Podcasts about elevation oncology

In the previous episode we heard how some rationally-designed therapies work on almost any cancer with the right molecular signature. Tumour-agnostic medications could be godsend for patients with rare cancers which have classically been overlooked by drug developers, and those with advanced cancers of unknown origin. 15,000 such patients have undergone comprehensive genome profiling of their tumours through the organisation, Omico. In this podcast, Omico's founder explains that while the majority have received recommendations about matched therapies, clinical trials are typically the only way to enable access. Professor David Thomas discusses why Australia's Health Technology Assessment process appears to be so conservative and how the market price of next-generation oncotherapies might be brought down by changes across the local ecosystem. Guest Prof David Thomas FRACP PhD (Director, Centre for Molecular Oncology UNSW; Founder and Chief of Science, Omico)  Professor Thomas or Omico have received grants, consultancies or research support from Roche, Astra Zeneca, Pfizer, Eisai, Illumina, Beigene , Elevation Oncology, RedX Pharmaceuticals, SunPharma , Bayer, George Clinical, Novotech , Merck Sharpe and Dohme, Boehringer Ingelheim, Hummingbird, Microba , BioTessellate , PMV Pharma, Australian Unity and Foundation Medicine. ProductionProduced by Mic Cavazzini DPhil. Music licenced from Epidemic Sound includes  ‘Multicolor' and ‘Pulse Voyage' by Chill Cole. ‘Impulsing', ‘the City of Hope' ‘Over Again', and ‘Going Undercover' by Borrtex provided courtesy of FreeMusicArchive. Image by Guido Mieth licenced through Getty Images.  Editorial feedback kindly provided by RACP physicians Simeon Wong, Stephen Bacchi. Thanks also to Kym Bramich and Arnika Martus on staff with Omico and RACP respectively.  Please visit the Pomegranate Health web page for a transcript and supporting references.Login to MyCPD to record listening and reading as a prefilled learning activity. Subscribe to new episode email alerts or search for ‘Pomegranate Health' in Apple Podcasts, Spotify,Castbox or any podcasting app.

The genomic understanding of cancer has transformed a tissue-based classification model that had been dominant for 150 years or more. The last three decades have seen highly targeted therapies developed at blistering pace, and unprecedented improvements in patient outcomes. To date, these advances have been focused on more common cancers. The financing model for drug development means that rare cancers get overlooked, given the small pool of potential buyers relative to the costs and risks of investment. However, the molecular targets characterised in more common cancers are often found in cancers of a different histotype. As such, precision therapies will sometimes have tissue-agnostic efficacy and offer a lifeline for patients with neglected diseases or cancers of unknown origin. Professor David Thomas has founded an NGO called Omico to enable such patients to undergo profiling for hundreds of potential molecular targets. In this interview he explains the rationale for the most promising pan cancer therapies, and in the next episode we discuss changes to the regulatory and funding model required to sustain this screening program. Guest Prof David Thomas FRACP PhD (Director, Centre for Molecular Oncology UNSW; Founder and Chief of Science, Omico) Professor Thomas or Omico have received grants, consultancies or research support from Roche, Astra Zeneca, Pfizer, Eisai, Illumina, Beigene , Elevation Oncology, RedX Pharmaceuticals, SunPharma , Bayer, George Clinical, Novotech , Merck Sharpe and Dohme, Boehringer Ingelheim, Hummingbird, Microba , BioTessellate , PMV Pharma, Australian Unity and Foundation Medicine. ProductionProduced by Mic Cavazzini DPhil. Music licenced from Epidemic Sound includes ‘the Orchard' by Jakob Ahlbom, ‘Dusty Electronics' and ‘Pulse Voyage' by Chill Cole, ‘Tam' by LJ Kruzer, ‘See you soon' and ‘Going Undercover' by Borrtex. Image by filo licenced through Getty Images. Editorial feedback was kindly provided by RACP physicians Nichola Ball, Stephen Bacchi, Aafreen Khalid, Simeon Wong, Maansi Arora and Aidan Tan.Please visit the Pomegranate Health web page for a transcript and supporting references.Login to MyCPD to record listening and reading as a prefilled learning activity. Subscribe to new episode email alerts or search for ‘Pomegranate Health' in Apple Podcasts, Spotify,Castbox or any podcasting app.

Joe Ferra, CEO of Elevation Oncology, highlights the unmet needs in gastric cancer and the potential of targeting Claudins, proteins involved in cell adhesion. The current competitive landscape of antibody drug conjugates (ADCs) confirms the promise of a targeted therapy that delivers a cytotoxic drug directly to cancer cells. Targeting Claudin 18.2 with an ADC approach offers an opportunity to treat a broader range of tumors expressing a lower level of Claudin 18.2 than those currently treated by CAR-T therapy. This approach is being investigated as a single-agent drug with promise for use in combination for gastric cancer, pancreatic cancer and esophageal cancer. Joe explains, "As you likely know, in the continuum of cancer drugs, you have chemotherapy on one end that indiscriminately kills everything it touches. On the other end, you have uber-targeted therapies looking at specific drivers of what's driving that specific tumor. In our case at Elevation Oncology, we're focused on what we like to call selected targeted oncology drugs so that we are using the unique characteristics of the tumor to target and meet in a targeted way attempt to kill the tumor for a better outcome for the patient." "Gastric cancer in and of itself was an area where Claudin 18.2 is known to be highly expressed, but for gastric cancer, to your point, there's a huge unmet need. For most patients, once they're in second line or third line, the opportunity for drugs that are available to them today is, unfortunately for all of us, very dismal. We think there's a significant opportunity to utilize a Claudin 18.2 antibiotic drug conjugate for overall better outcomes for patients living with gastric cancer." "We quickly saw an ADC approach as an opportunity to treat a broader range of Claudin 18.2 expression. Now, as I'm sure you're aware, in any target in any tumor, there's always a range of expression for Claudin 18.2. In gastric cancer, it's known that as much as 80% of gastric cancer expressed Claudin 18.2 at some level. With that expression, we think an ADC approach will be able to treat a broader range of expression." #ElevationOncology #ADC #AntibodyDrugConjugate #SolidTumors #Claudin182 #Claudins #Cancer ElevationOncology.com Download the transcript here 

Joe Ferra, CEO of Elevation Oncology, highlights the unmet needs in gastric cancer and the potential of targeting Claudins, proteins involved in cell adhesion. The current competitive landscape of antibody drug conjugates (ADCs) confirms the promise of a targeted therapy that delivers a cytotoxic drug directly to cancer cells. Targeting Claudin 18.2 with an ADC approach offers an opportunity to treat a broader range of tumors expressing a lower level of Claudin 18.2 than those currently treated by CAR-T therapy. This approach is being investigated as a single-agent drug with promise for use in combination for gastric cancer, pancreatic cancer and esophageal cancer. Joe explains, "As you likely know, in the continuum of cancer drugs, you have chemotherapy on one end that indiscriminately kills everything it touches. On the other end, you have uber-targeted therapies looking at specific drivers of what's driving that specific tumor. In our case at Elevation Oncology, we're focused on what we like to call selected targeted oncology drugs so that we are using the unique characteristics of the tumor to target and meet in a targeted way attempt to kill the tumor for a better outcome for the patient." "Gastric cancer in and of itself was an area where Claudin 18.2 is known to be highly expressed, but for gastric cancer, to your point, there's a huge unmet need. For most patients, once they're in second line or third line, the opportunity for drugs that are available to them today is, unfortunately for all of us, very dismal. We think there's a significant opportunity to utilize a Claudin 18.2 antibiotic drug conjugate for overall better outcomes for patients living with gastric cancer." "We quickly saw an ADC approach as an opportunity to treat a broader range of Claudin 18.2 expression. Now, as I'm sure you're aware, in any target in any tumor, there's always a range of expression for Claudin 18.2. In gastric cancer, it's known that as much as 80% of gastric cancer expressed Claudin 18.2 at some level. With that expression, we think an ADC approach will be able to treat a broader range of expression." #ElevationOncology #ADC #AntibodyDrugConjugate #SolidTumors #Claudin182 #Claudins #Cancer ElevationOncology.com Listen to the podcast here 

