by Amir Pourghadiri, a fourth-year medical student at the University of British Columbia, Jeffrey Toy, a dermatology resident at the University of British Columbia, and Dr. Joseph Lam, a pediatric dermatologist at the BC Children's Hospital. An author of this podcast has financial support from Johnson & Johnson, serves on an advisory board for Galderma, Johnson & Johnson Inc, Pfizer, Pierre-Fabre, Sanofi Genzyme, Valeant, Health Plexus, and Incyte, and also received a speaker bursary from Johnson & Johnson Inc. Pierre-Fabre, Pfizer, Valeant, La Roche Posay, and Beiersdorf.

Peds derm discussions with Dr. Lisa Swanson! - Infant gut microbiota and risk for allergic disease - Maternal vitamin D and atopic dermatitis - Tocilizumab for H syndrome - Nadolol = or > propranolol for hemangiomas Lisa Swanson can be found at lisaswansonmd@gmail.com Want to donate to the cause? Do so here!Donate to the podcast: uofuhealth.org/dermasphereCheck out our video content on YouTube:www.youtube.com/@dermaspherepodcastand VuMedi!: www.vumedi.com/channel/dermasphere/The University of Utah's DermatologyECHO: ⁠physicians.utah.edu/echo/dermatology-primarycare -⁠ Connect with us!- Web: ⁠dermaspherepodcast.com/⁠ - X: @DermaspherePC- Instagram: dermaspherepodcast- Facebook: www.facebook.com/DermaspherePodcast/- Check out Luke and Michelle's other podcast,SkinCast! ⁠healthcare.utah.edu/dermatology/skincast/⁠Dermasphere has received an unrestricted educational grant from Incyte Corporation. Thanks, Incyte!Check out our friends at:- ⁠Kikoxp.com ⁠(a social platform for doctors to share knowledge)- ⁠www.levelex.com/games/top-derm⁠ (A free dermatology game to learnmore dermatology!

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world.Evotec is exiting the gene therapy field and cutting jobs due to a slowdown in research spending. Merck has made a $700 million bet on an antibody drug for immune diseases, while Lilly has opened a new R&D hub in Boston. Ovid and Lexicon have laid off staff, and Merck's TIGIT drug has failed another trial. Intellia's therapy for hereditary angioedema has succeeded in a study. The gene therapy market is growing, particularly in cancer care, with companies continuing to invest in improving cell therapies. Cabaletta Bio's shares have sunk on safety concerns, while Vertex has secured reimbursement for Casgev in England. The world's priciest drug may save lives, but there are concerns about whether children can access it in time. Overall, the gene therapy industry is experiencing various developments and challenges as companies navigate the evolving landscape.The Biden administration announced that negotiated drug prices through the IRA program are expected to save Medicare $6 billion in 2026, although the actual savings may not be as significant as claimed. Gilead's investment in CymaBay paid off with FDA approval for a drug to treat autoimmune liver disease. Evotec is the latest biopharma company to announce layoffs in August. In other news, Incyte received a second FDA approval for a drug to treat graft-versus-host disease, while bluebird is experiencing slow uptake of its gene therapies for sickle cell and beta-thalassemia. The role of quality assurance and regulatory affairs (QARA) professionals is evolving, with strategies and best practices being discussed. Various marketing campaigns and strategies are being discussed, including Lobos 1707 casting LeBron James as a spy in new ads, Martha Stewart playing an intern in a Fiverr campaign, and US Bank celebrating black achievement with zines in The New York Times. Additionally, Allbirds' CMO talks about the importance of brand building in the company's turnaround plan. The text also includes information about first-party data strategies, an upcoming webinar on the state of marketing and print projects in 2024, and other relevant industry news and resources.In the healthcare industry, Medicare revealed the results of drug price negotiations, which are expected to save taxpayers $6 billion. Kaiser Permanente has implemented an AI documentation tool from Abridge to summarize medical information from patient-clinician conversations. Meanwhile, Medicaid has surpassed Medicare Advantage as a challenge for health insurers in the second quarter, but many still reported significant earnings. In other news, there are updates on healthcare worker strikes and unsealed court filings detailing a Department of Justice investigation into Prospect Medical for possible false claim act violations.The text discusses the health disparities highlighted by the COVID-19 pandemic, particularly among minority groups, and how these disparities were exacerbated during the crisis. It also explores the importance of building trust among patients of color in the healthcare system despite historical injustices and ongoing disparities. Dr. Reed Tuckson, a leader in public health outreach to people of color, shares lessons learned from the pandemic and discusses how pharma can better serve these communities.The U.S. government has unveiled the prices it will pay for 10 widely used medicines as part of its efforts to lower prescription drug costs through Medicare negotiations. These prices will not take effect until 2026, but the announcement marks a significant step in a process established by the Inflation Reduction Act. Biopharma Dive provides detailed coverage of this development and other industry news, offering insight into topics such as clinical readouts, FDA approvals, gene therapy, druSupport the Show.

Dr. Sonja Ständer and Dr. Shawn Kwatra discuss the unique characteristics of prurigo nodularis (PN) and its clinical definition and explore how some of these characteristics are shared with atopic dermatitis, including underlying type 2 inflammation. They also discuss the need to raise awareness of this disease among both physicians and patients and educate that this is not a psychodermatological disorder. ADVENT is a medical education non-promotional resource for healthcare professionals organized by Sanofi and Regeneron. Learn more at ADVENTprogram.com. This podcast is intended for healthcare professionals only. Disclaimer:  This program is non-promotional and is sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. The speakers are being compensated and/or receiving an honorarium from Sanofi and Regeneron in connection with this program The content contained in this program was jointly developed by the speakers and Sanofi and Regeneron and is not eligible for continuing medical education (CME) credits Speaker disclosures: Dr. Shawn Kwatra is an advisory board member/consultant for Abbvie, Amgen, Arcutis Biotherapeutics, Aslan Pharmaceuticals, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Dermavant, Galderma, Incyte Corporation, Johnson & Johnson, Leo Pharma, Novartis Pharmaceuticals Corporation, Pfizer, Regeneron Pharmaceuticals, and Sanofi and has served as an investigator for Galderma, Incyte, Pfizer, and Sanofi. Dr. Sonja Ständer was speaker and/or consultant and/or Investigator and/or has received research funding from AbbVie, Almirall, Beiersdorf, BMS, Clexio, Eli Lilly, FomF, Galderma, German Research Foundation (DFG), Integrity CE, Kiniksa, Leo Pharma, L'Oréal, MEDahead, Moroscience, NACCME, Novartis, Omnicuris, P.G. Unna Academy, Pfizer, Sanofi, TouchIME, UCB, Vifor, and WebMD. © 2024 Sanofi and Regeneron Pharmaceuticals, Inc. All Rights Reserved. MAT-GLB-2400085- 1.0 - 08/2024 MAT-US-2408113 v1.0-P Expiration Date: 08/13/2026

Join Drs. April Armstrong and Lisa Beck for a conversation around the long-term burden and effects of AD. They will discuss the underlying pathophysiology of AD and how early intervention may impact disease course. ADVENT is a medical education non-promotional resource for healthcare professionals organized by Sanofi and Regeneron. Learn more at ADVENTprogram.com. This podcast is intended for healthcare professionals only. Disclaimer:  This program is non-promotional and is sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. The speakers are being compensated and/or receiving an honorarium from Sanofi and Regeneron in connection with this program The content contained in this program was jointly developed by the speakers and Sanofi and Regeneron and is not eligible for continuing medical education (CME) credits Speaker disclosures: April Armstrong, MD, MPH has served as a research investigator, scientific advisor, or speaker to AbbVie, Amgen, Almirall, Arcutis, ASLAN, Beiersdorf, BI, BMS, EPI, Incyte, Leo, UCB, Janssen, Lilly, Mindera, Nimbus, Novartis, Ortho, Sun, Dermavant, Dermira, Sanofi, Takeda, Organon, Regeneron, Pfizer and Ventyx Lisa Beck MD, consults for Abbvie, Allakos, Arcutis Biotherapeutics, Arena Pharmaceuticals, Aslan Pharma, Astria Therapeutics, Celldex, Dermavent, DermTech, Escient Pharma, Eli Lilly Company, Evelo Biosciences, Galderma, Incyte, Janssen, LEO Pharma, Merck, Nektar Therapeutics, Numab Therapeutics, Pfizer, Proteologix, Rapt Therapeutics, Regeneron, Ribon Therapeutics, Sanofi/Genzyme, Sanofi-Aventis, Sitryx Therapeutics, Stealth BioTherapeutics, Trevi Therapeutics, Union Therapeutics, Xencor and Yuhan and has been an Investigator for Abbvie, Astra-Zeneca, DermTech, Kiniksa, Pfizer, Regeneron, Ribon Therapeutics and Sanofi.  © 2024 Sanofi and Regeneron Pharmaceuticals, Inc. All Rights Reserved. MAT-GLB-2401395 - 1.0 - 07/2024 MAT-US-2407636 v1.0 - P Exp Date: 07/31/2026

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

In today's podcast, we have the pleasure of speaking with Angie Giallourakis, a dedicated advocate and founder of the Steven G. Cancer Foundation and Elephants and Tea. Angie shares her powerful story of being a caregiver to her son Steven, who battled cancer twice. Steven was first diagnosed with stage four osteosarcoma in 2006, and later with secondary acute myelogenous leukemia (AML) in 2008, necessitating a bone marrow transplant.Angie recounts the emotional and physical toll of Steven's journey, describing the intense periods of treatment and the unexpected challenges they faced. After his bone marrow transplant, Steven experienced graft-versus-host disease (GVHD). Angie shares vivid anecdotes, including a harrowing moment when Steven's salivary glands swelled, causing his face to balloon. This incident, among others, highlights the unpredictable nature of GVHD and the constant vigilance required from caregivers.Angie emphasizes the importance of stress management for caregivers. She advocates for finding personal ways to cope, whether through exercise, yoga, meditation, or prayer. Her own methods include Yoga Nidra, a type of meditation, and seeking solace in prayer. She also stresses the importance of good nutrition and staying hydrated, which can be challenging during long hospital stays.Drawing from her experiences, Angie advises caregivers to seek help when needed and to communicate openly with their loved ones and medical teams. She underscores the necessity of validating the patient's pain and symptoms, as Steven's experience with inflammation throughout his body was initially dismissed by some as psychological.The conversation shifts to Angie's founding of the Steven G. Cancer Foundation. Motivated by the outdated treatments Steven received, she aimed to raise awareness and fund research for adolescent and young adult (AYA) cancer. She also talks about Elephants and Tea, a magazine by and for cancer patients, founded with her son Nick. The magazine provides a platform for unfiltered stories from cancer patients and has expanded to include workshops, community support, and therapeutic resources.Angie's message to new caregivers is clear: understand the potential challenges, communicate effectively, and don't hesitate to ask for and accept help. She highlights the importance of social support, both for patients and caregivers, to navigate the emotional and physical demands of cancer treatment.As we wrap up, Angie encourages listeners to reach out to organizations, consume available resources, and connect with others in similar situations. Her final words resonate with a message of hope and validation: you are not alone in this journey.More:Steven G. Cancer Foundation: https://www.stevengcancerfoundation.orgElephants and Tea: https://www.elephantsandtea.comNational Bone Marrow Transplant Link - (800) LINK-BMT, or (800) 546-5268.nbmtLINK Website: https://www.nbmtlink.org/nbmtLINK Facebook Page:  https://www.facebook.com/nbmtLINKnbmtLINK YouTube Page can be found by clicking here.This season is made possible thanks to donations from Syndax and Incyte.https://syndax.com/https://incyte.com/ Follow the nbmtLINK on Instagram! https://www.instagram.com/nbmtlink/

Dr. Doris Ponce from Memorial Sloan Kettering Cancer Center delves into atypical presentations of chronic graft-versus-host disease (cGVHD). As an associate member, co-chair of the Center for Hematologic Malignancies, and director of the Graft-Versus-Host Disease Program, Dr. Ponce provides an in-depth understanding of this complex condition.Dr. Ponce emphasizes the diverse symptoms of GVHD that often overlap with other conditions, making diagnosis challenging. She outlines the eight organs typically affected by GVHD: skin, mouth, eyes, musculoskeletal, genitourinary, lungs, liver, and gastrointestinal tract. However, she highlights that GVHD can also present atypically in organs such as the kidneys, nervous system, muscles, heart, and pancreas, causing symptoms such as serositis, effusions, nephrotic syndrome, and autoimmune disorders like vitiligo.Atypical presentations of GVHD are rare and require exclusion of other conditions such as drug side effects or infections before diagnosis. Dr. Ponce stresses the importance of patients communicating any new or unusual symptoms with their clinicians, as these might not initially seem connected to GVHD.Focusing on skin-related GVHD, Dr. Ponce describes common and atypical manifestations, including tight skin (sclerodermatous changes), pigmentation loss, dryness, and psoriasis-like appearances. Treatment varies but often involves topical steroids or immune suppression tailored to individual symptoms. For daily skincare, she advises avoiding frequent hot showers, using lukewarm water, and selecting gentle, fragrance-free products to prevent skin irritation.Regarding sun exposure, Dr. Ponce recommends using broad-spectrum sunscreen with SPF 30 or higher, and wearing protective clothing to prevent rashes exacerbated by sunlight. She also discusses the use of chemical and mineral sunscreens, noting that mineral sunscreens, despite being thicker, are better suited for sensitive skin.Peggy and Dr. Ponce discuss the Long Good Feel Better program that the American Cancer Society provides. For patients wanting to wear makeup, Dr. Ponce suggests choosing products designed for sensitive skin, avoiding those with harsh ingredients or multiple components, and replacing makeup regularly to prevent contamination. She also warns against using organic or preservative-free makeup due to infection risks.Haircare after GVHD often involves managing hair loss and changes in texture. Dr. Ponce advises infrequent washing, using gentle products, and considering supplements like biotin. For wigs, she cautions against those requiring glue and suggests alternatives like clip-on wigs or scarves. Hair dyeing is permissible with ammonia-free products.Nail care post-transplant includes using nail hardeners and avoiding acrylic nails. Dr. Ponce also emphasizes checking for underlying issues like vitamin deficiencies that may affect nail health.In closing, Dr. Ponce highlights the holistic approach to patient care at Memorial Sloan Kettering Cancer Center, addressing both medical and psychological aspects to support patients' overall well-being. She encourages patients to communicate any concerns, as seemingly minor symptoms might significantly impact their health and recovery. Dr. Ponce's dedication to improving patients' lives extends beyond treating their conditions, fostering confidence and quality of life throughout their recovery journey.More:Memorial Sloan Kettering Cancer Center's Tips for Managing GVHD (created by Dr. Ponce and dermatologist) Dr. Alina Markova:https://www.mskcc.org/cancer-care/patient-education/tips-managing-graft-versus-host-disease-gvhdAmerican Cancer Society's Look Good Feel Better Program: https://lookgoodfeelbetter.org/Memorial Sloan Kettering Cancer Center Website: https://www.mskcc.org/Sally Hansen Nail Hardener: https://www.sallyhansen.com/en-us/nail-care/nail-care/mega-strength-hardenerSurvivor recommended clothing brands that have SPF/UPF clothing:Coolibar: https://www.coolibar.com/Columbia: https://www.columbia.com/c/sun-protection/Baleaf: https://www.baleaf.com/collections/upf50This season is made possible thanks to donations from Syndax and Incyte.https://syndax.com/https://incyte.com/ Follow the nbmtLINK on Instagram! https://www.instagram.com/nbmtlink/

This epsiode includes content related to reproductive organs and sexual health and may not be suitable for all listeners.In this podcast, we welcome Dr. Jose Flores, an expert in sexual and reproductive medicine at New York's Memorial Sloan Kettering Cancer Center. We dive deep into the often challenging but crucial topic of male sexuality, particularly in the context of cancer treatment and graft versus host disease (GVHD).Dr. Flores begins by distinguishing between sexual dysfunction and erectile dysfunction (ED). He emphasizes that sexual dysfunction encompasses various issues beyond just achieving erections, such as ejaculation problems, orgasm issues, decreased sex drive, and changes in penile shape. This broader understanding is essential when discussing sexual health with patients.The prevalence of ED after cancer treatment is notably high, with up to 60-70% of men experiencing it post-chemotherapy, and even higher rates following pelvic surgery, specifically. Low testosterone levels also contribute significantly to sexual dysfunction, particularly after treatments targeting the pelvic area.A critical aspect of addressing ED is breaking the wall of silence around it. Dr. Flores stresses the importance of open communication between patients and healthcare providers. Initiating conversations about sexual health can lead to better assessments and treatments. He outlines the initial steps in diagnosing ED, including patient questionnaires and lab tests, and underscores the need for healthcare providers to proactively ask patients about their sexual health.The discussion then shifts to the impact of GVHD on sexual function. Dr. Flores notes that about 70% of men post-bone marrow or stem cell transplant suffer from low testosterone and ED. Unfortunately, without intervention, these issues do not typically resolve on their own. Patients must seek help to explore treatment options.Dr. Flores explains the ED treatment model, which follows a stepwise approach. The first step includes lifestyle modifications and the use of PDE-5 inhibitors like Viagra and Cialis. If these are ineffective, injection therapy is the next step, followed by mechanical aids like penile pumps and, as a last resort, penile implants.Myths and realities of PDE-5 inhibitors are addressed, clarifying that these medications require proper usage, including an empty stomach for Viagra and sufficient time for absorption for Cialis, along with sexual stimulation to be effective. Proper education on these aspects can significantly enhance their effectiveness.Low testosterone, particularly after cancer treatment, is another major topic. Dr. Flores discusses the complexities of testosterone replacement therapy (TRT), including potential risks like polycythemia, effects on fertility, and the necessity of screening for conditions like sleep apnea and prostate cancer before starting treatment. He advises patients to preserve fertility before undergoing cancer treatments and outlines options for those with compromised fertility post-treatment.The conversation concludes with Dr. Flores urging patients to be proactive about their sexual and reproductive health. He highlights the importance of seeking specialized care and the positive impact it can have on overall quality of life. Throughout the discussion, Dr. Flores's compassionate approach underscores the importance of addressing these sensitive issues openly and effectively.Memorial Sloan Kettering Cancer Center: https://www.mskcc.orgInternational Index of Erectile Dysfunction: https://www.uptodate.comTestosterone Replacement Therapy Information: https://www.urologyhealth.orgThis season is made possible thanks to donations from Syndax and Incyte.https://syndax.com/https://incyte.com/ Follow the nbmtLINK on Instagram! https://www.instagram.com/nbmtlink/