Drs. Vamsi Velcheti and Nathan Pennell discuss novel approaches and key studies in lung cancer that were showcased at the 2024 ASCO Annual Meeting, including the Plenary abstracts LAURA and ADRIATIC.   TRANSCRIPT Dr. Vamsi Velcheti: Hello, I am Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I'm a professor of medicine and director of thoracic medical oncology at the Perlmutter Cancer Center at NYU Langone Health. Today, I'm joined by Dr. Nate Pennell, the co-director of the Cleveland Clinic Lung Cancer Program and the vice chair of clinical research at the Taussig Cancer Center in Cleveland Clinic. Dr. Pennell is also the editor-in-chief of the ASCO Educational Book. Today, we will be discussing practice-changing abstracts and the exciting advances in lung cancer that were featured at the ASCO 2024 Annual Meeting. You'll find our full disclosures in the transcript of the episode. Nate, we're delighted to have you back on the podcast today. Thanks for being here. It was an exciting Annual Meeting with a lot of important updates in lung cancer. Dr. Nate Pennell: Thanks, Vamsi. I'm glad to be back. And yes, it was a huge year for lung. So I'm glad that we got a chance to discuss all of these late-breaking abstracts that we didn't get to talk about during the prelim podcast. Dr. Vamsi Velcheti: Let's dive in. Nate, it was wonderful to see all the exciting data, and one of the abstracts in the Plenary Session caught my attention, LBA3. In this study, the investigators did a comparative large-scale effectiveness trial of early palliative care delivered via telehealth versus in-person among patients with advanced non-small cell lung cancer. And the study is very promising. Could you tell us a little bit more about the study and your take-home messages? Dr. Nate Pennell: Yes, I think this was a very important study. So just to put things in perspective, it's now been more than a decade since Dr. Jennifer Temel and her group at Massachusetts General Hospital did a randomized study that showed that early interventions with palliative medicine consultation in patients with advanced non-small cell lung cancer significantly improves quality of life and in her initial study, perhaps even overall survival. And since then, there have been numerous studies that have basically reproduced this effect, showing that getting palliative medicine involved in people with advanced cancer, multiple different cancer types, really, has benefits.  The difficulty in applying this has been that palliative care-trained specialists are few and far between, and many people simply don't have easy access to palliative medicine-trained physicians and providers. So with that in mind, Dr. Temel and her group designed a randomized study called the REACH PC trial, where 1,250 patients were randomized with advanced non-small cell lung cancer to either in-person palliative medicine visits which is sort of the standard, or one in-person assessment followed by monthly telemedicine video visits with palliative medicine. Primary endpoint was essentially to show that it was equivalent in terms of quality of life and patient satisfaction. And what was exciting about this was that it absolutely was. I mean, pretty much across the board in all the metrics that were measured, the quality-of-life, the patient satisfaction, the anxiety and depression scores, all were equivalent between doing telemedicine visits and in-person visits. And this hopefully will now extend the ability to get this kind of benefit to a much larger group of people who don't have to geographically be located near a palliative medicine program. Dr. Vamsi Velcheti: Yeah, I think it's a great abstract, Nate and I actually was very impressed by the ASCO committee for selecting this for the Plenary. We typically don't see supportive care studies highlighted in such a way at ASCO. This really highlights the need for true interdisciplinary care for our patients. And as you said, this study will clearly address that unmet need in terms of providing access to palliative care for a lot of patients who otherwise wouldn't have access. I'm really glad to see those results. Dr. Nate Pennell: It was. And that really went along with Dr. Schuchter's theme this year of bringing care to patients incorporating supportive care. So I agree with you.  Now, moving to some of the other exciting abstracts in the Plenary Session. So we were talking about how this was a big year for lung cancer. There were actually 3 lung cancer studies in the Plenary Session at the Annual Meeting. And let's move on to the second one, LBA4, the LAURA study. This was the first phase 3 study to assess osimertinib, an EGFR tyrosine kinase inhibitor, in patients with EGFR mutant, unresectable stage III non-small cell lung cancer. What are your takeaways from this study?  Dr. Vamsi Velcheti: This is certainly an exciting study, and all of us in the lung community have been kind of eagerly awaiting the results of the study. As you know, for stage III non-small cell lung cancer patients who are unresectable, the standard of care has been really established by the PACIFIC study with the consolidation durvalumab after definitive concurrent chemoradiation. The problem with that study is it doesn't really answer the question of the role of immunotherapy in patients who are never-smokers, and especially in patients who are EGFR positive tumors, where the role of immunotherapy in a metastatic setting has always been questioned. And in fact, there have been several studies as you know, in patients with EGFR mutation positive metastatic lung cancer where immunotherapy has not been that effective. In fact, in the subgroup analysis in the PACIFIC study, patients with EGFR mutation did not really benefit from adding immunotherapy.  So this is an interesting study where they looked at patients with locally advanced, unresectable stage III patients and they randomized the patients 2:1 to osimertinib versus placebo following concurrent or sequential tumor radiation. The primary endpoint for the study was progression free survival, and a total of 216 patients were enrolled and 143 patients received a study treatment, which is osimertinib, and 73 received placebo. And 80% of the patients on the placebo arm crossed over to getting treatment at the time of progression.  So most of us in the lung cancer community were kind of suspecting this would be a positive trial for PFS. But however, I think the magnitude of the difference was truly remarkable. The median PFS in the osimertinib arm was 39.1 months and placebo was 5.6 months and the hazard ratio of 0.16. So it was a pretty striking difference in terms of DFS benefit with the osimertinib consolidation following chemoradiation. So it was truly a positive study for the primary endpoint and the benefit was seen across all the subgroups and the safety was no unexpected safety signals other than a slight increase in the radiation pneumonitis rates in patients receiving osimertinib and other GI and skin tox were kind of as expected. In my opinion, it's truly practice changing and I think patients with EGFR mutation should not be getting immunotherapy consolidation post chemoradiation. Dr. Nate Pennell: I completely agree with you. I think that this really just continues the understanding of the use of osimertinib in EGFR-mutant lung cancer in earlier stages of disease. We know from the ADAURA trial, presented twice in the Plenary at the ASCO Annual Meeting, that for IB, stage II and resectable IIIA, that you prolong progression free or disease free survival. So this is a very similar, comparable situation, but at an even higher risk population or the unresectable stage III patients. I think that the most discussion about this was the fact that the osimertinib is indefinite and that it is distinct from the adjuvant setting where it's being given for three years and then stopped. But I think all of us had some pause when we saw that after three years, especially in the stage III patients from ADAURA, that there were clearly an increase in recurrences after stopping the drug, suggesting that there are patients who are not cured with a time limited treatment, or at least with 3 years of treatment.  The other thing that is sobering from the study, and was pointed out by the discussant, Dr. Lecia Sequist, is if you look at the two-year disease-free survival in the placebo arm, it was only 13%, meaning almost no one was really cured with chemo radiation alone. And that really suggests that this is not that different from a very early stage IV population where indefinite treatment really is the standard of care. I wonder whether you think that's a reasonable approach. Dr. Vamsi Velcheti: I completely agree with you, Nate, and I don't think we cure a majority of our patients with stage III, and less so in patients who have EGFR-mutant, stage III locally advanced. As you just pointed out, I think very few patients actually make it that far along. And I think there's a very high rate of CNS micrometastatic disease or just systemic micrometastatic disease in this population that an effective systemic therapy of osimertinib can potentially have long term outcomes. But again, we perhaps don't cure a vast majority of them. I think that the next wave of studies should incorporate ctDNA and MRD-based assays to potentially identify those patients who could potentially go off osimertinib at some point. But, again, outside of a trial, I would not be doing that. But I think it's definitely an important question to ask to identify de-escalation strategies with osimertinib. And even immunotherapy for that matter, I think we all know that not all patients really require years and years of immunotherapy. They're still trying to figure out how to use immunotherapy in these post-surgical settings, using the MRD to de-escalate adjuvant therapies. So I think we have to have some sort of strategy here. But outside of a clinical trial, I will not be using those assays here to cite treatments, but certainly an important question to ask.  Moving on to the other exciting late-breaking abstracts, LBA5, the ADRIATIC study. This is another study which was also in the plenary session. This study was designed to address this question of consolidation immunotherapy, post chemo radiation for limited-stage small cell cancer, the treatment arms being durvalumab tremelimumab, and durvalumab observation. So what do you think about the study? This study also received a lot of applause and a lot of attention at the ASCO meeting. Dr. Nate Pennell: It was. It was remarkable to be there and actually watch this study as well as the LAURA study live, because when the disease free survival curves and in the ADRIATIC study, the overall survival curves were shown, the speakers were both interrupted by standing ovation of applause just because there was a recognition that the treatment was changing kind of before our eyes. I thought that was really neat. So in this case, I think this is truly a historic study, not necessarily because it's going to necessarily be an earth shakingly positive study. I mean, it was clearly a positive study, but more simply because of the disease in which it was done, and that is limited-stage small cell lung cancer. We really have not had a change in the way we've treated limited-stage small cell lung cancer, probably 25 years. Maybe the last significant advances in that were the advent of concurrent chemotherapy and radiation and then the use of PCI with a very modest improvement in survival. Both of those, I would say, are still relatively modest advances.  In this case, the addition of immunotherapy, which we know helps patients with small cell lung cancer - it's of course the standard of care in combination chemotherapy for extensive stage small cell lung cancer - in this case, patients who completed concurrent chemo radiation were then randomized to either placebo or durvalumab, as well as the third arm of durvalumab tremelimumab, which is not yet been recorded, and co primary endpoints were overall survival and progression free survival. And extraordinarily, there was an improvement in overall survival seen at the first analysis, with a median overall survival of 55.9 months compared to 33.4 months, hazard ratio of 0.73. So highly clinically and statistically significant, that translates at three years to a difference in overall survival of 56.5%, compared to 47.6%, or almost 10% improvement in survival at three years.  There was also a nearly identical improvement in progression-free survival, also with a hazard ratio of 0.76, suggesting that there's a modest number of patients who benefit. But it seems to be a clear improvement with the curves plateauing out. In my opinion, this is very comparable to what we saw with the PACIFIC study in stage III, unresectable non-small cell lung cancer, which immediately changed practice back when that first was reported. And I expect that this will change practice pretty much immediately for small cell as well. Dr. Vamsi Velcheti: Yeah, I completely agree, Nate. I think it's an exciting advance in patients with limited-stage small cell lung cancer. For sure, it's practice-changing, and I think the results were exciting.  So one thing that really intrigued me was in the extensive-stage setting, the benefit was very mediocre with one-to-two month overall survival benefit in both the PACIFIC and in IMpower trial. Here we are seeing almost two-year of median OS benefit. I was kind of puzzled by that, and I thought it may have to do with patients receiving radiation. And we've seen that with the PACIFIC, and makes you wonder if both the CASPIAN and the IMpower studies actually did not allow consolidation thoracic radiation. Hypothetically, if they had allowed consolidation thoracic radiation, perhaps we would have seen better outcomes. Any thoughts on that? Dr. Nate Pennell: We've been trying to prove that radiation and immunotherapy somehow go together better for a long time. Going back to the first description of the abscopal effect, and I'm not sure if I necessarily believe that to be the case, but in this setting where we truly are trying to cure people rather than merely prolong their survival, maybe this is the situation where it truly is more beneficial. I think what we're seeing is something very similar to what we're seen in PACIFIC, where in the stage IV setting, some people have long term survival with immunotherapy, but it's relatively modest. But perhaps in the curative setting, you're seeing more of an impact. Certainly, looking at these curves, we'll have to see with another couple of years to follow up. But a three-year survival of 56% is pretty extraordinary, and I look forward to seeing if this really maintains over the next couple of years follow up.  Moving beyond the Plenary, there were actually lots of really exciting presentations, even outside the Plenary section. One that I think probably got at least as much attention as the ones that we've already discussed today was actually an update of an old trial that's been presented for several prior years. And I'm curious to get your take on why you thought this was such a remarkable study. And we're talking about the LBA8503, which was the 5-year update from the CROWN study, which looked at previously untreated ALK-positive advanced non-small cell in cancer patients randomly assigned to lorlatinib, the third generation ALK inhibitor, versus crizotinib, the first generation ALK inhibitor. What was so exciting about this study, and why were people talking about it?  Dr. Vamsi Velcheti: Yeah, I agree, Nate. We've seen the data in the past, right? Like on the CROWN data, just first like a quick recap. This is the CROWN study, like the phase 3 study of third generation ALK inhibitor lorlatinib. So global randomized phase 3 study in patients with metastatic disease randomized to lorlatinib versus crizotinib, which is a controller. So the primary endpoint was PFS, and we've seen the results in the past of the CROWN readout quoted, with a positive study and the lorlatinib received FDA approval in the frontline setting. But the current study that was presented at the ASCO annual meeting is a kind of a postdoc analysis of five years. The endpoint for the study with central review stopped at three years, and this is actually a follow up beyond that last readout. Interestingly, in this study, when they looked at the median PFS at five years, the lorlatinib arm did not reach a median PFS even at five years and the hazard ratio is 0.19, which is kind of phenomenal in some ways. At 5 years, the majority of the patients were still on the drug. So that's quite incredible. And the benefit was more profound in patients with brain mets with a hazard ratio of 0.08. And again, speaking to the importance of brain penetrant, small molecule inhibitors, and target therapy, the safety profile, there were no additional safety signals noted in the study. We kind of know about the side effects of lorlatinib already from previous studies readouts. No unusual long-term toxicities.  I should note though, about 40% of patients did have CNS, AEs grade 1, 2 CNS toxicities on the  lorlatinib arm. And the other interesting thing that was also reported in the trial was dose reduction of lorlatinib did not have an impact on the PFS, which is interesting in my opinion. They also did some subgroup analysis, biomarker testing, biomarker populations. Patients who had P53 cooperation did much better with lorlatinib versus crizotinib. So overall, the other thing that they also had shown on the trial was the resistance mechanisms that were seen with lorlatinib were very different than what we are used to seeing with the earlier generation ALK inhibitors. The majority of the patients who develop resistance have bypass mechanisms and alterations in MAP kinase pathway PI3K/MTOR/PTEN pathway, suggesting that lorlatinib is a very potent ALK inhibitor and on target ALK mutations don't happen as frequently as we see with the earlier generation ALK inhibitors.  So I think this really begs the question, should we offer lorlatinib to all our patients with metastatic ALK-positive tumors? I think looking at the long-term data, it's quite tempting to say ‘yes', but I think at the same time we have to take into consideration patient safety tolerability. And again, the competitor arm here is crizotinib. So lorlatinib suddenly seems to be, again, cross trial comparisons, but I think the long-term outcomes here are really phenomenal. But at the same time, I think we've got to kind of think about patient because these patients are on these drugs for years, they have to live with all the toxicities. And I think the patient preferences and safety profile matters in terms of what drug we recommend to patients. Dr. Nate Pennell: I completely agree with you. I think the right answer, is that this has to be an individual discussion with patients. The results are incredibly exciting. I mean, the two-year progression free survival was 70%, and the five-year, three years later is still 60%. Only 10% of people are failing over the subsequent three years. And the line is pretty flat. And as you said, even with brain metastases, the median survival is in reach. It's really extraordinary. Moreover, while we do talk about the significant toxicities of lorlatinib, I thought it was really interesting that only 5% of people were supposedly discontinued the drug because of treatment related AEs, which meant that with dose reduction and management, it seems as though most patients were able to continue on the drug, even though they, as you mentioned, were taking it for several years.  That being said, all of us who've had experience with the second-generation drugs like alectinib and brigatinib, compared to the third-generation drug lorlatinib, can speak to the challenges of some of the unique toxicities that go along with it. I don't think this is going to be a drug for everyone, but I do think it is now worth bringing it up and discussing it with the patients most of the time now. And I do think that there will be many people for whom this is going to be a good choice, which is exciting. Dr. Vamsi Velcheti: Absolutely, completely agree. And I think there are newer ALK inhibitors in clinical development which have cleaner and better safety profiles. So we'll have to kind of wait and see how those pan out.  Moving on to the other exciting abstract, LBA8509, the KRYSTAL-12 study. LBA8509 is a phase 3 study looking at adagrasib versus docetaxel in patients with previously treated advanced metastatic non-small cell cancer with KRASG12C mutation. Nate, there's been a lot of hype around this trial. You've seen the data. Do you think it's practice-changing? How does it differentiate with the other drug that's already FDA approved, sotorasib?  Dr. Nate Pennell: Yeah, this is an interesting one. I think we've all been very excited in recent years about the identification of KRASG12C mutations as targetable mutations. We know that this represents about half of KRAS mutations in patients with non-small cell lung cancer, adenocarcinoma, and there are two FDA-approved drugs. Sotorasib was the first and adagrasib shortly thereafter. We already had seen the CodeBreaK 200 study, which was a phase 3 study of sotorasib versus docetaxel that did modestly prolong progression free survival compared to docetaxel, although did not seem to necessarily translate to an improvement in overall survival. And so now, coming on the heels of that study, the KRYSTAL-12 study compared adagrasib, also the KRASG12C  inhibitor versus docetaxel and those with previously treated non-small cell with KRASG12C. And it did significantly improve progression free survival with a hazard ratio of 0.58. Although when you look at the median numbers, the median PFS was only 5.5 months with the adagrasib arm compared to 3.8 months with docetaxel. So while it is a significant and potentially clinically significant difference, it is still, I would say a modest improvement.   And there were some pretty broad improvements across all the different subgroups, including those with brain metastases. It did improve response rate significantly. So 32% response rate without adagrasib, compared to only 9% with docetaxel. It's about what you would expect with chemotherapy. And very importantly, in this patient population, there was activity in the brain with an intracranial overall response rate among those who had measurable brain metastases of 40%. So certainly important and probably that would distinguish it from drugs like docetaxel, which we don't expect to have a lot of intracranial toxicity. There is certainly a pattern of side effects that go along with that adagrasib, so it does cause especially GI toxicity, like diarrhea, nausea, vomiting, transaminitis. All of these were actually, at least numerically, somewhat higher in the adagrasib arm than in docetaxel, a lot more hematologic toxicity with the docetaxel. But overall, the number of serious adverse events were actually pretty well matched between the two groups. So it wasn't really a home run in terms of favorable toxicity with that adagrasib.  So the question is: “In the absence of any data yet on overall survival, should this change practice?” And I'm not sure it's going to change practice, because I do think that based on the accelerated approval, most physicians are already offering the G12C inhibitors like sotorasib and adagrasib, probably more often than chemotherapy, I think based on perceived improvement in side effects and higher response rates, modestly longer progression-free survival, so I think most people think that represents a modest improvement over chemotherapy. And so I think that will continue. It will be very interesting, however, when the overall survival report is out, if it is not significantly better, what the FDA is going to do when they look at these drugs.  Dr. Vamsi Velcheti: Thanks so much. Very well summarized. And I do agree they look more similar than dissimilar. I think CodeBreaK-200 and the KRYSTAL-12, they kind of are very identical. I should say, though I was a little surprised with the toxicity profile of adagrasib. It seemed, I mean, not significantly, but definitely seemed worse than the earlier readouts that we've seen. The GI tox especially seems much worse on this trial. I'm kind of curious why, but if I recall correctly, I think 5% of the patients had grade 3 diarrhea. A significant proportion of patients had grade 3 nausea and vomiting. And the other complicating thing here is you can't use a lot of the antiemetics because of the QT issues. So that's another problem. But I think it's more comparable to sotorasib, in my opinion.  Dr. Nate Pennell: While this is exciting, I like to think of this as the early days of EGFR, when we were using gefitinib and erlotinib. They were certainly advances, but we now have drugs that are much more effective and long lasting in these patients. And I think that the first-generation inhibitors like sotorasib and adagrasib, while they certainly benefit patients, now is just the beginning. There's a lot of research going on, and we're not going to talk about some of the other abstracts presented, but some of the next generation G12C inhibitors, for example, olomorasib, which did have also in the same session, a presentation in combination with pembrolizumab that had a very impressive response rate with potentially fewer side effects, may end up replacing the first generation drugs when they get a little bit farther along. And then moving on to another one, which I think potentially could change practice. I am curious to hear your take on it, was the LBA8505, which was the PALOMA-3 study. This was interesting in that it compared two different versions of the same drug. So amivantamab, the bispecific, EGFR and MET, which is already approved for EGFR exon 20 non-small cell lung cancer, in this case, in more typical EGFR-mutated non-small cell lung cancer in combination with osimertinib with the intravenous amivantamab, compared to the subcutaneous formulation of amivantamab. Why would this be an important study? Dr. Vamsi Velcheti: I found this study really interesting as well, Nate. And as you know, amivantamab has been FDA approved for patients with exon 20 mutation. And also, we've had, like two positive readouts in patients with classical EGFR mutations. One, the MARIPOSA study in the frontline setting and the MARIPOSA-2, in the second-line post osimertinib setting. For those studies, the intravenous amivantamab was used as a treatment arm, and the intravenous amivantamab had a lot of baggage to go along with it, like the infusion reactions and VTEs and other classic EGFR related toxicity, skin toxicities. So the idea behind developing the subcutaneous formulation of amivantamab was mainly to reduce the burden of infusion, infusion time and most importantly, the infusion related reactions associated with IV formulation.  In a smaller phase 2 study, the PALOMA study, they had looked at various dosing schemas like, subcutaneous formulation, and they found that the infusion related reactions were very, very low with the subcutaneous formulation. So that led to the design of this current study that was presented, the PALOMA-3 study. This was for patients who had classical EGFR mutations like exon 19, L858R. The patients were randomized 1:1 to subcutaneous amivantamab with lazertinib versus IV amivantamab plus lazertinib. The endpoints for the study, it's a non-inferiority study with co primary endpoints of C trough and C2 AUC, Cycle 2 AUC. They were looking at those pharmacological endpoints to kind of demonstrate comparability to the IV formulation. So in this study, they looked at these pharmacokinetic endpoints and they were essentially identical. Both subcutaneous and IV formulations were compatible. And in terms of clinical efficacy as well, the response rate was identical, no significant differences. Duration of response was also identical. The PFS also was comparable to the IV formulation. In fact, numerically, the subcutaneous arm was a little better, though not significant. But it appears like, you know, the overall clinical and pharmacological profile of the subcutaneous amivantamab was comparable. And most interestingly, the AE profile, the skin toxicity was not much different. However, the infusion reactions were substantially lower, 13% with the subcutaneous amivantamab and 66% with IV amivantamab. And also, interestingly, the VTE rates were lower with the subcutaneous version of amivantamab. There was still a substantial proportion of patients, especially those who didn't have prophylactic anticoagulation. 17% of the patients with the subcutaneous amivantamab had VTE versus 26% with IV amivantamab. With prophylaxis, which is lower in both IV and subcutaneous, but still subcutaneous formulation at a lower 7% versus 12% with the IV amivantamab.  So overall, I think this is an interesting study, and also the authors had actually presented some interesting data on administration time. I've never seen this before. Patients reported convenience using a modified score of patient convenience, essentially like patients having to spend a lot of time in the infusion site and convenience of the patient getting the treatment. And it turns out, and no surprise, that subcutaneous amivantamab was found to be more convenient for patients.  So, Nate, I want to ask you your take on this. In a lot of our busy infusion centers, the time it takes for those patients to get the infusion does matter, right? And I think in our clinic where we are kind of fully booked for the infusion, I think having the patients come in and leave in 15, 20 minutes, I think it adds a lot of value to the cancer center operation.  Dr. Nate Pennell: Oh, I completely agree. I think the efficacy results were reassuring. I think the infusion related reaction difference, I think is a huge difference. I mean, I have given a fair amount of amivantamab, and I would say the published IRR rate of 66%, 67% I would say, is maybe even underestimates how many patients get some kind of reaction from that, although it really is a first dose phenomenon. And I think that taking that down to 13% is a tremendous advance. I think fusion share time is not trivial as we get busier and busier. I know our cancer center is also very full and it becomes challenging to schedule people, and being able to do a five-minute treatment versus a five-hour treatment makes a big difference for patients.  It's interesting, there was one slide that was presented from an efficacy standpoint. I'm curious about your take on this. They showed that the overall survival was actually better in the subcu amivantamab arm, hazard ratio of 0.62. Now, this was only an exploratory endpoint. They sort of talk about perhaps some rationale for why this might be the case. But at the very least, I think we can be reassured that it's not less effective to give it and does seem to be more tolerable and so I would expect that this hopefully will be fairly widely adopted. Dr. Vamsi Velcheti: Yeah, I agree. I think this is a welcome change. Like, I think the infusion reactions and the resources it takes to get patients through treatments. I think it's definitely a win-win for patients and also the providers.  And with that, we come to the conclusion of the podcast. Nate, thank you so much for the fantastic insights today. Our listeners will find all the abstracts discussed today in the transcripts of the episode. Thank you so much for joining us today, Dr. Pennell.  Dr. Nate Pennell: Oh, thanks for inviting me. It's always fun to talk about all these exciting advances for our patients. Dr. Vamsi Velcheti: Thanks to our listeners for your time today. You will find links to all the abstracts discussed today in the transcript of the episode. Finally, if you value the insights that you hear from ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcast.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers:    Dr. Vamsi Velcheti  @VamsiVelcheti    Dr. Nathan Pennell  @n8pennell    Follow ASCO on social media:      @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:  Dr. Vamsi Velcheti:  Honoraria: ITeos Therapeutics  Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus  Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline  Dr. Nathan Pennell:    Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron   Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi

Send us a Text Message.Joseph Ferra is CEO of Elevation Oncology ( https://elevationoncology.com/ ), a clinical stage biopharmaceutical company focused on the development of precision oncology products, specifically antibody-drug-conjugates (ADCs), for patients with genomically defined cancers, where he brings over 20 years of financial, strategic and leadership experience in the pharmaceutical/biotechnology industry. Prior to becoming CEO, he served Elevation as Chief Financial Officer and Interim CEO. Before joining Elevation, Joseph was Chief Financial Officer of Syros Pharmaceuticals where he led the development and implementation of key financial and capital strategies and contributed to corporate initiatives. Previously, he spent over a decade as an investment banker in the biotechnology and pharmaceutical industry, where he established a strong track record of advising on equity and M&A transactions. This included serving as Managing Director and Co-Head of Healthcare Investment Banking at JMP Securities and being a member of the investment banking groups at JP Morgan and UBS. Earlier in his career, Joe served in sales and engineering roles in the life science tools industry. He earned his MBA from The Stephen M. Ross School of Business at the University of Michigan. He obtained a B.S. in Chemistry with Distinction from Purdue University, where he contributed to published papers and conducted research at the National Institutes of Health. Dr. David Dornan is Chief Scientific Officer of Elevation Oncology where he brings over two decades of industry and academic oncology drug discovery and development experience. His research spans across multiple therapeutic modalities targeting cancer susceptibilities and modulating the immune system to translate into meaningful therapeutic interventions for patients. He joins Elevation Oncology from Bolt Biotherapeutics. As Chief Scientific Officer, he was responsible for the scientific strategy and building of the company's portfolio in targeted immunotherapies. Prior to this, Dr. Dornan was the head of Oncology Research at Gilead, identifying, validating, and translating oncogenic targets into actionable entities with biologic and small molecule therapeutics and oversaw the integrated oncology strategy team. He began his career at Genentech, where he spent 10 years serving in positions of increasing responsibility and played key roles in target discovery and validation, as well as translational research programs. Dr. Dornan received his Ph.D. from the University of Dundee in Molecular Oncology and Biochemistry and completed a postdoctoral fellowship at Genentech. Support the Show.