In this episode, we speak with Brigham and Women's Hospital and Dana Farber Cancer Institute's Dr. Hermioni "Hermi" Amonoo, an esteemed psychiatrist, psychosocial oncologist, and associate professor at Harvard Medical School. Our discussion centers on the psychological distress associated with graft versus host disease (GVHD) following a bone marrow stem cell transplant. Dr. Amonoo sheds light on the significant psychological challenges patients with GVHD face, noting that approximately 50% experience clinically significant depression, and about a third suffer from anxiety. This psychological distress permeates various aspects of daily life, affecting routines, relationships, and social roles.Dr. Amonoo uses a powerful analogy to describe psychological well-being, likening it to a toolbox filled with various tools and equipment essential for managing distress. Key components of this toolbox include psychotherapeutic interventions, health behaviors such as good nutrition and physical activity, medication when necessary, and professional help from specialty mental health clinicians. Social support and meaningful relationships also play a crucial role in enhancing wellbeing. Peer support, for instance, can offer valuable lived experiences and tips for thriving despite the challenges posed by GVHD.We also delve into the importance of the clinical team in managing cGVHD. The clinical team helps patients understand the disease, manage symptoms, and connect with resources. Dr. Amonoo emphasizes the importance of patients communicating openly with their clinical team, urging them not to hesitate in asking questions or expressing concerns about new symptoms.Pacing oneself is another critical aspect discussed. GVHD is not a static condition, and symptoms can evolve over time. Patients should give themselves grace, avoid overexertion, and maintain a sustainable pace to manage their energy levels effectively. Dr. Amonoo compares this to running a marathon, where pacing is essential to avoid burnout.Caregivers, who play a vital role in the patient's journey, must also prioritize their own well being. Dr. Amonoo stresses that caregiver well being directly impacts patient well being, encouraging caregivers to practice self-care and seek help when needed. Communication between caregivers and patients is crucial, especially as relationships and priorities may evolve during the recovery journey.As we conclude, Dr. Amonoo offers final advice to listeners: don't worry alone. Leverage your clinical team and support networks to navigate the challenges of recovery. This collaborative approach can significantly enhance the quality of life for both patients and caregivers.More:GVHD Upside Down Facebook Group: https://www.facebook.com/groups/gvhdupsidedownElephants and Tea: https://elephantsandtea.comNational Bone Marrow Transplant Link - (800) LINK-BMT, or (800) 546-5268.nbmtLINK Website: https://www.nbmtlink.org/nbmtLINK Facebook Page:  https://www.facebook.com/nbmtLINKnbmtLINK YouTube Page can be found by clicking here.This season is made possible thanks to donations from Syndax and Incyte.https://syndax.com/https://incyte.com/  Follow the nbmtLINK on Instagram! https://www.instagram.com/nbmtlink/

In this episode, we chat with JR Brandt of Montana, an acute lymphocytic leukemia (ALL) survivor, about his journey through diagnosis, treatment, and living with chronic graft-versus-host disease (cGVHD). JR shares his initial diagnosis story, describing how what he thought was a minor infection led to a leukemia diagnosis complicated by the Philadelphia Positive chromosome. He underwent 26 days of chemotherapy and was eventually cleared for a bone marrow stem cell transplant at Stanford University in March 2017.JR discusses the onset of chronic GVHD symptoms about a year after his transplant, beginning with skin changes. He was treated with Rituxan infusions, which provided temporary relief. Over the years, as symptoms re-emerged, JR continued Rituxan treatments and adjusted his care plan, even after moving from California to Montana. He highlights the importance of finding and continuing care with familiar healthcare professionals, like his physician who (fortunately) moved to Billings Clinic.Beyond skin issues, JR describes experiencing joint tightness, dry eyes, dysphagia, and dry mouth. He mentions practical solutions like using Biotene toothpaste for dry mouth and preservative-free Refresh Plus eyedrops for dry eyes. JR also shares the importance of physical and occupational therapy, which helped him develop a personalized exercise routine. Over time, he transitioned to aquatic aerobics and massage therapy, finding these methods more effective for managing his symptoms.JR emphasizes the significance of staying active, despite physical limitations, by adapting activities like biking with an e-bike and engaging in water aerobics. He also discusses the importance of sun protection and practical tips for managing GVHD symptoms, like using a sun hat and sunblock.JR addresses the mental health challenges of living with chronic illness, equating his experiences to PTSD and stressing the importance of setting goals and making plans to stay motivated. He shares how maintaining an active lifestyle and staying connected with his family helps him manage anxiety and stress.When discussing his career, JR explains how his background in healthcare was both a benefit and a challenge. He advises others with disabilities to utilize vocational rehabilitation services to explore new career paths. JR also encourages being your own patient advocate, ensuring all medical information is shared among healthcare providers to provide comprehensive care.JR concludes with the importance of using available resources, like the Americans with Disabilities Act, for mobility aids and other accommodations (link below). He highlights the need for continuous learning and resourcefulness in managing chronic GVHD and living life to the fullest. Products mentioned by JR in this episode:Refresh Eye Drops: https://www.refresheyedrops.com/Biotene for Dry Mouth: https://www.biotene.com/DaBrim Helmet/SunShade: https://dabrim.com/Oofos shoes: https://www.oofos.com/Mechanix Gloves: https://www.mechanix.com/Dycem Non-Slip tape: https://www.dycem-ns.com/Tryvaya (Prescription) Nasal Spray for Dry Eye: https://www.tyrvaya.com/Full list of Vocational Rehabilitation Agencies for all 50 states: https://rsa.ed.gov/about/statesAmericans With Disabilities Act (ADA) Requirements for Power-Driven Mobility Devices: https://www.ada.gov/resources/opdmds/This season is made possible thanks to donations from Syndax and Incyte.https://syndax.com/https://incyte.com/ Follow the nbmtLINK on Instagram! https://www.instagram.com/nbmtlink/

Season 14 of the Marrow Masters podcast produced by the National Bone Marrow Transplant Link will be out soon, focusing on the parts of chronic graft versus host disease we don't often talk about. We'll cover male and female sexuality, and atypical presentations of chronic GVHD. We'll share a patient and caregiver perspective related to chronic GVHD and take a deep dive into the psychosocial and emotional struggles of those with this rare and sometimes debilitating disease.Guests include Dr. Doris Ponce and Dr. Jose Flores Ramirez of Memorial Sloan Kettering Cancer Center in New York, Dr. Hermioni "Hermi" Amonoo of Dana Farber Cancer Institute in Boston, and Dr. Oluwatosin Goje of Cleveland Clinic. We also speak with JR Brandt of Montana, an inspiring ALL Survivor, and Angie Giallourakis, caregiver and founder of Elephants and Tea.Season 14 of the Marrow Masters podcast will offer survivors insight, compassion, and answers to infrequently discussed subjects. The Marrow Masters podcast is produced by the National Bone Marrow Transplant Link and sponsored this season by Incyte and Syndax. Look for all six episodes coming soon on Apple, Spotify, YouTube, or wherever you're listening right now.And for more, visit the National Bone Marrow Transplant Link at nbmtlink.org or follow the link below. Follow the nbmtLINK on Instagram! https://www.instagram.com/nbmtlink/

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.The biotech industry is experiencing significant growth, with drugmakers in the U.S. and Europe raising $6.8 billion in venture capital funding in the first three months of the year. This trendline explores the evolving biotech market and highlights hotspots of startup activity. Stories included focus on an unorthodox investment firm supporting biotech's 'infrastructure', the rise in private biotech funding, and insights from biotech landlord Alexandria on research clusters and the sector's recovery.A study presented at the Alzheimer's Association International Conference showed that Novo Nordisk's GLP-1 drug liraglutide may slow cognitive decline in Alzheimer's patients by 18% compared to placebo over one year of treatment. Additionally, Novo's diabetes drug Ozempic was found to be linked to a lower risk for tobacco use disorder. Pfizer and Merck reported strong second-quarter earnings exceeding Wall Street expectations. Novo Nordisk's Ozempic was also found to potentially help diabetics quit smoking according to new research. Other news includes AstraZeneca's Calquence achieving positive results in a Phase III trial for CLL and Ventyx ending development of a Tyk2 inhibitor after a Phase II flop in Crohn's disease.Pfizer has decided to quit its Duchenne gene therapy program, resulting in the termination of 150 staff members. Incyte has also trimmed its cancer drug pipeline by discontinuing the development of five experimental treatments. The biotech market is seeing an increase in M&A activity, with companies like Boehringer making deals to add to their cancer drug pipeline. Overall, the industry is evolving with a focus on efficiency, effectiveness, and ethical innovation in clinical research.Sanofi's recent record sales quarter for its immunology drug Dupixent has boosted the company's confidence in its long-term strategy, following a previous dip in share value due to growth target adjustments. The company's spinoff of its consumer unit Opella is part of a trend among big pharma companies to focus on biopharma futures. Sanofi's Dupixent, with an expanding list of indications, is showing long-term value for the company and has the potential to become one of the best-selling drugs in the world by the end of the decade.Cleveland Clinic has appointed its first Chief AI Officer, Ben Shahshahani, to lead the health system's AI strategy, focusing on managing safety, ethics, and data security concerns. Healthcare organizations are facing obstacles in increasing patient response rates through phone communication. Healthcare Dive provides insights and news for healthcare leaders, covering various topics such as health IT, policy & regulation, insurance, digital health, payer-provider partnerships, and value-based care.GSK has partnered with Flagship to help find new drugs and vaccines, similar to recent alliances with Pfizer and Novo Nordisk. Boehringer has acquired startup Nerio for up to $1.3 billion to expand its cancer drug pipeline. Autobahn raised $100 million for neuropsych drugs, while a startup led by former J&J executives, Third Arc Bio, raised $165 million for cancer and immune disease drugs. The competitive market for obesity drugs is growing, with analysts expecting significant revenue from drugs like Novo's and Eli Lilly's.Biopharma Dive provides in-depth coverage of industry news and trends, covering topics from clinical trials to drug pricing and research partnerships.Support the Show.

Donna, a retired speech-language pathologist and public-speaking teacher who has been living with polycythemia vera (PV), a rare, chronic blood cancer known as a myeloproliferative neoplasm (MPN), joins Peg Squier, M.D., Ph.D., Group Vice President, U.S. Medical Affairs at Incyte, to discuss Donna's journey with PV since diagnosis. Tune in as they share advice for patients who are looking for new options to help manage their MPN and the importance of being an advocate. This episode of The Mighty Podcast is sponsored by Incyte. Episode Transcript: https://bit.ly/3y3LQYO

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

Dr Linda Stein Gold and Dr Jonathan Silverberg discuss the epidemiology, clinical presentation, and classification of atopic dermatitis of the hand and feet as well the as quantifying the multidimensional burden it has on patients' quality of life in clinical practice. ADVENT is a medical education non-promotional resource for healthcare professionals organized by Sanofi and Regeneron. Learn more at ADVENTprogram.com. This podcast is intended for healthcare professionals only. Disclaimer:  This program is non-promotional and is sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. The speakers are being compensated and/or receiving an honorarium from Sanofi and Regeneron in connection with this program The content contained in this program was jointly developed by the speakers and Sanofi and Regeneron and is not eligible for continuing medical education (CME) credits Speaker disclosures: Dr Jonathan Silverberg: Honoraria as a consultant and/or advisory board member for AbbVie, Alamar, Aldena Therapeutics, Amgen, AOBiome, Apollo Pharma, Arcutis, Arena Pharmaceuticals, Asana, ASLAN Pharmaceuticals, Attovia, BiomX, Biosion, Bodewell, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, FIDE, Galderma, GSK, Incyte, Invea, Kiniksa, LEO Pharma, Lilly, Merck, MyOr Diagnostics, Nektar, Novartis, Optum, Pfizer, RAPT Therapeutics, Recludix, Regeneron, Sandoz, Sanofi-Genzyme, Shaperon, Target RWE, Teva, UNION, and UpToDate. Speaker for AbbVie, LEO Pharma, Lilly, Pfizer, Regeneron, and Sanofi-Genzyme. Institution received grants from Galderma, Incyte, and Pfizer. Dr Linda Stein Gold: Investigator/advisor and/or speaker for AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, Incyte, LEO Pharma, Pfizer, Regeneron, and Sanofi. © 2024 Sanofi and Regeneron Pharmaceuticals, Inc. All Rights Reserved. MAT-GLB-2400314 - 1.0 - 06/2024  MAT-US-2405589 v1.0 - P Exp Date: 06/04/2026

Dr Linda Stein Gold and Dr Jonathan Silverberg discuss the challenges associated with diagnosis of atopic dermatitis of the hands and feet and how disease severity can be assessed in clinical practice. ADVENT is a medical education non-promotional resource for healthcare professionals organized by Sanofi and Regeneron. Learn more at ADVENTprogram.com. This podcast is intended for healthcare professionals only. Disclaimer:  This program is non-promotional and is sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. The speakers are being compensated and/or receiving an honorarium from Sanofi and Regeneron in connection with this program The content contained in this program was jointly developed by the speakers and Sanofi and Regeneron and is not eligible for continuing medical education (CME) credits Speaker disclosures: Dr Jonathan Silverberg: Honoraria as a consultant and/or advisory board member for AbbVie, Alamar, Aldena Therapeutics, Amgen, AOBiome, Apollo Pharma, Arcutis, Arena Pharmaceuticals, Asana, ASLAN Pharmaceuticals, Attovia, BiomX, Biosion, Bodewell, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, FIDE, Galderma, GSK, Incyte, Invea, Kiniksa, LEO Pharma, Lilly, Merck, MyOr Diagnostics, Nektar, Novartis, Optum, Pfizer, RAPT Therapeutics, Recludix, Regeneron, Sandoz, Sanofi-Genzyme, Shaperon, Target RWE, Teva, UNION, and UpToDate. Speaker for AbbVie, LEO Pharma, Lilly, Pfizer, Regeneron, and Sanofi-Genzyme. Institution received grants from Galderma, Incyte, and Pfizer. Dr Linda Stein Gold: Investigator/advisor and/or speaker for AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, Incyte, LEO Pharma, Pfizer, Regeneron, and Sanofi. © 2024 Sanofi and Regeneron Pharmaceuticals, Inc. All Rights Reserved. MAT-GLB-2402602- 1.0 - 05/2024 MAT-US-2405594 v1.0 - P Exp Date: 06/04/2026

Corporate nonsense is once again dominating Delaware news, so we brought in Former State Representative John Kowalko to talk about Incyte and corporate incentives, the hospitals' fight against HB 350, and the new amendments to Delaware's corporate law. Show Notes:Massachusetts Millionaires TaxIncyte expansion and incentivesJordan Howell's two pieces on the corporate bill

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      

Looking for some optimism around HS treatments? We've got it here. This week, we're joined by Dr. Joslyn Kirby as she shares her experience in working with HS and talks the nuts and bolts of HS with diagnosis, pathogenesis, and novel treatment options coming down the pipeline. Each Thursday, join Dr. Raja and Dr. Hadar, board-certified dermatologists, as they share the latest evidence-based research in integrative dermatology. To learn more about HS and earn free CME credits, visit LearnSkin.com to enroll in the HS: Examining the Role of Immunology and Inflammation with Biologics and JAK Inhibition series.   Dr. Joslyn Kirby is a Professor of Dermatology at Penn State Hershey and Past President of the Hidradenitis Suppurativa Foundation. In clinic and through her research, she is focused on hidradenitis suppurativa, including its effects on people and outcome measurement.   Supported by independent educational grants from Incyte and UCB

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/SVX865. CME/MOC/AAPA credit will be available until March 7, 2025.Evolving Concepts in the Pathogenesis of Inflammatory Dermatologic Disorders and the Rationale for Targeted Biologic Therapy: Focus on Moderate to Severe Atopic Dermatitis, Prurigo Nodularis, Chronic Urticaria, and Bullous Pemphigoid 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 Sanofi and Regeneron Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerAdam Friedman, MD, FAAD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcutis Biotherapeutics, Inc.; Incyte; Janssen Pharmaceuticals, Inc.; and Regeneron Pharmaceuticals Inc./Sanofi.Grant/Research Support from Incyte and Janssen Pharmaceuticals, Inc.Speaker for Bristol Myers Squibb; Incyte; Janssen Pharmaceuticals, Inc.; and Regeneron Pharmaceuticals Inc./Sanofi.Co-Chair/PlannerShawn Kwatra, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; Arcutis Biotherapeutics, Inc.; Asian Pharmaceuticals Pvt. Ltd.; Bristol Myers Squibb; Cara Therapeutics; Castle Biosciences, Inc.; Celldex Therapeutics; Dermavant Sciences, Inc.; Galderma; Genzada Pharmaceuticals USA, Inc.; Incyte; Johnson & Johnson Services, Inc.; LEO Pharma A/S; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Sanofi.Grant/Research Support from Galderma; Incyte; Pfizer; and Sanofi.Co-Chair/PlannerPeter A. Lio, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Almirall, S.A.; Amyris, Inc.; AOBiome; ASLAN Pharmaceuticals Pte Ltd; Bristol Myers Squibb; Burt's Bees Products Company; Concerto Biosciences; Dermavant Sciences, Inc.; Galderma S.A.; Leo Pharma Inc.; Lilly; L'Oréal USA, Inc.; Merck & Co., Inc.; Micreos B.V.; MyOR; Pfizer; Pierre Fabre group; Regeneron Pharmaceuticals Inc./Sanofi Genzyme; Theraplex; UCB, Inc.; and Verrica Pharmaceuticals.Grant/Research Support from AbbVie Inc. and Regeneron Pharmaceuticals Inc./Sanofi Genzyme.Speakers Bureau participant with AbbVie Inc.; Galderma S.A.; Incyte; Leo Pharma Inc.; Lilly; L'Oréal USA, Inc.; Pfizer; and Regeneron Pharmaceuticals Inc./Sanofi Genzyme.Co-Chair/PlannerProfessor Dedee Murrell has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amryt Pharma plc; Castle Creek Biosciences, Inc.; Krystal Biotech; and RHEACELL GmbH & Co. KG.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.