Drs. Vamsi Velcheti and Nathan Pennell discuss key lung cancer abstracts from the 2024 ASCO Annual Meeting, including data from LUMINOSITY and ADAURA, novel therapies in KRASG12C-mutant advanced NSCLC, and the need for effective adjuvant therapies for patients with rare mutations. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I am Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I'm a professor of medicine and director of thoracic medical oncology at Perlmutter Cancer Center at NYU Langone Health. Today, I'm delighted to welcome Dr. Nathan Pennell, the co-director of the Cleveland Clinic Lung Cancer Program and vice chair of clinical research at the Taussig Cancer Center. Dr. Pennell is also the editor-in-chief of the ASCO Educational Book. Dr. Pennell is sharing his valuable insights today on key abstracts in lung cancer that will be presented at the 2024 ASCO Annual Meeting. You'll find our full disclosures in the transcript of the episode.  Nate, it's great to have you here on the podcast. Thank you for being here. Dr. Nathan Pennell: Thanks, Vamsi, for inviting me. I'm always excited for the ASCO Annual Meeting, and we have a tremendous amount of exciting lung cancer abstracts. I know we're not going to discuss all of them on this podcast, but even exciting Plenary presentations coming up.  Dr. Vamsi Velcheti: So, one of the abstracts that caught my attention was Abstract 103, the LUMINOSITY trial, which will be presenting the primary analysis at the meeting. So, there's a lot of buzz and excitement around ADCs. Can you comment on this abstract, Nate, and what are your thoughts on key takeaways from this abstract?  Dr. Nathan Pennell: Absolutely, I agree. This is really an exciting new potential target for lung cancer. So historically, when we think about MET and lung cancer, we think about the MET exon 14 skipping mutations which are present in 3% or 4% of adenocarcinoma patients. And we have approved tyrosine kinase inhibitors, small molecule inhibitors that can be very effective for those. What we're talking about here is actually an antibody drug conjugate or ADC telisotuzumab vedotin, which is targeting the MET protein over expression in non-squamous EGFR wild type advanced non-small cell lung cancer. The LUMINOSITY was a single arm, phase 2 study of teliso, and first of all, I think we have to define the patient population. So, these were MET over expressing non-small cell lung cancer by immunohistochemical staining. So, it included both what they considered MET high expression and MET intermediate expression, both of which had to be 3+ IHC positive on 25% to 50% of cells in the intermediate and 50% or higher in the high expressing group. They were treated with the ADC and had pretty promising results, a response rate of 35% in the MET high group and 23% in the intermediate group. Duration of response at nine months and 7.2 months in those two groups, and the PFS was five and a half and six months. So I would say in a previously treated population, this was relatively promising and potentially defines a completely new and unique subgroup of biomarker defined patients. So, Vamsi, I'm curious, though, if this ends up moving forward to further development, what your thoughts are on adding yet another biomarker in non-small cell lung cancer? Dr. Vamsi Velcheti: Yeah, I think it's certainly exciting. I think for this population, we really don't have a lot of options beyond the second line, and even in the second line, docetaxels are low bar. So,I think having more options for our patients is certainly outcome development. And I think MET IHC is relatively easy to deploy in a clinical setting. I think we already test for MET PD-L1 IHC routinely, and now recently, as you know, HER2 IHC given approval for ADCs, HER2 ADCs there in that space. So, I think from a technical standpoint, I don't see a big barrier in terms of adding an additional IHC marker. And usually, the IHC testing is pretty quick. And I think if you have a therapeutic approval based on IHC positivity, I think certainly from an operational standpoint, it shouldn't be a very complicated issue. Dr. Nathan Pennell: Yeah, I agree. This is cheap. It's something that can be done everywhere in the world. And as you said, in addition to diagnostic IHC, we're already looking at PD-L1, and probably moving towards doing that for HER2. This is really wonderful that we're moving into kind of the era of the ADCs, which is opening up a whole new therapeutic group of options for patients. Dr. Vamsi Velcheti: So, the other abstract that caught my attention was like, the Abstract 8005. This is the molecular residual disease MRD analysis from the ADAURA trial. The ADAURA trial, as you all know, is the trial that led to the FDA approval of adjuvant use of osimertinib in patients with EGFR mutant stage 1B through 3A non-small cell lung cancer. And in this trial, osimertinib demonstrated significant improvements in DFS and OS. And in this particular study, Abstract 8005, the authors looked at the role of MRD in predicting DFS in the study. And after 682 patients who were randomized, 36% of the patients had samples to look at MRD post- surgery. And in the trial the MRD status predicted DFS or event free survival at 36 months with a hazard ratio of 0.23. And the MRD status had a median lead time of 4.7 months across both the arms, both osimertinib and the placebo arm. So, suggesting that MRD could potentially identify high risk subgroups of patients post-surgery to tailor personalized approaches potentially in this population. So, Nate, in your practice, of course, we don't have a clinically validated approach yet to kind of use MRD in this setting, but if we have an option to use an MRD based assay, do you think that would potentially be an opportunity to perhaps escalate or de-escalate adjuvant strategies with TKIs in the adjuvant setting? Do you see value in using MRI assays post- surgery? Dr. Nathan Pennell: Yeah, I think this is a really important study because this is such an important topic around adjuvant targeted treatment. So, of course, ADAURA really changed how we treated people with EGFR mutant lung cancer who underwent surgical resection, because we know that the three years of osimertinib significantly improved disease-free survival and overall survival. But there's still a lot of questions being asked about, is that affordable? Obviously, we're putting a lot of resources into three years of treatment, and not everyone necessarily needs it. There may well be people who are cured with surgery alone and adjuvant chemotherapy. And then what about duration? Is three years enough? Do we need even longer treatment, or do we need shorter treatment? And up to date, we haven't really been able to tell people at risk of recurrence other than the pure odds-based risk based on their stage.   And the assay that was used in the ADAURA study was a personalized tumor informed assay based on the resected tumor. It's unclear to me whether this was just a subgroup of people that had this done or whether they tried to do it in all 600 patients and only, it looks like they were successful in about 32% of people. Maybe about a third were able to successfully have a tumor informed assay. So, the first question is, “Can you use this to help guide who needs treatment or not?” And I think what they showed was only about 4% of people in osimertinib arm in 12% had MRD positive at baseline after surgery. So probably, upfront testing is not really going to be all that helpful at determining who's at high risk and needs to be treated.   Interestingly, of those who were positive, though, most of them, or 80% of them, did go MRD negative on osimertinib. And what I found really interesting is that of those who did have a recurrence, 65% of them did have the MRD test turn positive. And as you mentioned, that was about five months prior to being picked up radiographically, and so you can pick them up sooner. And it also looks like about two thirds of recurrences can be identified with the blood test. So that potentially could identify people who are recurring earlier that might be eligible for a more intensive treatment. The other thing that was really interesting is of those who recurred in the osimertinib arm, 68% of them happened after stopping the osimertinib, suggesting that for the majority of patients, even those not necessarily cured, they seem to have disease control while on the osimertinib, suggesting that maybe a longer duration of treatment for those patients could be helpful. The problem is it still isn't necessarily helpful at identifying who those people are who need the longer duration of treatment. So, definitely an important study. I think it could be useful in practice if this was available clinically, especially at monitoring those after completion of treatment. I think as the sensitivity of these MRD assays gets better, these will become more and more important. Dr. Vamsi Velcheti: I think it's a little bit of a challenge in terms of standardizing these assays, and they're like multiple assays, which are currently commercially available. And I think the field is getting really complicated in terms of how you incorporate different assays and different therapeutics in the adjuvant space, especially if you're kind of looking at de-escalating immunotherapeutic strategies at the adjuvant setting, I think, makes it even more challenging. I think exciting times. We definitely need more thoughtful and better studies to really define the role of MRD in the adjuvant space. So, I guess more to come in this space. Dr. Nathan Pennell: Vamsi, I wanted to ask you about another really interesting Abstract 8011. This is a subgroup of the AEGEAN perioperative study for early-stage resected non-small cell lung cancer. This abstract is specifically looking at baseline N2 lymph node involvement in stage 2A-3B with N2 positive patients in an exploratory subgroup analysis. What are your key takeaways from the study?   Dr. Vamsi Velcheti: I felt this was a very interesting abstract for a couple of reasons. As you know, this is the AEGEAN trial, the phase 3 trial that was reported earlier last year. This is a perioperative study of durvalumab plus new adjuvant chemotherapy versus new adjuvant chemotherapy alone and adjuvant durvalumab plus placebo. The study obviously met its primary endpoint, as we all saw, like the event-free survival. And here in this abstract, the authors present an exploratory subgroup analysis of patients who had N2 lymph node involvement prior to study enrollment. So, in this study, they were focusing on perioperative outcomes. And one of the issues that has come up multiple times, as you know, in a lot of these preoperative studies, is the impact of neoadjuvant chemo immunotherapy on surgery or surgical outcomes. And consistently, across a lot of these trials, including the CheckMate 816, about 20% of patients don't end up making it to surgery. So in that light, I think this study and the findings are very interesting. In this study, they looked at patients who had N2 nodal involvement and of the patients with N2 nodal involvement, the surgical operability or the number of patients who completed surgery was similar in both the groups. So, there was no significant difference between patients who received durva versus chemotherapy and also among patients who had N2 subgroup who had surgery, similar proportions of durvalumab and placebo arms had open versus minimally invasive versus pneumonectomy. So durvalumab didn't have a negative impact on the type of surgery that the patients had at the time of surgery. So overall, the findings were consistent with other trials, perioperative trials that we have seen. So, the surgical outcomes were not negatively impacted by adding immunotherapy in the neoadjuvant perioperative space. So, this is consistent with other trials that we have seen. And also, the other issue, Nate, I'd like to get your opinion on is, across the board, in all the perioperative trials we have seen that about 20% of the patients actually don't end up making it a surgery. And of course, most of these perioperative trials, a lot of these patients are stage 3 patients. And my take on this was that there's probably a little bit of a patient selection issue. We generally tend to err on the side of operability when we have a stage 3 patient discussed in the tumor board, sometimes feel like the patient may downstage and could potentially go to surgery. But even in the real world, in stage 3 operable patients, what proportion of patients do you think don't end up going to surgery? Dr. Nathan Pennell: That is such an important question that I don't think we have the best answer to. You're right. All of these perioperative studies have a relatively high- sort of 20% to 30% of people who enroll on the studies don't necessarily go to surgery. And I don't think that they've done as great a job as they could in all of these trials describing exactly what happens to these patients. So in the real world, obviously not everyone would be fit enough to go to surgery or might progress in the time between when they were diagnosed and the time as planned for surgery. But probably more of them would go to surgery if they weren't getting neoadjuvant treatment, because that would be their initial treatment. The question is, of course, is that the right choice? If someone gets 12 weeks or nine weeks of neoadjuvant treatment and then a restaging scan shows that they've had progression with metastatic disease, are those really the people that would have been optimally treated with surgery upfront, or would they just have had recurrence on their first postoperative scan? So, it's really an important question to answer. I think the bigger one is, is the treatment preventing them through toxicity from going to treatment? And I think the studies have generally felt that few patients are missing out on the option of surgery because of toxicity being caused by the IO. And in the AEGEAN study, for example, in this subgroup, a slightly numerically higher percentage of patients in the durvalumab arm actually underwent surgery compared to those who got neoadjuvant chemo. So, it doesn't seem like we're necessarily harming people with the neoadjuvant treatment. But I know that this is a concern for patients and doctors who are undergoing this approach. Dr. Vamsi Velcheti: Definitely, I think having multiple data sets from perioperative trials, looking at the relative impact of IO on the safety and the nature of the surgery is going to be important, and this is a very important study for that reason. Dr. Nathan Pennell: Can I ask you another thing that I thought really interesting about this particular one is they looked at the difference between those with single station N2 and multi station N2. And I know this is one of those, should we be operating on people who have multi station N2 disease? And the AEGEAN study did include people who had multiple N2 stations where perhaps in the pre-IO era, these would have been treated with definitive chemoradiation and not surgery at all. But the disease-free survival hazard ratio was essentially the same for multi station N2 as it was in the overall population. So, has that changed the way we're approaching these patients in these multidisciplinary discussions? Dr. Vamsi Velcheti: Absolutely, Nate. I think surgical operability is in the eye of the beholder. I think it depends on which surgeon sees the patient or how the discussion goes in the tumor boards, as you know. Certainly, I think with this optionality of having a chemo IO option and potential for downstaging, kind of pushes, at least in our practice, more of these patients who are multistation, who would have otherwise gone down the chemoradiation route are now actually going through neo adjuvant chemo IO and with the hope that they would make it to surgery. So, I think it's an interesting change in paradigm in managing our locally advanced patients. So, I think it's certainly interesting, but I guess to your point, there clearly are some patients who probably should just have chemoradiation upfront, and we may be kind of like delaying that definitive chemoradiation approach for at least a subset of patients. So, at the end of the day, I think it's a lot of clinical decision-making and I think there's going to be a little bit of art to managing these patients and it's going to be really hard to define that population for a clinical trial.  Dr. Nathan Pennell: Yeah, clearly, multidisciplinary discussion, still very important for earliest age non-small cell lung cancer patients. If we move back to metastatic lung cancer, let's talk about Abstract 8510 looking at one of our newer, exciting biomarkers, which are the KRASG12Cmutant non-small cell lung cancer. So this is a study of a second generation KRASG12Cinhibitor, olomorasib, which was combined with pembrolizumab, the anti PD-1 antibody, in patients with advanced KRASG12C mutant non-small cell lung cancer. This is something that has been tried before with first generation G12C inhibitors, with some concerns about how safe it was to do that. So, Vamsi, what did you learn from this abstract? Dr. Vamsi Velcheti: Definitely, I think one of the concerns that we've had in other trials is like the cumulative toxicity of adding checkpoint inhibition to G12C inhibitors, especially the sotorasib CodeBreaK trial, where we see increased rates of grade 3, 4 transaminitis. So, it is encouraging to see that some of the newer agents have less of those issues when it comes to combining the checkpoint inhibition. So especially with KRASG12C, as you know, these are patients who are smokers, and often these are patients who have high PDL-1 could potentially also benefit from immunotherapy. In order for these KRASG12C inhibitors, in order to move these targeted therapy options for these patients to the front line, I do think we need to have substantial comfort in combining the checkpoint inhibitors, which is a standard treatment approach for patients in the frontline setting. I think this is exciting, and I think they're also like, as you know, there are other KRASG12C inhibitors also looking to combine with checkpoint inhibition in the frontline settings. So, we'll have to kind of wait and see how the other agents will perform in the setting. Dr. Nathan Pennell: Yeah, I completely agree. I think this is such an important area to explore specifically because unlike our other targeted oncogenes like EGFR and ALK, we have multiple options for these patients, both immunotherapy and targeted treatments. And if we could think about sequencing them or even combining them and if it could be done safely, I think that would be well worth investigating. There still was significant toxicity in this trial; 30% of people had diarrhea, even at the reduced dose, and there was transaminitis at sort of about 20% or so, although probably at a manageable level. But the response rate was really quite promising. And these are all previously IO and mostly G12C TKI pre-treated patients still had a response rate of 63%. And in those who were naive to IO and TKIs, it was 78% response rate. So, if it could be done safely, I think it's definitely worth pursuing this in further trials. Dr. Vamsi Velcheti: And also, there's some data, preclinical data, like looking at G12C inhibition. And also we have known with MET inhibition for a long time that it could potentially augment immune responses and could be having some synergistic effect with IO. So, we'll have to wait and see, I think. But safety is really the top in mind when it comes to combining these agents with checkpoint inhibitors. So, it's really encouraging to see that some of the newer agents may be more combinable IO. Now moving on to the next abstract, and moving on to, again, the early-stage setting. So, Abstract 8052 from our colleagues in Princess Margaret reported outcomes in early-stage non- small cell lung cancer in patients with rare targetable mutation. This is actually becoming increasingly more relevant because we are seeing at least, like with the ALINA data, with the ALK and EGFR, now with ADAURA, we know that these patients don't benefit with adjuvant immunotherapy, especially some of these rare oncogene living mutations, other than like G12C. So I always struggle with this. When you have early-stage patients, with, let's say, a ROS or a RET, where we just don't have data, and we know that those are poor actors because biologically these are aggressive tumors. So, there's a really odd clinical question to ask in terms of, what is the role of adjuvant immunotherapy? Of course, this trial and this abstract are not really addressing that. But what is your take on this abstract? If you could just summarize the abstract for us. Dr. Nathan Pennell: Sure. Well, I think this is incredibly important, and this is an area near and dear to my own heart. And that is, of course, the whole landscape of how we manage early-stage patients has changed with both ADAURA, because we now have effective treatment in the adjuvant setting for EGFR mutant patients, and now more recently with the ALINA trial for adjuvant alectinib for ALK positive patients now being FDA-approved. So, what that means is we actually have to be testing people at diagnosis even before they would be getting adjuvant treatment, and potentially before even surgery to look for these targets. We need the PD-L1 status, we need EGFR and ALK. And if you're going to be looking at these biomarkers, I think there is a reasonable argument to be made that you should be doing broad testing for all of the targetable oncogenes in these patients. There are some studies suggesting that there's value to this and identifying them for treatment at the time of recurrence. But we also know that these patients are at high risk of recurrence and probably need to be investigated, at least in trials for the adjuvant setting. So, this particular study looked at 201 resected, mostly adenocarcinoma patients, and then they basically sequenced them for all of the targeted oncogenes. And they were quite common, perhaps even more common than you might expect in an advanced population. So, 43% of them had KRASG12C mutations, 13% had EGFR Exon 20 mutation, ERBB2 or HER2 mutations found in 11%, MET mutations in 10%, ALK in 7%, ROS1 in 6%, BRAF in 5%, and RET in 2%. So quite common to find these targetable oncogenes in this particular population, perhaps a somewhat biased population at Princess Margaret Hospital, but very common. And then they looked at the outcomes of these patients without targeted adjuvant treatment. And what they found was there was a very high rate of recurrence. So, relapse-free survival was pretty high in these patients across different stages, and generally their prognosis was worse than the more common KRASG12C patients. Most of these, in particular the HER2 mutant patients, seem to have a significantly worse relapse free survival. Interestingly enough, though, that did not carry over to overall survival. Overall survival was better in those who had targetable oncogenes. And my guess is that that probably had to do with the availability of targeted treatments at the time of recurrence that may have impacted overall survival. But I do think that this particularly highlights the need, the unmet need for effective adjuvant treatment in these patients. And most of them, with the exception of KRAS and perhaps BRAF, perhaps MET unlikely to benefit from adjuvant immunotherapy, as you mentioned. And so, I think we really need to be investing in trials of adjuvant targeted treatments in these populations.  Dr. Vamsi Velcheti: Yeah, this is an area that we really don't have a lot of data. But Nate, a question for you. So tomorrow you have a patient with RET fusion, stage 2, N1 disease. What would you do? Would you offer them an adjuvant RET inhibitor? Dr. Nathan Pennell: I think I would search really hard for a trial to give them access. But if you really want to know what I think, and I'm usually willing to tell people what I think, I think the proof of concept is there. I think we know that in the setting of highly effective and very tolerable adjuvant targeted treatment in the EGFR space with osimertinib, in the ALK space with alectinib, if anything, drugs like selpercatinib and pralsetinib in RET fusion positive lung cancer in the advanced setting are just as well tolerated and easily as effective and long lasting. And so, I think if you did a trial and they are doing trials looking at these drugs in the adjuvant space, almost certainly you're going to see the same really dramatic disease-free survival benefit from these treatments, which, at least in the EGFR space, seems to have translated into an improvement in overall survival. And so if I had a stage II or a resected stage 3, especially a RET fusion positive patient today, I would definitely talk to them about off-label use of a RET inhibitor if I could not find a trial. Now, I understand that there are going to be reimbursement issues and whatnot associated with that, but I think the extrapolation is worth discussing. Dr. Vamsi Velcheti: Yeah, I think it's really challenging because some of these fusions are so rare and it's hard to really do large adjuvant trials for some of these rarer subgroups. Nate, fascinating insights. Our listeners will find links to the abstracts we discussed today in the transcript of the episode. And Nate, I look forward to catching up with you at the Annual Meeting, and again after the meeting for our wrap up podcast to discuss the practice-changing lung cancer abstracts and highlights from the Plenary Session. Thank you so much for joining us and sharing your insights today. Dr. Nathan Pennell: Thanks for inviting me. Vamsi. I look forward to touching base after we get to see all the late-breaking abstracts. Like I said, this is, I think, a year for lung cancer with a lot of exciting data, and I know we'll have a lot to talk about. Dr. Vamsi Velcheti And thank you so much to all our listeners for your time. If you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate and review and subscribe wherever you get your podcast.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's speakers: Dr. Vamsi Velcheti @VamsiVelcheti   Dr. Nathan Pennell @n8pennell   Follow ASCO on social media:   @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn     Disclosures: Dr. Vamsi Velcheti: Honoraria: ITeos Therapeutics Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline   Dr. Nathan Pennell:   Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron  Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi 