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/SKH865. CME/MOC/AAPA/IPCE credit will be available until March 20, 2025.Making Precision Decisions in the Treatment of NSCLC With Common and Uncommon EGFR Mutations: How to Navigate the Expanding Options and Increasing Complexity 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 and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerJoshua Sabari, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Genentech, Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; Navire; Pfizer; Regeneron Pharmaceuticals Inc.; Sanofi Genzyme; and Takeda Pharmaceutical Company Limited.Grant/Research Support from Boehringer Ingelheim Pharmaceuticals, Inc.; Janssen Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; and Regeneron Pharmaceuticals Inc.Faculty/PlannerJyoti D. Patel, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AnHeart Therapeutics; AstraZeneca; Blueprint Medicines Corporation; Daiichi Sankyo, Inc.; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Sanofi; and Takeda Pharmaceutical Company Limited.Other Financial or Material Support for Travel from Daiichi Sankyo, Inc. and Tempus.Faculty/PlannerAlexander I. Spira, MD, PhD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; Array BioPharma Inc.; AstraZeneca/ MedImmune; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bristol Myers Squibb; Daiichi Sankyo, Inc./AstraZeneca; Incyte; Gritstone bio, Inc.; Janssen Research & Development; Jazz Pharmaceuticals, Inc.; Lily; Merck & Co., Inc.; Mersana Therapeutics; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; and Takeda Pharmaceutical Company Limited.Grant/Research Support from ADC Therapeutics SA; AbbVie Inc.; Alkermes; Amgen Inc.; Arch Therapeutics, Inc.; ArriVent Biopharma; Astellas Pharma US, Inc.; Astex Pharmaceuticals; AstraZeneca; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bluprint Oncology; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Gritstone bio, Inc.; Ignyta Inc; Incyte; Janssen Oncology; LAM Therapeutics, Inc.; Loxo Oncology; MacroGenics, Inc.; Medikine, Inc; MedImmune; Mersana Therapeutics; Mirati Therapeutics, Inc.; NALO Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Plexxikon; Regeneron Pharmaceuticals Inc.; Revolution Medicines, Inc.; Rubius Therapeutics; Scorpion Therapeutics; Synthekine; and Takeda Pharmaceutical Company Limited.Honoraria from Amgen Inc.; AstraZeneca/ MedImmune; Bayer; Bristol Myers Sqiubb; CytomX Therapeutics, Inc.; Janssen Pharmaceuticals, Inc.; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; and Takeda Pharmaceutical Company Limited.Stock Shareholder in Lilly.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.

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/SVX865. CME/MOC/AAPA credit will be available until March 7, 2025.Evolving Concepts in the Pathogenesis of Inflammatory Dermatologic Disorders and the Rationale for Targeted Biologic Therapy: Focus on Moderate to Severe Atopic Dermatitis, Prurigo Nodularis, Chronic Urticaria, and Bullous Pemphigoid 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 Sanofi and Regeneron Pharmaceuticals.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerAdam Friedman, MD, FAAD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Arcutis Biotherapeutics, Inc.; Incyte; Janssen Pharmaceuticals, Inc.; and Regeneron Pharmaceuticals Inc./Sanofi.Grant/Research Support from Incyte and Janssen Pharmaceuticals, Inc.Speaker for Bristol Myers Squibb; Incyte; Janssen Pharmaceuticals, Inc.; and Regeneron Pharmaceuticals Inc./Sanofi.Co-Chair/PlannerShawn Kwatra, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; Arcutis Biotherapeutics, Inc.; Asian Pharmaceuticals Pvt. Ltd.; Bristol Myers Squibb; Cara Therapeutics; Castle Biosciences, Inc.; Celldex Therapeutics; Dermavant Sciences, Inc.; Galderma; Genzada Pharmaceuticals USA, Inc.; Incyte; Johnson & Johnson Services, Inc.; LEO Pharma A/S; Novartis Pharmaceuticals Corporation; Pfizer; Regeneron Pharmaceuticals Inc.; and Sanofi.Grant/Research Support from Galderma; Incyte; Pfizer; and Sanofi.Co-Chair/PlannerPeter A. Lio, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Almirall, S.A.; Amyris, Inc.; AOBiome; ASLAN Pharmaceuticals Pte Ltd; Bristol Myers Squibb; Burt's Bees Products Company; Concerto Biosciences; Dermavant Sciences, Inc.; Galderma S.A.; Leo Pharma Inc.; Lilly; L'Oréal USA, Inc.; Merck & Co., Inc.; Micreos B.V.; MyOR; Pfizer; Pierre Fabre group; Regeneron Pharmaceuticals Inc./Sanofi Genzyme; Theraplex; UCB, Inc.; and Verrica Pharmaceuticals.Grant/Research Support from AbbVie Inc. and Regeneron Pharmaceuticals Inc./Sanofi Genzyme.Speakers Bureau participant with AbbVie Inc.; Galderma S.A.; Incyte; Leo Pharma Inc.; Lilly; L'Oréal USA, Inc.; Pfizer; and Regeneron Pharmaceuticals Inc./Sanofi Genzyme.Co-Chair/PlannerProfessor Dedee Murrell has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amryt Pharma plc; Castle Creek Biosciences, Inc.; Krystal Biotech; and RHEACELL GmbH & Co. KG.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.

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/SKH865. CME/MOC/AAPA/IPCE credit will be available until March 20, 2025.Making Precision Decisions in the Treatment of NSCLC With Common and Uncommon EGFR Mutations: How to Navigate the Expanding Options and Increasing Complexity 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 and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerJoshua Sabari, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Genentech, Inc.; Gilead Sciences, Inc.; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; Navire; Pfizer; Regeneron Pharmaceuticals Inc.; Sanofi Genzyme; and Takeda Pharmaceutical Company Limited.Grant/Research Support from Boehringer Ingelheim Pharmaceuticals, Inc.; Janssen Pharmaceuticals, Inc.; Mirati Therapeutics, Inc.; and Regeneron Pharmaceuticals Inc.Faculty/PlannerJyoti D. Patel, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AnHeart Therapeutics; AstraZeneca; Blueprint Medicines Corporation; Daiichi Sankyo, Inc.; Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Sanofi; and Takeda Pharmaceutical Company Limited.Other Financial or Material Support for Travel from Daiichi Sankyo, Inc. and Tempus.Faculty/PlannerAlexander I. Spira, MD, PhD, FACP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Amgen Inc.; Array BioPharma Inc.; AstraZeneca/ MedImmune; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bristol Myers Squibb; Daiichi Sankyo, Inc./AstraZeneca; Incyte; Gritstone bio, Inc.; Janssen Research & Development; Jazz Pharmaceuticals, Inc.; Lily; Merck & Co., Inc.; Mersana Therapeutics; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; and Takeda Pharmaceutical Company Limited.Grant/Research Support from ADC Therapeutics SA; AbbVie Inc.; Alkermes; Amgen Inc.; Arch Therapeutics, Inc.; ArriVent Biopharma; Astellas Pharma US, Inc.; Astex Pharmaceuticals; AstraZeneca; Black Diamond Therapeutics; Blueprint Medicines Corporation; Bluprint Oncology; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; CytomX Therapeutics, Inc.; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche Ltd; Gritstone bio, Inc.; Ignyta Inc; Incyte; Janssen Oncology; LAM Therapeutics, Inc.; Loxo Oncology; MacroGenics, Inc.; Medikine, Inc; MedImmune; Mersana Therapeutics; Mirati Therapeutics, Inc.; NALO Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Plexxikon; Regeneron Pharmaceuticals Inc.; Revolution Medicines, Inc.; Rubius Therapeutics; Scorpion Therapeutics; Synthekine; and Takeda Pharmaceutical Company Limited.Honoraria from Amgen Inc.; AstraZeneca/ MedImmune; Bayer; Bristol Myers Sqiubb; CytomX Therapeutics, Inc.; Janssen Pharmaceuticals, Inc.; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; and Takeda Pharmaceutical Company Limited.Stock Shareholder in Lilly.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.