Doctors Vamsi Velcheti, Sandip Patel, and Michael Zervos discuss recent updates on the management of early-stage non-small cell lung cancer (NSCLC), including the optimization of neoadjuvant and adjuvant treatment options for patients and the role of surgery in the era of targeted therapy and immuno-oncology in lung cancer. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I am a professor of medicine and director of thoracic medical oncology at the Perlmutter Cancer Center at NYU Langone Health. On today's episode, we'll be discussing recent updates on the management of early-stage non-small cell lung cancer (NSCLC), including the optimization of neoadjuvant and adjuvant treatment options for our patients, and the evolving role of surgery in the era of targeted therapy and immuno-oncology in lung cancer.  Today, I am delighted to be joined by two renowned experts in this space, Dr. Sandip Patel and Dr. Michael Zervos. Dr. Patel is a professor of medicine and a medical oncologist specializing in lung cancer at UCSD. Dr. Mike Zervos is the clinical chief of the Division of Robotic Thoracic Surgery and Director of General Thoracic Surgery at NYU Langone. Our full disclosures are available in the transcript of this episode, and disclosures relating to all episodes of the podcast are available at asco.org/DNpod. Dr. Patel and Dr. Zervos, it's a great honor to have you on the podcast today. Welcome aboard. Dr. Sandip Patel: Great to be joining you.  Dr. Vamsi Velcheti:  Let's get started with Dr. Patel. As you know, over the last decade we've had dramatic advances in systemic therapy options for patients with metastatic non-small cell lung cancer, in both the realms of targeted therapy and immunotherapy. These have significantly improved outcomes for our patients with metastatic lung cancer. What's exciting is that more recently, we've seen the incorporation of these agents, both targeted therapies and immunotherapies, in early-stage non-small cell lung cancer. Dr. Patel, can you tell our listeners about these exciting recent advances and why do you think it's so important to incorporate these personalized systemic therapy options for our early-stage patients? Dr. Sandip Patel: I think it's a great point and a great question. And so, I think one thing to understand is that non-small cell lung cancer is actually multiple diseases. We give it one name based on how it looks under the microscope, but the vast majority of our advances to improve outcomes for patients have come from our ability to understand specific subgroups.  Many of our therapies have had activity in the advanced setting. We have our patients with metastatic or more widespread disease, which naturally led to the thought that could we utilize these therapies in earlier stage disease and potentially increase the rate of cure for many of our patients, lung cancer being the most common cancer killer worldwide. And so to your point, trying to understand how to best treat a patient really involves personalized medicine, typically driven by understanding the genomic profile of their tumor and two of the genes that have graduated from being tested for in the metastatic setting and now in the localized setting are EGFR and ALK. And these in particular are mutations that confer sensitivity to small molecule inhibitors, EGFR with osimertinib, ALK in the localized setting with alectinib based on the data that we've seen.  And so, one of the areas that's been particularly exciting is our ability to maximize a patient's chance for durable remissions by integrating these therapies after surgery, after chemotherapy when appropriate, and continuing generally for a finite amount of time, two to three years depending on the agent in the study we're discussing for these patients. Additionally, immunotherapy, which has revolutionized our treatment of patients with metastatic disease, may be particularly well-suited for the localized setting of non-small cell lung cancer as well. Dr. Vamsi Velcheti: Excellent points, Sandip. You're absolutely right, in the metastatic setting, we've all come to accept molecular testing, sequencing, and biomarker profiling as a standard, but unfortunately, that hasn't quite yet percolated into the early-stage setting. Can you talk about some of the challenges that we face as we have these therapeutic options available now for more early-stage patients? Dr. Sandip Patel: So, I think there are 3 flavors of localized therapy in non-small cell lung cancer. One is the advanced, unresectable stage 3, for which the approach is often concurrent chemo-radiation followed by some form of consolidated therapy. We're about to hear the results of LAURA, which is the study looking at EGFR-mutated non-small cell lung cancer.  For other patients, historically, the treatment has been durvalumab, an anti-PD-L1 directed immunotherapy. The other two are operative treatment of localized cancer: adjuvant treatment after surgery, or neoadjuvant or perioperative, in which chemoimmunotherapy begins before surgery. And testing depends on the settings. For the stage 3 patient who's likely getting concurrent chemo-radiation, they may have a very small amount of tissue, and so often these are done by pulmonary EBUS biopsies and that's how we pathologically confirm that advanced stage 3B. There may not be a lot of tissue available for molecular testing. In fact, if you look at the PACIFIC analysis, just looking at PD-L1, which is just an IHC off a single slide, a third of patients weren't able to even get a PD-L1, let alone a genomic result. And so, I think that's one of the areas of LAURA that's going to be particularly interesting to see as we try to implement it into our practice after seeing the full data.  I think in the adjuvant setting, we're lucky because our surgeons, Dr. Mike Zervos here, will get us a large amount of tissue in the surgical resection specimen, so we tend to get enough tissue to do genomics while they're under chemotherapy, there tends to be time to wait for their genomic result. Where this really gets complicated is in the neoadjuvant or perioperative setting, where time is everything.  The most important thing we can do for a patient in the localized space is get them to the operating room, get them started on radiation, their curative local modality, and that's where we have a time pressure but also a sample pressure because that is a diagnostic biopsy. It's a very small piece of tissue. Initially, there are multiple stains that have to be done to identify this lung cancer as opposed to another tumor. And so that's an area that I think we're going to need additional approaches given that cell-free DNA tends to have lower yield in lower stage disease in giving us a result. Dr. Vamsi Velcheti: Great points, Sandip. How do you deal with this issue in San Diego? The challenge is now we have a lot of trials, we'll talk about those neoadjuvant immunotherapy trials, but we know that immunotherapy may not be as effective in all patients, especially those with EGFR or ALK or some of these non-smoker, oncogene-driven tumors. So, we don't want to be giving patients treatments that may not necessarily be effective in the neoadjuvant space, especially when there is a time crunch, and we want to get them to surgery and all the complications that come with giving them targeted therapy post-IO with potential risk for adverse events. Dr. Sandip Patel: Absolutely. It is a great point. And so, the multidisciplinary team approach is key, and having a close relationship with the interventional pulmonary oncs, interventional radiology surgery, and radiation oncology to ensure that we get the best treatment for our patients. With the molecularly guided therapies, they are currently more on the adjuvant setting in terms of actually treating. But as you mentioned, when we're making a decision around neoadjuvant or perioperative chemo IO, it's actually the absence of EGFR now that we're looking for because our intervention at the current time is to give chemoimmunotherapy. Going back to the future, we used to use single gene EGFR within 24 hours, which was insufficient for a metastatic panel, but it often required five slides of tissue input. ALK can be done by IHC, and so some of these ‘oldie but goodie' pathologic techniques, and that pathologists, if I haven't emphasized, understanding what we're trying to do at a different context is so key because they are the ones who really hold the result. In the neoadjuvant and perioperative setting, which many of us favor, especially for stage 3A and stage 2B disease, understanding how we can get that result so that we can get the patient to the operating room in an expeditious way is so important. There is a time pressure that we always had in the metastatic setting, but I think we feel much more acutely in the neoadjuvant and perioperative setting in my opinion. Dr. Vamsi Velcheti: Fascinating insights, Dr. Patel.  Turning to Dr. Zervos, from a surgical perspective, there has been an evolution in terms of minimally invasive techniques, robotic approaches, and enhanced recovery protocols, significantly improving outcomes in our patients post-surgery. How do you see the role of surgery evolving, especially with the increasing complexity and efficacy of these systemic therapies? How do you envision the role of surgery in managing these early-stage patients, and what are the key considerations for surgeons in this new era? Dr. Michael Zervos: Thanks, Vamsi. Thanks, Sandip. Thank you for having me on the podcast. Obviously, it's an honor to be a part of such a high-level discussion. I have to say, from a surgeon's perspective, we often listen to you guys talk and realize that there's been a lot of change in this landscape. And I think the thing that I've seen is that the paradigm here has also changed. If we were having this discussion 10 years ago, a lot of the patients that I am operating on now, I would not be operating on. It really has been amazing. And I think the thing that stands out to me the most is how all of this has changed with neoadjuvant chemotherapy checkpoint inhibition. I think, for us as surgeons, that's really been the key. Whether it's CheckMate 816 or whatever you're following, like PACIFIC, the data supports this. And I think what we're seeing is that we're able to do the surgery, we're able to do it safely, and I think that the resectability rates are definitely high up there in the 90% range. And what we're seeing is pretty significant pathologic responses, which I think is really amazing to me.  We're also seeing that this has now shifted over to the oligometastatic realm, and a lot of those patients are also being treated similarly and then getting surgery, which is something that we would not have even thought of ever. When you look at the trials, I think a lot of the surgery, up to this point, has been done more traditionally. There's a specific reason why that happens, specifically, more through thoracotomy, less with VATS, and less with robotic. Sandip, I think you guys have a pretty robust robotic program at UCSD, so I'm sure you're pretty used to seeing that.   As you guys have become so much more sophisticated with the treatments, we have also had to modify what we do operatively to be able to step up to the plate and accept that challenge. But what we are seeing is yes, these treatments work, but the surgeries are slightly more complicated. And when I say slightly, I'm minimizing that a little bit.  And what's complicated about it is that the treatment effect is that the chemo-immune check inhibition actually has a significant response to the tumor antigen, which is the tumor. So it's going to necrose it, it's going to fibrose it, and wherever there is a tumor, that response on the surgical baseline level is going to be significant. In other words, there are going to be lymph nodes that are stuck to the pulmonary artery, lymph nodes that are stuck to the airway, and we've had to modify our approaches to be able to address that.   Now, fortunately, we've been able to innovate and use the existing technology to our advantage. Personally, I think robotics is the way we have progressed with all this, and we are doing these surgeries robotically, mainly because I think it is allowing us, not only to visualize things better, but to have sort of a better understanding of what we're looking at. And for that matter, we are able to do a better lymph node dissection, which is usually the key with a lot of these more complicated surgeries, and then really venturing out into more complicated things, like controlling the pulmonary artery. How do we address all this without having significant complications or injuries during the surgery? Getting these patients through after they've successfully completed their neoadjuvant treatment, getting them to surgery, doing the surgery successfully, and hopefully, with minimal to no morbidity, because at the end, they may be going on to further adjuvant treatment. All of these things I think are super important. I think although it has changed the landscape of how we think of things, it has made it slightly more complicated, but we are up for the challenge. I am definitely excited about all of this. Dr. Vamsi Velcheti: For some reason, like medical oncologists, we only get fixated on the drugs and how much better we're doing, but we don't really talk much about the advances in surgery and the advances in terms of outcomes, like post-op mortality has gone down significantly, especially in larger tertiary care centers. So, our way of thinking, traditionally, the whole intergroup trials, the whole paradigm of pneumonectomies being bad and bad outcomes overall, I think we can't judge and decide on current treatment standards based on surgical standards from decades ago. And I think that's really important to recognize.  Dr. Michael Zervos: All of this stuff has really changed over the past 10 years, and I think technology has helped us evolve over time. And as the science has evolved for you with the clinical trials, the technology has evolved for us to be able to compensate for that and to be able to deal with that. The data is real for this. Personally, what I'm seeing is that the data is better for this than it was for the old intergroup trials. We're able to do the surgery in a better, more efficient, and safer way. The majority of these surgeries for this are not going to be pneumonectomies, they are going to be mostly lobectomies. I think that makes sense. I think for the surgeons who might be listening, it doesn't really matter how you're actually doing these operations. I think if you don't have a very extensive minimally invasive or robotic experience, doing the surgery as open is fine, as long as you're doing the surgery safely and doing it to the standard that you might expect with complete lymph node clearance, mediastinal lymph node clearance, and intrapulmonary lymph node clearance. Really, I think that's where we have to sort of drive home the point, really less about the actual approach, even though our bias is to do it robotically because we feel it's less morbidity for the patient. The patients will recover faster from the treatment and then be able to go on to the next phase treatments. Dr. Vamsi Velcheti: In some of the pre-operative trials, the neoadjuvant trials, there have been some concerns raised about 20% of patients not being able to make it to surgery after induction chemo immunotherapy. Can you comment on that, and why do you think that is the case, Sandip?  Dr. Sandip Patel: Well, I think there are multiple reasons. If you look, about half due to progression of disease, which they might not have been great operative candidates to begin with, because they would have early progression afterwards. And some small minority in a given study, maybe 1% to 2%, it's an immune-related adverse event that's severe. So, it's something that we definitely need to think about. The flip side of that coin, only about 2 in 3 patients get adjuvant therapy, whether it be chemotherapy, immunotherapy, or targeted therapy. And so, our goal is to deliver a full multimodal package, where, of course, the local therapy is hugely important, but also many of these other molecular or immunologically guided agents have a substantial impact.  And I do think the point around neoadjuvant and perioperative is well taken. I think this is a discussion we have to have with our patients. I think, in particular, when you look at higher stage disease, like stage 3A, for example, the risk-benefit calculus of giving therapy upfront given the really phenomenal outcomes we have seen, really frankly starting with the NADIM study, CheckMate816, now moving on into studies like KEYNOTE-671, AEGEAN, it really opens your eyes in stage 3. Now, for someone who's stage 1/1b, is this a patient who's eager to get a tumor out? Is there as much of an impact when we give neoadjuvant therapy, especially if they're not going to respond and may progress from stage 1 and beyond? I think that's a reasonable concern. How to handle stage II is very heterogeneous. I think two points that kind of happen as you give neoadjuvant therapy, especially chemo-IO that I think is worth for folks to understand and this goes to Mike's earlier point, that is this concept if they do get a scan during your neoadjuvant chemo immunotherapy, there is a chance of that nodal flare, where the lymph nodes actually look worse and look like their disease is progressing. Their primary tumor may be smaller or maybe the same. But when we actually go to the OR, those lymph nodes are chock-full of immune cells. There's actually no cancer in those lymph nodes. And so that's a bit of a red herring to watch out for.   And so, I think as we're learning together how to deliver these therapies, because the curative-intent modality is, in my opinion, a local modality. It's what Mike does in the OR, my colleagues here do in the OR. My goal is to maximize the chance of that or really maximize the long-term cure rates. And we know, even as long as the surgery can go, if only 2 or 3 patients are going to get adjuvant therapy then 1 in 10, of which half of those or 1 in 20, are not getting the surgery and that's, of course, a big problem. It's a concern. I think better selecting towards those patients and thinking about how to make these choices is going to be hugely important as we go over. Because in a clinical trial, it's a very selective population. A real-world use of these treatments is different. I think one cautionary tale is that we don't have an approval for the use of neoadjuvant or perioperative therapy for conversion therapy, meaning, someone who's “borderline resectable.” At the time at which you meet the patient, they will be resectable at that moment. That's where our best evidence is, at the current time, for neoadjuvant or perioperative approaches.  Dr. Vamsi Velcheti:   I think the other major issue is like the optimal sequencing of immune checkpoint here. Obviously, at this point, we have multiple different trial readouts, and there are some options that patients can have just neoadjuvant without any adjuvant. Still, we have to figure out how to de-escalate post-surgery immunotherapy interventions. And I think there's a lot of work that needs to be done, and you're certainly involved in some of those exciting clinical trials. What do you do right now in your current clinical practice when you have patients who have a complete pathologic response to neoadjuvant immunotherapy? What is the discussion you have with your patients at that point? Do they need more immunotherapy, or are you ready to de-escalate?  Dr. Sandip Patel: I think MRD-based technologies, cell-free DNA technologies will hopefully help us guide this. Right now, we are flying blind along two axes. One is we don't actually know the contribution of the post-operative component for patients who get preoperative chemo-IO. And so this is actually going to be an ongoing discussion. And for a patient with a pCR, we know the outcomes are really quite good based on CheckMate816, which is a pure neoadjuvant or front-end only approach. Where I actually struggle is where patients who maybe have 50% tumor killing. If a patient has only 10% tumor killing ... the analogy I think in clinic is a traffic light, so the green light if you got a pCR, a yellow light if you have that anywhere from 20%-70% residual viable tumor, and then anything greater than that, you didn't get that much with chemo-IO and you're wondering if getting more chemo-IO, what would that actually do? It's a bit of a red light. And I'm curious, we don't have any data, but my guess would be the benefit of the post-op IO is because patients are in that kind of yellow light zone. So maybe a couple more cycles, we'll get them an even more durable response. But I am curious if we're going to start relying more on MRD-based technologies to define treatment duration. But I think it's a very complicated problem. I think folks want to balance toxicity, both medical and financial, with delivering a curative-intent therapy. And I am curious if this maybe, as we're looking at some of the data, some of the reasons around preferring a perioperative approach where you scale it back, as opposed to a neoadjuvant-only approach where there's not a clean way to add on therapy, if you think that makes sense. But it's probably the most complicated discussions we have in clinic and the discussion around a non-pCR. And frankly, even the tumor board discussions around localized non-small cell lung cancer have gone very complex, for the benefit of our patients, though we just don't have clean data to say this is the right path.   Dr. Vamsi Velcheti: I think that the need for a really true multidisciplinary approach and discussing these patients in the tumor board has never been more significant. Large academic centers, we have the luxury of having all the expertise on hand. How do we scale this approach to the broader community is a big challenge, I think, especially in early-stage patients. Of course, not everyone can travel to Dr. Zervos or you for care at a large tertiary cancer centers. So, I think there needs to be a lot of effort in terms of trying to educate community surgeons, community oncologists on managing these patients. I think it's going to be a challenge. Dr. Michael Zervos: If I could just add one thing here, and I completely agree with everything that has been said. I think the challenge is knowing beforehand. Could you predict which patients are going to have a complete response? And for that matter, say, “Okay. Well, this one has a complete response. Do we necessarily need to operate on this patient?” And that's really the big question that I add. I personally have seen some complete response, but what I'm mostly seeing is major pathologic response, not necessarily CR, but we are seeing more and more CR, I do have to say. The question is how are you going to predict that? Is looking for minimal residual disease after treatment going to be the way to do that? If you guys could speak to that, I think that is just tremendously interesting.  Dr. Vamsi Velcheti: I think as Sandip said, MRD is looking very promising, but I just want to caution that it's not ready for primetime clinical decision making yet. I am really excited about the MRD approach of selecting patients for de-escalation or escalation and surgery or no surgery. I think this is probably not quite there yet in terms of surgery or no surgery decision. Especially for patients who have early-stage cancer, we talk about curative-intent treatment here and surgery is a curative treatment, and not going to surgery is going to be a heavy lift. And I don't think we're anywhere close to that. Yet, I'm glad that we are having those discussions, but I think it may be too hard at this point based on the available technologies to kind of predict CR. We're not there.  Dr. Michael Zervos: Can I ask you guys what your thought process is for evaluating the patient? So, when you're actually thinking about, “Hey, this patient actually had a good response. I'm going to ask the surgeons to come and take a look at this.” What imaging studies are you actually using? Are you just using strictly CT or are you looking for the PET? Should we also be thinking about restaging a lot of these patients? Because obviously, one of the things that I hate as a surgeon is getting into the operating room only to find out that I have multiple nodal stations that are positive. Which really, in my opinion, that's sort of a red flag. And for me, if I have that, I'm thinking more along the lines of not completing that surgery because I'm concerned about not being able to provide an R0 resection or even having surgical staple lines within proximity of cancer, which is not going to be good. It's going to be fraught with complications.  So, a lot of the things that we as surgeons struggle with have to do with this. Personally, I like to evaluate the patients with an IV intravenous CT scan to get a better idea of the nodal involvement, proximity to major blood vessels, and potentially even a PET scan. And though I think in this day and age, a lot of the patients will get the PET beforehand, not necessarily get it approved afterwards. So that's a challenge. And then the one thing I do have to say that I definitely have found helpful is, if there's any question, doing the restaging or the re-EBUS at that point to be particularly helpful.  Dr. Sandip Patel: Yeah, I would concur that having that pathologic nodal assessment is probably one of the most important things we can do for our patients. For a patient with multinodal positive disease, the honest truth is that at our tumor board, that patient is probably going to get definitive chemoradiation followed by their immunotherapy, or potentially soon, if they have an EGFR mutation, osimertinib. For those patients who are clean in the mediastinum and then potentially have nodal flare, oftentimes what our surgeons will do as the first stage of the operation, they'll actually have the EBUS repeated during that same anesthesia session and then go straight into surgery. And so far the vast majority of those patients have proceeded to go to surgery because all we found are immune cells in those lymph nodes.  So, I think it's a great point that it's really the pathologic staging that's driving this and having a close relationship with our pathologists is key. But I think one point that I think we all could agree on is the way that we're going to find more of these patients to help and cure with these therapies is through improved utilization of low-dose CT screening in the appropriate population in primary care. And so, getting buy-in from our primary care doctors so that they can do the appropriate low-dose CT screening along with smoking cessation, and find these patients so that we can offer them these therapies, I think is something that we really, as a community, need to advocate on. Because a lot of what we do with next-generation therapies, at least on the medical oncology side, is kind of preaching to the choir. But getting the buy-in so we can find more of these cases at stage 1, 2 or 3, as opposed to stage 4, I think, is one of the ways we can really make a positive impact for patients. Dr. Vamsi Velcheti: I just want to go back to Mike's point about the nodal, especially for those with nodal multistation disease. In my opinion, those anatomic unresectability is a moving target, especially with evolving, improving systemic therapy options. The utilization for chemo radiation has actually gone down. I think that's a different clinical subgroup that we need to kind of think differently in terms of how we do the next iteration or generation of clinical trials, are they really benefiting from chemo-IO induction? And maybe we can get a subset of those patients in surgery. I personally think surgery is probably a more optimal, higher yield to potentially cure these patients versus chemo radiation. But I think how we identify those patients is a big challenge. And maybe we should do a sequential approach induction chemo-IO with the intent to kind of restage them for surgery. And if they don't, they go to chemo consolidation radiation, I guess. So, I think we need to rethink our approach to those anatomically unresectable stage 3s. But I think it's fascinating that we're having these discussions. You know, we've come to accept chemo radiation as a gold standard, but now we're kind of challenging those assumptions, and I think that means we're really doing well in terms of systemic therapy options for our patients to drive increased cures for these patients. Dr. Michael Zervos: I think from my perspective as a surgeon, if I'm looking at a CT scan and trying to evaluate whether a patient is resectable or not, one of the things that I'm looking for is the extent of the tumor, proximity to mediastinal invasion, lymph nodes size. But if that particular patient is resectable upfront, then usually, that patient that receives induction chemo checkpoint inhibition is going to be resectable afterwards. The ones that are harder are the ones that are borderline resectable upfront or not resectable. And then you're trying to figure out on the back end whether you can actually do the surgery.  Fortunately, we're not really taking many patients to the operating room under those circumstances to find that they're not resectable. Having said that, I did have one of those cases recently where I got in there and there were multiple lymph node stations that were positive. And I have to say that the CT really underestimated the extent of disease that I saw in the operating room. So, there are some challenges surrounding all of these things. Dr. Sandip Patel: Absolutely. And I think for those patients, if upfront identification by EBUS showed multi nodal involvement, we've had excellent outcomes by working with radiation oncologists using modern radiotherapy techniques, with concurrent chemo radiation, followed by their immunotherapy, more targeted therapy, at least it looks like soon. I think finding the right path for the patient is so key, and I think getting that mediastinal pathologic assessment, as opposed to just guessing based on what the PET CT looks like, is so important. If you look at some of the series, 8% to 10% of patients will get a false-positive PET on their mediastinal lymph nodes due to coccidioidomycosis or sarcoidosis or various other things. And the flip side is there's a false-negative rate as well. I think Mike summarized that as well, so I think imaging is helpful, but for me, imaging is really just pointing the target at where we need to get pathologic sampling, most commonly by EBUS. And getting our interventional pulmonary colleagues to help us do that, I think is so important because we have really nice therapeutic options, whether it's curative-intent surgery, curative-intent chemo radiation, where we as medical oncologists can really contribute to that curative-intent local therapy, in my opinion.  Dr. Vamsi Velcheti: Thank you so much Sandip and Mike, it's been an amazing and insightful discussion, with a really dynamic interplay between systemic therapy and surgical innovations. These are really exciting times for our patients and for us. Thank you so much for sharing your expertise and insights with us today on the ASCO Daily News Podcast.   I want to also thank our listeners today for your time. If you value the insights that you hear today, please take a moment to rate, review, and subscribe to the podcast wherever you get your podcasts. Thank you so much. [FH1]   Dr. Sandip Patel: Thank you. Dr. Michael Zervos: 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. Vamsidhar Velcheti @VamsiVelcheti Dr. Sandip Patel @PatelOncology Dr. Michael Zervos   Follow ASCO on social media: @ASCO on X (formerly Twitter) ASCO on Facebook ASCO on LinkedIn   Disclosures:  Dr. Vamsidhar Velcheti: Honoraria: ITeos Therapeutics Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline   Dr. Sandip Patel: Consulting or Advisory Role: Lilly, Novartis, Bristol-Myers Squibb, AstraZeneca/MedImmune, Nektar, Compugen, Illumina, Amgen, Certis, Eli Lilly, Roche/Genentech, Merck, Pfizer, Tempus, Iovance Biotherapeutics. Speakers' Bureau: Merck, Boehringer Ingelheim Research Funding (Inst.):Rubius, Bristol-Myers Squibb, Pfizer, Roche/Genentech, Amgen AstraZenece/MedImmune, Fate, Merck, Iovance, Takeda   Dr. Michael Zervos: No relationships to disclose