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/AAPA information, and to apply for credit, please visit us at PeerView.com/RGD865. CME/AAPA credit will be available until February 28, 2025.Leveraging TROP2 Expression in NSCLC: Expert Perspectives on the Present Evidence and Future Potential of TROP2-Targeting ADCs in Lung Cancer 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 an educational grant from Daiichi Sankyo, 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.; Genentech, Inc./F. Hoffmann-La Roche Ltd.; Guardant Health; Janssen Pharmaceuticals, Inc.; Lilly; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; and Pfizer.Faculty/PlannerCharu Aggarwal, MD, MPH, FASCO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca; BeiGene; Blueprint Genetics; Boehringer Ingelheim Pharmaceuticals, Inc.; Celgene Corporation; Daiichi Sankyo/AstraZeneca; Eisai; Genentech, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck and Co., Inc.; Pfizer; Regeneron Pharmaceuticals Inc./Sanofi; Shionogi Inc.; and Turning Point Therapeutics, Inc.Grant/Research Support from AstraZeneca/MedImmune; Genentech, Inc./F. Hoffmann-La Roche Ltd; Incyte; Macrogenics, Inc; and Merck Sharpe and Dohme LLC.Faculty/PlannerProf. Solange Peters, MD, PhD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; Arcus Biosciences; AstraZeneca; Bayer AG; BeiGene; BerGenBio; Biocartis; BioInvent; Blueprint Medicines; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Clovis Oncology; Daiichi Sankyo Co., Ltd.; Debiopharm International SA; ecancer; Elsevier; F. Hoffmann-La Roche/Genentech; F-star Therapeutics Inc.; Fishawack Health Group; Foundation Medicine, Inc.; Genzyme; Gilead Sciences Inc.; GlaxoSmithKline: HUTCHMED; Illumina, Inc.; Incyte Corporation; Ipsen Biopharmaceuticals, Inc.; IQVIA Inc.; iTeos Therapeutics; Janssen Global Services, LLC; Lilly; Merck Serono; Merck Sharp and Dohme Corp.; Merrimack; Mirati Therapeutics, Ind.; Novartis; Novocure; Pfizer; PharmaMar AG; Promontory Therapeutics; Regeneron Pharmaceuticals Inc.; Sanofi; Seattle Genetics; Takeda Pharmaceutical Company Limited; and Vaccibody. All fees to institution.Grant/Research Support from (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen Inc.; AstraZeneca; Biodesix, Inc.; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; Clovis Oncology; F. Hoffmann-La Roche/Genentech; GlaxoSmithKline; Illumina, Inc.; Lilly; Merck Serono; Merck Sharp and Dohme Corp.; Mirati Therapeutics, Inc.; Novartis; Pfizer; and Phosplatin Therapeutics.Other Financial or Material Support for talks in a company's organized public event from AstraZeneca; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb; ecancer; F. Hoffmann-La Roche/Genentech; Illumina, Inc.; Lilly; Merck Sharp and Dohme Corp.; Novartis; Pfizer; Sanofi; and Takeda Pharmaceutical Company Limited. All fees to institution. On the Board of Directors for Galencia SA.Faculty/PlannerJacob Sands, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Boehringer Ingelheim; Daiichi Sankyo, Inc.; Gilead Sciences, Inc.; Lilly; Medtronic; PharmaMar, and Sanofi.Grant/Research Support from Amgen Inc. and Harpoon Therapeutics.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.

Audio roundup of selected biopharma industry content from Scrip over the past business week. In this episode: optimistic outlook for biopharma IPOs; Boehringer's promising MASH results; Viking emerges as obesity contender; Incyte looks to portfolio diversification; and a look at China's HPV vaccine market. https://scrip.citeline.com/SC149879/Quick-Listen-Scrips-Five-MustKnow-Things

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.