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

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

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

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

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

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

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

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

Relatively new CEO Joseph Ferra has orchestrated some pretty significant change at Elevation Oncology in the two(ish) years since the Business of Biotech last hosted the company.  In that short time, Ferra advance from CFO to CEO, a move that aligned very closely with the company's difficult decision to shelve the late phase 2 anti-HER3 monoclonal antibody candidate it was founded on. Those big moves set the stage for Elevations' new lead candidate, a phase 1 Claudin18.2 target in the oh-so-hot ADC (antibody drug conjugate) space.  On this episode of the Business of Biotech, we go behind the scenes to learn why and how those daring moves were made, and how Elevation navigated the gauntlet of risk it assumed when it embraced disruption in a not-so-shiny biotech market. 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!

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/YXT865. CME/MOC/AAPA credit will be available until January 2, 2025.Under Pressure to Improve: How to Unlock the Power of Antibody–Drug Conjugates to Transform the Treatment of Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and 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; Merck & Co., Inc.; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Pfizer; and Sanofi.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 Medicines Corporation; Boehringer Ingelheim Pharmaceuticals, Inc.; Celgene Corporation; Daiichi Sankyo Inc./AstraZeneca; Eisai Inc.; Genentech, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer; Regeneron Pharmaceuticals Inc./sanofi-aventis U.S. LLC; and Turning Point Therapeutics, Inc.Grant/Research Support from AstraZeneca/MedImmune; Genentech, Inc./F. Hoffmann-La Roche Ltd; Incyte; MacroGenics, Inc.; and Merck Sharp & Dohme LLC.Faculty/PlannerRebecca S. Heist, MD, MPH, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Claim Therapeutics; Daiichi Sankyo, Inc.; EMD Serono Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; and Sanofi.Grant/Research Support from AbbVie Inc.; Daiichi Sankyo, Inc.; Erasca, Inc.; Lilly; Mirati Therapeutics, Inc.; Mythic Therapeutics; Novartis Pharmaceuticals Corporation; Symphogen; and Turning Point Therapeutics, Inc. All to institution.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Data Safety Monitoring Board for Candel 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.

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/YXT865. CME/MOC/AAPA credit will be available until January 2, 2025.Under Pressure to Improve: How to Unlock the Power of Antibody–Drug Conjugates to Transform the Treatment of Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and 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; Merck & Co., Inc.; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Pfizer; and Sanofi.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 Medicines Corporation; Boehringer Ingelheim Pharmaceuticals, Inc.; Celgene Corporation; Daiichi Sankyo Inc./AstraZeneca; Eisai Inc.; Genentech, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer; Regeneron Pharmaceuticals Inc./sanofi-aventis U.S. LLC; and Turning Point Therapeutics, Inc.Grant/Research Support from AstraZeneca/MedImmune; Genentech, Inc./F. Hoffmann-La Roche Ltd; Incyte; MacroGenics, Inc.; and Merck Sharp & Dohme LLC.Faculty/PlannerRebecca S. Heist, MD, MPH, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Claim Therapeutics; Daiichi Sankyo, Inc.; EMD Serono Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; and Sanofi.Grant/Research Support from AbbVie Inc.; Daiichi Sankyo, Inc.; Erasca, Inc.; Lilly; Mirati Therapeutics, Inc.; Mythic Therapeutics; Novartis Pharmaceuticals Corporation; Symphogen; and Turning Point Therapeutics, Inc. All to institution.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Data Safety Monitoring Board for Candel 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.

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/YXT865. CME/MOC/AAPA credit will be available until January 2, 2025.Under Pressure to Improve: How to Unlock the Power of Antibody–Drug Conjugates to Transform the Treatment of Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and 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; Merck & Co., Inc.; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Pfizer; and Sanofi.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 Medicines Corporation; Boehringer Ingelheim Pharmaceuticals, Inc.; Celgene Corporation; Daiichi Sankyo Inc./AstraZeneca; Eisai Inc.; Genentech, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer; Regeneron Pharmaceuticals Inc./sanofi-aventis U.S. LLC; and Turning Point Therapeutics, Inc.Grant/Research Support from AstraZeneca/MedImmune; Genentech, Inc./F. Hoffmann-La Roche Ltd; Incyte; MacroGenics, Inc.; and Merck Sharp & Dohme LLC.Faculty/PlannerRebecca S. Heist, MD, MPH, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Claim Therapeutics; Daiichi Sankyo, Inc.; EMD Serono Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; and Sanofi.Grant/Research Support from AbbVie Inc.; Daiichi Sankyo, Inc.; Erasca, Inc.; Lilly; Mirati Therapeutics, Inc.; Mythic Therapeutics; Novartis Pharmaceuticals Corporation; Symphogen; and Turning Point Therapeutics, Inc. All to institution.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Data Safety Monitoring Board for Candel 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.