Drs. Shaalan Beg and Rachna Shroff discuss key abstracts on GI cancers that were featured at the 2024 ASCO Gastrointestinal Cancers Symposium, including SKYSCRAPER-08, EMERALD-1, and NEST-1 in esophageal squamous cell carcinoma, hepatocellular carcinoma, and colorectal cancer, respectively. TRANSCRIPT Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host of the podcast today. I'm an adjunct associate professor at UT Southwestern's Simmons Comprehensive Cancer Center and vice president of oncology at Science 37. Today, we'll be discussing key abstracts and other exciting highlights from the 2024 ASCO Gastrointestinal Cancers Symposium. Joining me to discuss some key takeaways from the meeting is the chair of this year's Symposium, Dr. Rachna Shroff. Dr. Shroff is the division chief of Hematology Oncology and chief of GI Medical Oncology at the University of Arizona Cancer Center. She also serves as the associate dean for clinical and translational research at the University of Arizona College of Medicine – Tucson. 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.  Dr. Shroff, welcome back to the ASCO Daily News Podcast, and congratulations on a great Symposium. The scientific advances and innovative, multidisciplinary approaches that were featured throughout the meeting were really inspiring and reflect the incredible strides we're making in GI cancer research. Dr. Rachna Shroff: Thank you so much for having me back. I am delighted to be here.  Dr. Shaalan Beg: Dr. Shroff, the theme of this year's symposium was "Taking Personalized Care to the Next Level." I'd love to hear your reflections on the sessions that you found most exciting and really resonated with the attendees.  Dr. Rachna Shroff: Yes, thank you. We were really excited about this theme because we really felt that “Taking Personalized Care to the Next Level” translated to thinking through personalized approaches to patient care, not just in the traditional ways that we think of with precision oncology and genomics driving our care, but also how we can think through multidisciplinary approaches and an individualized care plan. Thinking through how artificial intelligence and novel clinical trial designs can and should be implemented to meet the needs of our individual patients. And so we really highlighted that in what was a somewhat new reboot of a session called “Intersections,” which were every day and were really more cross-tumor; they were tumor agnostic but were thematic focused. As I mentioned, those themes were really based on feedback that we had from prior attendees, as well as from the program committee's feeling on what are really the questions that we are dealing with and that are burning in the clinic today and that includes the emerging role of artificial intelligence and machine learning and how we integrate that into our clinical care, approaches to oligometastatic disease, and it's not really just something that we think of in colorectal cancer but haven't fully used that paradigm to really apply it to other GI malignancies. And then the art and science of clinical trial design where, again, traditional randomized phase 3 trials might not be the best and most innovative and most expedient way of bringing novel therapeutics to our patients. And so, I thought that all of those sessions were really highlighting different important topics that we deal with day to day. Additionally, we had a really fantastic keynote lecture from Dr. Kimmie Ng of the Dana-Farber Cancer Institute. She is a world-renowned expert in the early-onset colorectal cancer space, and the timing of her keynote was perfect with the new cancer statistics that came out literally days before GI ASCO that demonstrated this just dramatic rise in early onset GI malignancies as a whole, not just colorectal. And she spoke really in a comprehensive manner not just on clinical approaches, screening approaches, and how to find these patients at an earlier stage, but also kind of gave us a call to action, if you will, in terms of public health initiatives, as well as like I said, clinical care and really thinking outside of the box for how to reach these patients.  And then, of course, we always have what I think is one of my favorite aspects of the meeting, which are the networking opportunities that include the Trainee and Early Career Networking Luncheon, the Women's Networking Reception, and the Meet the Experts Luncheon where, especially as junior career investigators, you have an opportunity to meet what we think of as the “big names” in GI cancer. Dr. Shaalan Beg: Absolutely, I remember my first couple of GI ASCO meetings and those were probably the most memorable sessions that I attended as junior faculty as well.   So let's take a deeper dive into some key abstracts from the meeting. I'd like to begin with Abstract 245. This is the SKYSCRAPER-08 study. It's first-line tiragolumab and atezolizumab with chemotherapy in an Asian patient population with esophageal squamous cell carcinoma. What are your key takeaways from this study?  Dr. Rachna Shroff: Yeah. This was an exciting study in my opinion in the sense that thinking through how we can build on immunotherapy backbones is obviously a pressing question across the GI cancer space. So this was a phase 3 randomized, double-blinded, placebo-controlled trial that looked specifically at patients with esophageal squamous cell carcinomas. And the study was enrolled fully with an Asian population. It looked at taking the traditional chemotherapy backbone and adding to it an anti-PD-L1 with atezolizumab and an anti-TIGIT with tiragolumab. Again, that proof of principle of using anti-TIGIT and PD-L1 has been looked at across a lot of different GI cancer spaces and we know that the esophageal squamous cell cancers tend to be very immunotherapy responsive. So this was a really important question.  This involved a number of patients, a little over 460 patients, who were randomized one-to-one to receive the tiragolumab with atezolizumab with the standard paclitaxel and cisplatin, that's used for esophageal squamous versus chemotherapy alone with placebo. And the primary endpoint was independent review of progression-free survival, and overall survival. And so, out of the 461 patients randomized, there was at the primary analysis, a median improvement in progression free survival, from 5.4 months in the control arm to 6.2 months with a tira-paclitaxel plus chemo arm with a hazard ratio of 0.56, highly statistically significant. Similarly the median overall survival was also improved from 11.1 months to 15.7 months again with a hazard ratio of 0.7 and some of the other key efficacy endpoints were also improved with the addition of the anti-TIGIT PD-L1 approach. And importantly, there was not really safety signals that jumped out at us.  And so, to me, what this means is that, in our patients with esophageal squamous cell carcinoma, we really should be thinking about chemotherapy with immunotherapy as a backbone and how we can build on it. And, you know, I would imagine that it's hard to argue with both the PFS and OS endpoint that adding anti-TIGIT won't necessarily be kind of the new approach to these patients. And importantly, I'll point out that it seems to be a benefit across the subgroups, including PD-1 status, which is always our big question here. I think the only thing to keep in mind is this was an all-Asian population and whether or not that kind of immune profile of the immune responsiveness is different in those patients, but regardless, a positive phase 3 trial. Dr. Shaalan Beg: It's really exciting to see immune checkpoint inhibitors or immunotherapy beyond PD-1 targeted, CTLA-4 targeted treatments making their way into GI Cancers.  Dr. Rachna Shroff: Absolutely. Dr. Shaalan Beg: Sticking with the immunotherapy theme, let's focus on hepatocellular carcinoma. So LBA432, the EMERALD-1 study of transarterial chemoembolization combined with durva with or without bevacizumab looked at people with unresectable hepatocellular carcinoma eligible for embolization. So really a highly anticipated study, I'm wondering what your thoughts are and whether it'll be practice-changing for this field.  Dr. Rachna Shroff: I was excited to see the press release when it showed that the study was positive, and I think it's because now that we're using immunotherapy in the advanced HCC space, our obvious question is, can we integrate it into multimodality approaches? There are a lot of smaller studies looking at neoadjuvant IO approaches, and in this intermediate stage, unresectable hepatocellular carcinoma patients. We wanted to know if there was a utility to liver directed therapy with immunotherapy.  So, this was a large study. It was a global study looking at unresectable HCC with preserved Child-Pugh function. But it was Child-Pugh A and up to B7, importantly. And there were 616 patients randomized in a 1:1:1 fashion, with the control arm being just TACE alone. But then, there was also an opportunity for durvalumab with TACE, as well as durvalumab plus bevacizumab with TACE. The patients would receive durvalumab during their TACE treatments and could receive up to four TACE treatments and then subsequently were either continued on durvalumab alone, durvalumab plus bevacizumab, or the placebo. The primary endpoint was progression-free survival, powered specifically to look at TACE versus durvalumab plus TACE. In this study, the primary endpoint was met with a significant improvement in PFS. Median PFS was 15 months versus 8.2 months, with a hazard ratio of 0.77. Most prespecified subgroups demonstrated this benefit.  Importantly, there was a secondary endpoint looking at durvalumab plus TACE versus TACE alone, and that actually did not show a statistically significant improvement in median PFS from 8.2 months in the control arm to 10.0 months. The overall response rates were slightly higher with the durvalumab plus bevacizumab approach at 43.6%. And importantly in these patients, who oftentimes have a higher burden of disease in the liver, median time to progression is a really important and clinically meaningful endpoint. That was 22 months with the durvalumab plus bevacizumab and TACE versus 10 months for TACE alone. I would just point out that the overall concern we always have with bevacizumab is the increased risk of bleeding and the treatment-related adverse event profile. Overall, there were no safety signals that emerged from this, with nothing that really, especially in that bleeding risk category, jumped out at us. Of course, we haven't seen the overall survival data yet because we have not seen enough follow-up to really see that number.  I do think that this is potentially practice-changing, and I think it just demonstrates that there's probably some synergy between anti-VEGF with anti-PD-1, and then the liver-directed treatments. The obvious question for us in the United States is that the vast majority of people are moving away from TACE and towards more radioembolization and what can we extrapolate from this? Does this really tell us much if people are using more of a Y90-based approach? I think those are a lot of the burning questions that most of us have.  Dr. Shaalan Beg: Yeah, and it's a very interesting direction that the HCC space is taking because we heard in previous meetings, the role of PD-1 inhibition as adjuvant therapy after resection. Now, we have data for local-regionally advanced disease over local-regional treatments. And of course, you already mentioned the data for more advanced disease. So it sounds like immunotherapy may be impacting the management of anyone diagnosed with hepatocellular carcinoma.  Let's talk about the MONET trial, Abstract 249, which compared thoracoscopic esophagectomy and open esophagectomy for thoracic esophageal cancer. Do you think this is a study which may influence the treatment of patients with thoracic esophageal cancer? Dr. Rachna Shroff: So, this was, again, I think, a really important question. It was a randomized, controlled phase 3 trial comparing a more minimally invasive approach with TE — thoracoscopic esophagectomy — versus an open approach. This had patients with clinical stage 1-3, excluding T4 thoracic esophageal squamous cell carcinomas. They were randomized 1:1 to the open versus the TE approach, with a primary endpoint of overall survival and an important secondary endpoint of relapse-free survival. 300 patients were randomized, and at the second planned interim analysis, the median follow-up was a little over two and a half years. The 3-year overall survival was 82% in the TE group versus 70.9% in the open group. The DSMC of this trial actually recommended early termination based on the non-inferiority, which is what they were specifically looking at. There was a very statistically significant one-sided p-value for non-inferiority.  Importantly, the 3-year recurrence-free survival was also markedly better in the TE group versus the open group, with no real notable differences in R0 resection, or a large percentage of patients who needed to be converted from a TE to an open approach, and really not any significant difference in overall postoperative morbidity. I think this just supports the concept that minimally invasive approaches for our patients with GI malignancies can and should be considered. Again, esophageal squamous because they tend to be seen a lot more in Asia, this study was conducted in Japan, but I think that being said, a lot of our surgeons in Europe and in the U.S. are also very amenable to minimally invasive approaches. And I think this just supports the fact that an open approach is not necessary. So, I would think again, that this is something that is implementable and I think will affect the field.  Dr. Shaalan Beg: Moving on to metastatic cholangiocarcinoma, there have been many FGFR inhibitors that have shown activity and promise and are approved for the management of cholangiocarcinoma with FGFR alteration. But at this ASCO GI, we heard the results of the safety and efficacy of an FGFR1, 2, and 3 inhibitor, tinengotinib, as monotherapy for advanced metastatic cholangiocarcinoma (Abstract 434). How do you see this fitting into the broad picture? Dr. Rachna Shroff: Yeah, so this was highly anticipated data, primarily because at this point, the FGFR space in cholangiocarcinoma is quite crowded. And so a lot of us were getting sick of the "me-too" drugs. What is really unique about tinengotinib is that, not only is it a selective multikinase inhibitor, but it also, in preclinical models as well as in early phase one trials, demonstrated potent inhibition of patients with FGFR2 fusions and rearrangements who had acquired resistance mutations. So, as we better understand the first generation of FGFR inhibitors and note the resistance mechanisms, these drugs are now being developed to try to circumvent or overcome those.  This study looked at 4 different cohorts: 1 cohort with FGFR2 fusion patients who had primary progression who never responded to FGFR inhibitors, a second cohort with FGFR2 fusion patients who had progression after primary response, so those with acquired resistance, and then there was non-fusion FGFR alterations because we do know that a number of cholangiocarcinoma patients have other FGFR alterations that are not fusions, and then those with FGFR wild-type. The primary endpoint was objective response rate, with a total of 48 patients enrolled across the four cohorts. And so the 40 patients who were evaluable in the group that had primary resistance, which was the first cohort, there was a response rate was 9.1% and that was partial response, and 31% had tumor reduction with tinengotinib. And similarly in those with acquired resistance, 37.5%, 3 out of 8 patients had a partial response and tumor reductions were noted with an overall disease control rate between those patients with FGFR2 fusions of 94.7%, between those with primary and secondary resistance.  In the patients who had FGFR alterations, there was 3 out of 9 patients with a partial response and again, tumor reductions were notable across the board and the disease control rate was 88.9%. The FGFR wild-type group, not surprisingly, did not see any partial responses, but interestingly, 75% of these patients had at least disease control, and the median progression-free survival was 5.26 months, again, kind of most notably impressive in the 2 cohorts that included FGFR2 fusions. The toxicity profiles are what we come to expect for FGFR inhibitors and we've gotten better at managing those and mitigating some of those so there was really nothing to jump out there. So there is now an ongoing randomized phase III trial specifically looking at tinengotinib versus physician's choice in patients with FGFR2-altered cholangiocarcinoma after having received prior FGFR inhibitors. So that's where I think it's in is for those of us who know that there are multiple drugs in the space, our big question is can we sequence through that? Can we offer multiple FGFR inhibitors in these patients? And I think we are all eagerly anticipating this data as well as the subsequent data to really justify the use of these novel second generation FGFR inhibitors.  Dr. Shaalan Beg: It's been fantastic to see the evolution of these compounds in precision medicine, or precision oncology at its finest, in terms of understanding mechanisms of resistance and treating refractory disease.   Let's focus on colorectal cancer. I'll tell you, there has been a lot of discussion, Dr. Shroff, on social media, on insurance companies sometimes rejecting one biologic or the other based on tumor sidedness. We have talked about tumor sidedness predicting response on this podcast based on data from previous studies. But this year in GI ASCO, Abstract 207 explored the role of tumor genomics and tumor sidedness and they said that it's tumor genomics, that tumor genomics better explains the differences on outcomes, and it explains it better than sidedness. What does this mean to the field? Because a lot of professional organizations have guidelines that are asking people to now incorporate sidedness. So how does that change based on these results? Dr. Rachna Shroff: I really commend these authors on leveraging real-world data, and I think we're getting better and better at recognizing that real world data actually informs our clinical decision making, possibly better than sometimes some of these studies that lead to the guidelines and algorithms that we develop. So this is a perfect example of a little bit cart before horse in trying to understand the way that sidedness and genomics may interplay.   So this was a study that basically leveraged both the Foundation Medicine and Flatiron Health clinical genomic database and looked at patients with microsatellite stable metastatic colorectal cancer. There were a total of 3,845 patients included in a kind of two-thirds one-third split between left sided and right-sided colorectal cancer. And they found the typical genomic alterations that historically have been thought of more with left-sided colorectal cancer like APC and then more of the RAS BRAF alterations in the right-sided patients. But I think what they really thought and what I think was remarkable is they really looked at the patients and how they received chemotherapy with anti-EGFR or bevacizumab therapies, and they did a multivariate analysis to really see what is driving outcomes. And like you mentioned, what they found was patients in the RAS pathway, those classified as having alterations in the RAS pathway, had less favorable outcomes, while those with APC altered group had more favorable outcomes. And that was regardless of treatment received and sidedness.  And so when they did an analysis of what was called a “likelihood ratio test,” they found that when genomics was added to the sidedness evaluation, there was an improvement in outcome prediction, but not when sidedness was added to genomics. Like you said, it kind of demonstrates, at least in this mining of real-world data from Flatiron that tumor genomics is probably a better driver and a more important driver in determining outcomes than sidedness.  I totally agree with you. I would push for us to really kind of bring a little bit of noise to this and to make insurance companies and other companies that are looking at this to think through this a little bit more and make sure that we're putting all of the data together in a comprehensive passion before making the treatment plans and determinations. Dr. Shaalan Beg: The last abstract I'd like to ask you about is Abstract 117, the NEST-1 trial. This study looked at neoadjuvant botensilimab and balstilimab for resectable mismatch repair proficient and deficient colorectal cancer, both MSS and MSI. What are your key takeaways from this study?  Dr. Rachna Shroff: This is another study that is demonstrating that there may potentially be a role for immunotherapy in microsatellite stable patients. I will make the caveat that this was a single-arm study that really was looking at feasibility safety, with efficacy as a secondary endpoint. The combination of bot-bal in the neoadjuvant space for colorectal cancer patients, they received one dose of boten and two fixed doses of bal two weeks apart and then were taken to surgery. They limited the number of patients and out of the 12 patients that were enrolled, they limited the number of mismatch repair deficient patients. So to your point, they allowed both, but they wanted to make sure it was not just MSI-high patients. What they basically found is that it was safe and did not delay surgery or increase risks of adverse events. But importantly, there was significant regression of tumor noted. And some interesting spatial biology analyses demonstrated potentially novel mechanisms of action, especially in the MSS population, and that ctDNA reductions correlated with pathologic response. There were a lot of different things that they were looking at, basically suggesting that bot-bal is safe and can be used in both mismatch repair–deficient and proficient patients with colorectal cancer. And now importantly, they've added some additional cohorts and expanding the study. As I mentioned, this is right now just 12 patients, but does definitely have a provocative result.  Dr. Shaalan Beg: Thanks so much, Dr. Shroff.  Finally, the role of cell-free DNA (cfDNA) in GI cancers has been an exciting and important development in our field. There's tremendous data that emerged at the GI meeting, and we have decided to do a separate ASCO Daily News Podcast dedicated to ctDNA. So listeners, please look out for our coverage of key studies on ctDNA in GI cancers very soon here on the ASCO Daily News Podcast.  Many thanks, Dr. Shroff, for sharing your insights with us today and for your great work in building a robust GI meeting this year. Thank you very much. Dr. Rachna Shroff: Thank you so much. Dr. Shaalan Beg: And thank you to all our listeners for your time today. You'll find links to the abstracts discussed on the transcript of this episode. 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 inform. It is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Our guests on this podcast express their own opinions, experiences, and conclusions. These statements do not necessarily reflect the views of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an endorsement by ASCO.   Find out more about today's speakers: Dr. Shaalan Beg @ShaalanBeg Dr. Rachna Shroff @rachnatshroff   Follow ASCO on social media:  @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures: Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals   Dr. Rachna Shroff: Consulting or Advisory Role: Exelixis, Merck, QED Therapeutics, Incyte, Astra Zeneca, Taiho Pharmaceutical, Boehringer Ingelheim, SERVIER, Genentech, Basilea Research Funding: Pieris Pharmaceuticals, Taiho Pharmaceutical, Merck, Exelixis, QED Therapeutics, Rafael Pharmaceuticals, Bristol-Myers Squibb, Bayer, Immunovaccine, Seagen, Novocure, Nucana, Loxo/Lilly, Faeth Therapeutics