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/YXT865. CME/MOC/AAPA credit will be available until January 2, 2025.Under Pressure to Improve: How to Unlock the Power of Antibody–Drug Conjugates to Transform the Treatment of Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and 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; Merck & Co., Inc.; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Pfizer; and Sanofi.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 Medicines Corporation; Boehringer Ingelheim Pharmaceuticals, Inc.; Celgene Corporation; Daiichi Sankyo Inc./AstraZeneca; Eisai Inc.; Genentech, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer; Regeneron Pharmaceuticals Inc./sanofi-aventis U.S. LLC; and Turning Point Therapeutics, Inc.Grant/Research Support from AstraZeneca/MedImmune; Genentech, Inc./F. Hoffmann-La Roche Ltd; Incyte; MacroGenics, Inc.; and Merck Sharp & Dohme LLC.Faculty/PlannerRebecca S. Heist, MD, MPH, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Claim Therapeutics; Daiichi Sankyo, Inc.; EMD Serono Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; and Sanofi.Grant/Research Support from AbbVie Inc.; Daiichi Sankyo, Inc.; Erasca, Inc.; Lilly; Mirati Therapeutics, Inc.; Mythic Therapeutics; Novartis Pharmaceuticals Corporation; Symphogen; and Turning Point Therapeutics, Inc. All to institution.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Data Safety Monitoring Board for Candel 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.

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/YXT865. CME/MOC/AAPA credit will be available until January 2, 2025.Under Pressure to Improve: How to Unlock the Power of Antibody–Drug Conjugates to Transform the Treatment of Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and 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; Merck & Co., Inc.; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Pfizer; and Sanofi.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 Medicines Corporation; Boehringer Ingelheim Pharmaceuticals, Inc.; Celgene Corporation; Daiichi Sankyo Inc./AstraZeneca; Eisai Inc.; Genentech, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer; Regeneron Pharmaceuticals Inc./sanofi-aventis U.S. LLC; and Turning Point Therapeutics, Inc.Grant/Research Support from AstraZeneca/MedImmune; Genentech, Inc./F. Hoffmann-La Roche Ltd; Incyte; MacroGenics, Inc.; and Merck Sharp & Dohme LLC.Faculty/PlannerRebecca S. Heist, MD, MPH, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Claim Therapeutics; Daiichi Sankyo, Inc.; EMD Serono Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; and Sanofi.Grant/Research Support from AbbVie Inc.; Daiichi Sankyo, Inc.; Erasca, Inc.; Lilly; Mirati Therapeutics, Inc.; Mythic Therapeutics; Novartis Pharmaceuticals Corporation; Symphogen; and Turning Point Therapeutics, Inc. All to institution.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Data Safety Monitoring Board for Candel 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.

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/YXT865. CME/MOC/AAPA credit will be available until January 2, 2025.Under Pressure to Improve: How to Unlock the Power of Antibody–Drug Conjugates to Transform the Treatment of Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and 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; Merck & Co., Inc.; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Pfizer; and Sanofi.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 Medicines Corporation; Boehringer Ingelheim Pharmaceuticals, Inc.; Celgene Corporation; Daiichi Sankyo Inc./AstraZeneca; Eisai Inc.; Genentech, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer; Regeneron Pharmaceuticals Inc./sanofi-aventis U.S. LLC; and Turning Point Therapeutics, Inc.Grant/Research Support from AstraZeneca/MedImmune; Genentech, Inc./F. Hoffmann-La Roche Ltd; Incyte; MacroGenics, Inc.; and Merck Sharp & Dohme LLC.Faculty/PlannerRebecca S. Heist, MD, MPH, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Claim Therapeutics; Daiichi Sankyo, Inc.; EMD Serono Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; and Sanofi.Grant/Research Support from AbbVie Inc.; Daiichi Sankyo, Inc.; Erasca, Inc.; Lilly; Mirati Therapeutics, Inc.; Mythic Therapeutics; Novartis Pharmaceuticals Corporation; Symphogen; and Turning Point Therapeutics, Inc. All to institution.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Data Safety Monitoring Board for Candel 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.

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/YXT865. CME/MOC/AAPA credit will be available until January 2, 2025.Under Pressure to Improve: How to Unlock the Power of Antibody–Drug Conjugates to Transform the Treatment of Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and 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; Merck & Co., Inc.; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Pfizer; and Sanofi.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 Medicines Corporation; Boehringer Ingelheim Pharmaceuticals, Inc.; Celgene Corporation; Daiichi Sankyo Inc./AstraZeneca; Eisai Inc.; Genentech, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer; Regeneron Pharmaceuticals Inc./sanofi-aventis U.S. LLC; and Turning Point Therapeutics, Inc.Grant/Research Support from AstraZeneca/MedImmune; Genentech, Inc./F. Hoffmann-La Roche Ltd; Incyte; MacroGenics, Inc.; and Merck Sharp & Dohme LLC.Faculty/PlannerRebecca S. Heist, MD, MPH, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Claim Therapeutics; Daiichi Sankyo, Inc.; EMD Serono Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; and Sanofi.Grant/Research Support from AbbVie Inc.; Daiichi Sankyo, Inc.; Erasca, Inc.; Lilly; Mirati Therapeutics, Inc.; Mythic Therapeutics; Novartis Pharmaceuticals Corporation; Symphogen; and Turning Point Therapeutics, Inc. All to institution.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Data Safety Monitoring Board for Candel 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.

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/YXT865. CME/MOC/AAPA credit will be available until January 2, 2025.Under Pressure to Improve: How to Unlock the Power of Antibody–Drug Conjugates to Transform the Treatment of Lung Cancer In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and 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; Merck & Co., Inc.; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Pfizer; and Sanofi.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 Medicines Corporation; Boehringer Ingelheim Pharmaceuticals, Inc.; Celgene Corporation; Daiichi Sankyo Inc./AstraZeneca; Eisai Inc.; Genentech, Inc.; Janssen Pharmaceuticals, Inc.; Lilly; Merck & Co., Inc.; Pfizer; Regeneron Pharmaceuticals Inc./sanofi-aventis U.S. LLC; and Turning Point Therapeutics, Inc.Grant/Research Support from AstraZeneca/MedImmune; Genentech, Inc./F. Hoffmann-La Roche Ltd; Incyte; MacroGenics, Inc.; and Merck Sharp & Dohme LLC.Faculty/PlannerRebecca S. Heist, MD, MPH, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; AstraZeneca; Claim Therapeutics; Daiichi Sankyo, Inc.; EMD Serono Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; and Sanofi.Grant/Research Support from AbbVie Inc.; Daiichi Sankyo, Inc.; Erasca, Inc.; Lilly; Mirati Therapeutics, Inc.; Mythic Therapeutics; Novartis Pharmaceuticals Corporation; Symphogen; and Turning Point Therapeutics, Inc. All to institution.Faculty/PlannerStephen V. Liu, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AbbVie Inc.; Amgen Inc.; AstraZeneca; Boehringer Ingelheim International GmbH; Bristol Myers Squibb; Catalyst Pharmaceuticals Inc.; Daiichi Sankyo, Inc.; Eisai Inc.; Elevation Oncology, Inc.; F. Hoffmann-La Roche Ltd/Genentech, Inc.; Gilead Sciences, Inc.; Guardant Health; Janssen Pharmaceuticals, Inc.; Jazz Pharmaceuticals, Inc.; Merck & Co., Inc.; Merus; Mirati Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals Inc.; Sanofi; Takeda Pharmaceutical Company Limited; and Turning Point Therapeutics, Inc.Grant/Research Support from AbbVie Inc.; Alkermes; Elevation Oncology, Inc.; Ellipses; Genentech, Inc.; Gilead Sciences, Inc.; Merck & Co., Inc.; Merus; Nuvalent; RAPT Therapeutics; and Turning Point Therapeutics, Inc.Data Safety Monitoring Board for Candel 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.

About this episode: David Dornan is the Chief Scientific Officer of Elevation Oncology, a clinical-stage biotech company developing targeted cancer therapeutics, with a focus on antibody drug conjugates. David brings to Elevation over two decades of industry and academic oncology drug discovery and development experience. His research spans multiple therapeutic modalities targeting cancer susceptibilities and modulating the immune system to translate into meaningful therapeutic interventions for patients. As Chief Scientific Officer, he is responsible for scientific strategy and building of the company's portfolio in targeted immunotherapies. Before leading these efforts at Elevation Oncology, David was the CSO at Bolt Biotherapeutics. Prior to this, he was the head of Oncology Research at Gilead. David began his career at Genentech, where he spent 10 years serving in positions of increasing responsibility and played key roles in target discovery and validation, as well as translational research programs.David received his Ph.D. from the University of Dundee in Molecular Oncology and Biochemistry and completed a postdoctoral fellowship at Genentech. In this episode, we discuss Elevation's ongoing clinical development of antibody-drug conjugate molecules to treat cancer and David's wealth of experience in biotech and pharma.Hosted by Joe Varriale.