Success at multimodal, multi-indication, deep-pipelined Incyte—where commercial operations are as familiar as pre-discovery activity is—begins at the earliest opportunity to achieve research and discovery efficiencies. The company's a bit larger than those we typically cover on the Business of Biotech, and that's okay! Sometimes, the smartest approach to creating your own masterpiece is to study the masters On this episode of the podcast, we sit down with Incyte's Group Vice President and head of its Inflammation and AutoImmunity Group, Jim Lee, M.D., Ph.D. for a dissection of the company's approach to the comprehensive and efficient R&D that leads to repeated clinical and commercial success. Subscribe to the #BusinessofBiotech newsletter at bioprocessonline.com/bob for more real, honest, transparent interactions with the leaders of emerging biotech. It's a once-per-month dose of insight and intel that you'll actually look forward to receiving! Check it out at bioprocessonline.com/bob!

En este episodio de "De Piel a Cabeza", nos sumergimos a fondo en el VITÍLIGO, una enfermedad que "dibuja" nuestra piel con pinceladas únicas. Exploramos el vitiligo desde todos los ángulos, abordando tanto su impacto mental como sus diversas manifestaciones en la piel. Desde las causas y tratamientos hasta las experiencias personales en consulta, nuestro objetivo es generar conciencia sobre esta condición que lleva consigo un mensaje de aceptación y desestigmatización.Porque el vitiligo es más que simplemente "manchas blancas en la piel". Es una condición cutánea crónica y no contagiosa que a menudo lleva consigo una carga emocional significativa. Por eso también profundizamos en el impacto en la autoestima, explorando cómo esta enfermedad condiciona la percepción individual de la belleza y la confianza en uno mismo. Acompáñanos en este viaje de conocimiento, donde el vitiligo se convierte en un lienzo para celebrar la diversidad y la belleza única de cada individuo. Este episodio de "De Piel a Cabeza" es posible gracias al generoso apoyo de Incyte, una empresa comprometida con la investigación y el desarrollo de tratamientos innovadores para condiciones dermatológicas como el vitiligo. Gracias a su apoyo, podemos seguir brindando información valiosa y perspectivas inspiradoras sobre el vitiligo, ofreciendo un espacio de aprendizaje y crecimiento para nuestra comunidad. Hosted on Acast. See acast.com/privacy for more information.

A great week on The Nikki & Brie Show continues as USWNT soccer legend Mia Hamm joins them for an exceptional conversation that covers her career on the field, her perspective on being a mother, her work to raise awareness for bone marrow transplants and the special connection she has to the bone marrow transplant community. For years Nikki & Brie have been putting it out in the universe that they wanted to get Mia Hamm on the podcast. Growing up in Arizona and playing soccer, they both looked up to the USWNT that won multiple World Cups and Olympic Gold medals, and created a path of empowerment and achievement in life. Mia talks about the responsibility and opportunity that the team embraced, knowing that young eyes across the country were watching their every move, raising twin girls, filming a legendary Gatorade commercial with Michael Jordan and what his support meant, exhausting practices that tested her mental fortitude, and how she was introduced to the game of soccer, and the WWE superstar that used to throw her into a pool as a kid that went on to also have a Hall of Fame career. Mia also highlights the importance of her big brother Garrett, whom she admired greatly, who passed away in 1997 from complications following a bone marrow transplant (BMT) his family hoped could help cure aplastic anemia, a rare bone marrow disease he was battling at the time, which is why bone marrow transplant support and gave her a new mission in life to help other families, teaming up with Incyte to make sure they get the tools and information they need with a procedure that can have serious complications like Graft Versus Host Disease (GVHD). Mia closes out the episode with a special Inspiration & Affirmation that focuses on being present in a world that's full of distractions. For more on Mia's work with BMT and GVHD check out this link Find out more about bone marrow transplants at The Mia Hamm Foundation Follow Mia on Instagram Call Nikki & Brie at 833-GARCIA2 and leave a voicemail!Follow Nikki & Brie on Instagram and send Nikki & Brie a message on Threads!To watch exclusive videos of this week's episode, follow The Nikki & Brie Show on YouTube, Facebook, and TikTok!