Drs. Vamsi Velcheti, Taofeek Owonikoko, and Janakiraman Subramanian discuss their experiences navigating the cancer drug shortage in the United States, the impact on patients and clinical trial enrollment, lessons learned, and proactive strategies to mitigate future crises. TRANSCRIPT  Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I'm a professor of medicine and director of thoracic oncology at the Perlmutter Cancer Center at NYU Langone. On today's episode, we'll be discussing the impact of the shortage of cancer chemotherapy drugs across the United States. This has been affecting several thousands of patients with adult and pediatric cancers and hampering enrollment in clinical trials. Among the shortages are very commonly used drugs like cisplatin, carboplatin, methotrexate, and fludarabine. Some of these shortages have persisted since the time of the pandemic in 2020.   So today, to discuss this really troubling scenario, I have two outstanding colleagues, Dr. Janakiraman Subramanian, the director of thoracic oncology at Inova Schar Cancer Institute in Virginia, and Dr. Taofeek Owonikoko, a professor of medicine and the chief of the Division of Hematology and Oncology at the University of Pittsburgh Hillman Cancer Center in Pittsburgh.   Our full disclosures are available in the transcript of this episode, and disclosures relating to all episodes of the podcast are available at asco.org/DNpod.  So, a recent survey by the NCCN found that 90% of the nation's largest cancer centers have experienced a shortage in carboplatin, and 70% of the centers have reported a shortage in cisplatin. These are platinum-based chemotherapies we use frequently in patients with cancer, and these are often curative intent treatments for several cancers, and these are used in several tumor types, both solid tumors and hematologic malignancies. So, the scale of the problem is immense.   Dr. Owonikoko, I'd like to hear your take on this situation and how are you dealing with this at the UPMC Cancer Center.  Dr. Taofeek Owonikoko: Yeah, thank you, Dr. Velcheti, and happy to be part of this panel. As you rightly surmised, the chemotherapy drug shortage is what we've all experienced across the length and breadth of the United States. Our cancer center here in Pittsburgh is not an exception. We've had to be proactive as well as think outside the box to be able to manage the challenge. Just like every other cancer center across the country, maybe to varying degrees, we've had to look at patients in need of chemotherapy with these standard-of-care agents such as cisplatin or carboplatin, and to some degree docetaxel, during this past episode of drug shortage that we all went through. And while we did not have to, fortunately, cancel any patient treatment, we all went through it with bated breath; not sure of where the next batch of chemotherapy drugs will come through, but I would say in the past couple of weeks, we've actually seen some improvement in drug availability.   But before then, we've had to have contingency plans where, on a weekly basis, we review our patient list and the drug regimens that they're going to need, and must make sure that we have enough drug on hand for those patients. And in situations where we thought we might not have enough drug; we also had a plan to use alternative regimens. We were proactive in having guiding principles that are consistent with ASCO's recommendations in terms of quality care delivery for cancer patients. So, I'm sure that this is more or less the same approach adopted by other leading cancer centers across the country.   Dr. Vamsi Velcheti: Thank you, Dr. Owonikoko. And Dr. Subramanian, you're in a community setting, a large cancer center that serves a lot of patients in the state of Virginia. So, what is the scale of the problem at your institution and how are you handling it?   Dr. Janakiraman Subramanian: First of all, Dr. Velcheti, thanks for having me here on this panel. And as you rightly said, this is a significant problem, and it is across the country like Dr. Owonikoko said. And as medical oncologists, we are not always thinking of drug shortages. Our focus is on taking care of our patients. So, this is one more issue that we need to keep in mind now as we manage our patients with cancer. When this shortage started, the biggest problem, as you know, was when we became aware of this was primarily in cisplatin and we had some of our patients who were getting curative treatment and we had to make a decision - can they get cisplatin or can they get carboplatin. And one of the things we did was to have an ethics committee that will review each patient that is being planned to receive cisplatin-based chemotherapy and come to a decision on how best we can support them.   The template for some of this was based upon some of the triage mechanisms we used during COVID, as well as the ASCO guideline document for managing this chemotherapy shortage, which was one of the blueprints we used. And they have reviewed all cases, all patients that are being planned for cisplatin or carboplatin for that matter, and we come to a decision based on that. And we also have another committee that constantly monitors drug availability on a weekly basis and tries to forecast where the next problem would be as we take care of our patients.   And particularly as a lung cancer doctor, we've had situations where we had to use carboplatin instead of cisplatin and even we also have carboplatin shortage. And so, the committee usually approves two cycles at a time, but thankfully so far we have not had a situation where we could not offer our patients the chemotherapy treatment. But we are very carefully monitoring the situation, hoping that this will improve.   The other aspect of the shortage has been in 5FU. A lot of our GI colleagues; I treat esophageal cancer patients as well, where we've had to forego the bolus 5FU and have a 10% reduction on all 5FU infusions. And we've been using some of that dose reduction to ensure that we can have 5FU available for all our patients. And that's how we've been trying to manage this shortage situation here at Inova Schar.   Dr. Vamsi Velcheti: Dr. Subramanian and Dr. Owonikoko, we are oncologists, we are treating patients, and the toughest part really is telling a patient that we don't have access to certain drugs and we have to switch treatments to perhaps another treatment regimen that may be suboptimal. And it's always a very anxiety-provoking discussion, and especially for patients with metastatic cancer, they're already under a lot of stress and it's a really difficult conversation. How do you handle that, Dr. Owonikoko?  Dr. Taofeek Owonikoko: That's a conversation we all hope we don't have to have. And fortunately, with this current crisis, I've actually not had such misfortune of having to inform a patient that we don't have drugs to treat them or that we have to switch to something inferior. But conceptually, it's possible that could have happened and that would have been very difficult. But the one thing that we did, though, as part of our mitigation strategy was actually to inform the patient ahead of time because the way we handled this was to look at our inventory on a week-by-week basis. And if there are patients where we felt maybe they will be coming in towards the end of the week and we may not have enough drugs for them, to let them know the possibility exists that we might have to switch them to something different. While we did not have to do that for any patient, yes, there are patients that we had to give that heads up to, to say, “We're having this shortage. We're doing everything we can to make sure it's available. But just in case it's not available…” I think what is most important for most patients is to be aware of that decision ahead of time, to be able to process it, and to be transparent.   The other challenge that we face was, if you have to choose between patients, what should be your guiding principles as to who gets the drug and who doesn't get it? I think it's very easy for all of us to say, “Oh, if it's curative intent, we do it. If it's not curative intent, we don't do it.” It's a little more complicated than that because if we put the equity hat on, curative intent doesn't actually mean that that life is more valuable than somebody who cannot be cured. And this is where really, I think having people with expertise in ethics of care delivery and disaster management will be very important for us to proactively anticipate that, should this become a recurrent problem in the future that we actually have a well-vetted approach, just like we did during COVID where you have to ration resources that we have those people with expertise to help us as oncologists because not all of us, at least personally I can speak for myself, that is not my area of expertise and comfort.  Dr. Vamsi Velcheti: Excellent points. Dr. Subramanian, anything to add?  Dr. Janakiraman Subramanian: Oh, absolutely. I echo what Dr. Owonikoko said. These are conversations that we would like to hopefully never have with our patients. But this is a crisis that we are facing now. And personally, I can tell you two situations where we ran into this problem. But overall, though, we never had to stop a treatment or cancel a treatment for our patient. In the first situation, we had a young man with a rare germ cell tumor in the hospital for whom cisplatin was key. He was already in the ICU and sometimes the treatment start dates are not perfect, unlike what we do in the outpatient setting, depending on how well he's doing or the treatment start dates might move by a day or so. So we basically had to hold a certain dose of cisplatin for him.   This brings the next question, which is how do we decide who gets cisplatin versus who can go for an alternative option? And I think Dr. Owonikoko made a great point where, just because it is a curative disease does not mean their life is more valuable. This is where I think trying to make that decision at an individual level, as an individual treating physician can be extremely hard. And that's why at our institution we have this ethics committee where we have oncologists, pharmacists, and ethicists that review these chemotherapy orders, particularly for cisplatin, and try to use some guiding principles that we learned from COVID as well as ASCO's guidance to decide how we assign our resources. That's one option, one way we have done it.    And then in another situation that was faced by one of my GI oncology colleagues was a patient that was originally planned to go on a clinical trial where the chemotherapy backbone was FOLFOX and because we had the 5FU shortage, we could not offer that patient clinical trial enrollment. And that was a tough conversation where they had to tell them that they could not go on a clinical trial that they were looking forward to. And this then brings the next question, which is by foregoing the bolus 5FU and by the 10% reduction in the infusional 5FU, are we providing them inferior treatment? And it's a conversation that's had at a very individual level. I don't envy my colleague who had to have that conversation. It's a challenge and we try to do our best to communicate to our patients that we are trying to provide care without trying to compromise the effectiveness of treatment for them.  Dr. Vamsi Velcheti: Thank you so much both of you. And we had the same issues here at NYU in New York City as well. It appears, you know, the degree of shortage and the drugs that are in shortage has been somewhat different at different locations across the United States. But the theme has been that we are having to ration treatments for our patients. And of course, there are some tumor types where there's really no adequate substitution, for example, GU cancers. I mean, you can't really not give them cisplatin. A lot of these are situations which have curative intent and young patients. So, it's really troubling.   And I think one of the things that really came out of this is there's been a lot of push from professional societies that actually ASCO has been spearheading and some intense discussions with CMS and legislators to kind of provide more long-term fix for these things. And I think all of us have to be more engaged in those discussions with our professional societies like ASCO to kind of help promote awareness. So if you kind of think about it, these drugs are not that expensive. These are generic drugs that we've all been using for such a long time. And the fact that we can't provide these drugs for various reasons is kind of really concerning. We spend so much money on research and more expensive drugs and not being able to manufacture these drugs within the country and kind of having to rely on complex supply chains is troubling, and I hope the situation improves very soon.    So, I know both of you are at large cancer centers that enroll patients on clinical trials. Of course, these drugs, especially carboplatin, for lung cancer, especially, are like core treatments that are used in managing cancer patients with lung cancer. So how is this affecting your clinical trial accrual? Are you prioritizing patients on clinical trials for these drugs? Have you had to make any decisions to hold clinical trial accrual for certain trials? Kind of curious to hear.  Dr. Taofeek Owonikoko: Yeah, so I can maybe weigh in a little bit on that in terms of what we've had to do for patients receiving treatment as standard of care versus those going on clinical trials. As we all recognize that when a patient goes on a clinical trial, even if they are going to receive a standard-of-care regimen as part of that trial, it still has to be administered in line with the protocol. So, during the extreme period of shortage anxiety, we actually had consideration for perhaps not putting patients on trial if we're not sure that they will be able to continue to receive the protocol-mandated treatment, whether it's a control intervention or the experimental intervention.   The good thing to come out of this is at least here at UPMC, we actually did not have any instance where we had to deny a patient clinical trial participation. But there were anxious periods when we already had patients enrolled and they were scheduled to receive a platinum-containing regimen and we were not sure whether or not we were going to have adequate supply of the drug for them while on trial. I think this really raises an important consideration going forward as we come out of this current shortage. I don't by any stretch of the imagination assume that this is going to be the last one we experience, but I think the lessons learned here, we have to also carry that forward both in the design of the trial as well as in the regulatory environment surrounding clinical trial conduct, to say, should another incidence of drug shortage are to happen, how do we actually operationalize that with respect to patients on trial, whether starting or already on trial?   I think it's much more challenging when the patient is already on the trial, they've already started. It's less challenging if you just have to make a decision about somebody starting newly on the trial. But equally important is that by not allowing new patients to go on trial is denying something that potentially could be of benefit to them, albeit it is still a trial, it's not an established treatment option yet.  Dr. Janakiraman Subramanian : I completely agree with Dr. Owonikoko. Those were very key points and issues that we face as well. In terms of my patients with lung cancer, we haven't had a problem in getting them on clinical trials. Even though we have had carboplatin shortage patients who are already on treatment, they were able to get the carboplatin. For new patients, we were still able to provide them carboplatin as well. The biggest problem for clinical trials has been primarily with my GI colleagues who have to use 5FU. And there, as I said before, we are unable to give bolus 5FU and there is a 10% reduction of the infusional 5FU. So, we can't have any of these patients go on clinical trials.    And as a result, anything that has to do with 5FU has come to a screeching halt in terms of clinical trials for our patients. And I think I echo the point of Dr. Owonikoko that by no means this is the last drug shortage we're going to be dealing with and we are here today discussing this, also because this shortage has not ended. It's been ongoing. It's one of the longest drug shortages in my memory as a medical oncologist, and that's concerning. We still see that there is some improvement, but we haven't gotten past it yet.     And therefore, as we develop clinical trials and we need to have methods to address drug shortages and how we manage patient enrollment as well as how do we manage existing patients who are already on a clinical trial and, if possible, what might be their options in that situation. We may not have all the answers, but it is definitely an issue that we need to think about in the future as we develop and implement newer clinical trials for our patients.  Dr. Vamsi Velcheti: I completely agree and great points, both of you. And we've had the same issues with clinical trials at NYU Langone as well due to the shortage. It's been a challenge, and I think this is a problem that's so complex because of supply chain issues and the way the drugs are priced and incentives for manufacturing these drugs in the United States are not lucrative enough to actually onshore a lot of the production of these drugs.   I think at the end of the day, I think we have to come up with some creative, innovative, reimbursement structures for these generic chemotherapy drugs. I think this would require a very complex economic solution that perhaps ASCO and other organizations should kind of really foster an environment of innovation to kind of help facilitate onshoring some of the manufacturing of these key drugs within the United States. I think ASCO is already trying to do that, trying to collaborate with all the stakeholders to kind of address this problem is very critical, and I think all of us have to be engaged in some of the advocacy efforts that are ongoing to kind of address these drug shortages. And this is not a short-term problem.  So, Dr. Owonikoko and Dr. Subramanian, any final thoughts before we wrap up the podcast today?  Dr. Janakiraman Subramanian: So, Vamsi, you mentioned the whole complex supply chain and the fact that we rely primarily on overseas manufacturers to get these drugs that are off-patent but still a key backbone of our cancer treatment. I think those are all key issues that policymakers and leaders in the field have to keep in mind. As an institution at Inova, one of the key mechanisms that have helped us to sort of stay ahead of the shortage was to have this inventory management team that monitors the inventory out there. And in fact, the inventory management team does have access to what the inventory is in some of their main suppliers in terms of the drugs. And they also have an idea of how many patients are going through treatment, what is the weekly usage of a specific drug like carboplatin. And they try to forecast what is coming down the road and try to prepare for it.   And as we try to look for solutions, maybe a forecasting mechanism in a larger scale like either spearheaded by ASCO or by policymakers level that can, for the overall country, try to see where some of the inventory is for some of these critical drugs and try to prepare for it ahead of time, rather than wait till we hit the shortage and then try to find alternative suppliers to get the drug, which obviously doesn't happen quick enough. It takes months or even longer to catch up and get the inventory back to the level where we can comfortably take care of our patients.  I think that is something we should be advocating for that as well as the professional societies should take a handle on that and see if they can support something like that as well as letting the institutions know ahead of time what's coming might be very helpful.  Dr. Vamsi Velcheti: Yeah, very good point, Janakiraman, and I think that's a key takeaway here. I think we have to learn from other industries and try to– I mean this is not unique to healthcare by any means. I mean these chronic shortages due to supply chain issues, inventory management, there might be some learnings from other industries here that we probably should also focus on inventory management and improve supply chain logistics.   Dr. Owonikoko, any closing thoughts?   Dr. Taofeek Owonikoko: Yeah, I agree as well with all the points made by Dr. Subramanian and yourself. This is a chronic problem that requires a long-term strategy. I think it's both an economic problem as well as a regulatory problem. As we all know, part of the reason why we went through this current crisis is the regulatory decision by the FDA regarding safety of one of the manufacturers. So being proactive in terms of how these audits are conducted and giving people lead time I think will help avoid similar situations in the future.    It's an economic problem. There's a reason why a lot of the big pharma companies are not producing these drugs. And if the cost of production is such that the amount of money you get paid is enough to cover your price, I think there is an economic issue there to be addressed. That is unfortunately not within the scope of what any one of us can do individually, but as advocates in terms of the structure of incentivizing new drug versus old drug, some of these newer drugs are quite expensive, but oftentimes they are used along with standard drugs that are not as expensive. So, where do we strike that balance where we do not stifle innovation but at the same time, we don't create a perverse incentive system where everybody just wants to come up with the newest, most expensive drug and nobody is interested in really producing the backbone chemotherapy and other agents that will make those new drugs work well.   So, I think we have to pay attention. We have to advocate for our patients through our different institutions and organizations, and I hope that society as a whole that we've learned a lot of lessons from this crisis and that will help us craft some long-term strategies.   Dr. Vamsi Velcheti: Thank you both Dr. Owonikoko and Dr. Subramanian for your time today to speak with me and our listeners and for sharing your insights with us on the ASCO Daily News podcast.   Dr. Taofeek Owonikoko: Thank you.   Dr. Janakiraman Subramanian: Thank you.  Dr. Vamsi Velcheti: And thank you to our listeners for your time today. If you value the insights that you hear on ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcast. Thank you so much.  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.  ASCO Resources Related to Drug Shortages are available here.     Follow today's speakers:    Dr. Vamsidhar Velcheti    @VamsiVelcheti    Dr. Janakiraman Subramanian  @RamSubraMD  Dr. Taofeek Owonikoko  @teekayowo    Follow ASCO on social media:     @ASCO on X (formerly Twitter)    ASCO on Facebook    ASCO on LinkedIn      Disclosures:     Dr. Vamsidhar Velcheti:     Honoraria: ITeos Therapeutics    Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus    Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline      Dr. Janakiraman Subramanian:  Consulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, Daichi, G1 Therapeutics, Jazz Pharmaceuticals, Janssen Oncology, Lilly, Blueprint Medicines, Axcess, BeiGene, Cardinal Health, Takeda, OncoCyte  Speakers' Bureau: AstraZeneca, Boehringer Ingelheim, G1 Therapeutics, Jazz Pharmaceuticals, Janssen Oncology  Research Funding (Inst.): G1 Therapeutics, Tesaro/GSK, Novartis, Genentech, Novocure, Merck   Dr. Taofeek Owonikoko:  Stocks and Other Ownership Interests: Cambium Oncology, GenCart, Coherus Biosciences  Consulting or Advisory Role: Novartis, Celgene, Abbvie, Eisai, GI Therapeutics, Takeda, Bristol-Myers Squibb, MedImmune, BerGenBio, Lilly, Amgen, AstraZeneca, PharmaMar, Boehringer Ingelheim, EMD Serono, Xcovery, Bayer, Merck, Jazz Pharmaceuticals, Zentalis, Wells Fargo, Ipsen, Roche/Genentech, Janssen, Exelixis, BeiGene, Triptych Health Partners, Daichi, Coherus Biosciences  Speakers Bureau: Abbvie  Research Funding (Inst.): Novartis, Astellas Pharma, Bayer, Regeneron, AstraZenece/MedImmune, Abbvie, G1Therapeutics, Bristol-Myers Squibb, United Therapeutics, Amgen, Loxo/Lilly, Fujifilm, Pfizer, Aeglea Biotherapeutics, Incyte, Merck, Oncorus, Ispen, GlaxoSmithKline, Calithera Biosciences, Eisai, WindMIL, Turning Point Therapeutics, Roche/Genentech, Mersana, Meryx, Boehringer Ingelheim  Patents, Royalties, Other Intellectual Property (Inst.):   Overcoming Acquired Resistance to Chemotherapy Treatments Through Suppression of STAT3  Selective Chemotherapy Treatments and Diagnostic Methods Related Thereto  DR4 Modulation and Its Implications in EGFR-Target Cancer Therapy Ref: 18089 PROV (CSP) United States Patent Application No. 62/670,210 June 26, 2018 (Co-Inventor)  Soluble FAS ligand as a biomarker of recurrence in thyroid cancer; provisional patent 61/727,519 (Inventor)  Other Relationship: Roche/Genentech, EMD Serono, Novartis  Uncompensated Relationships: Reflexion Medical           

Drs. Vamsi Velcheti and Jack West discuss ADAURA, KEYNOTE-671, and KEYNOTE-789 trials in NSCLC and the first pivotal study of sunvozertinib for the treatment of NSCLC with EGFR exon 20 insertion mutations. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast. I'm a professor of medicine and director of thoracic medical oncology at the Perlmutter Cancer Center at NYU Langone Health. My guest today is Dr. Jack West, a thoracic oncologist and associate professor in medical oncology at City of Hope Comprehensive Cancer Center. Today, we'll be discussing practice-changing studies and other key advances in lung cancer that were featured at the 2023 ASCO Annual Meeting.   Our full disclosures are available in the transcript of this episode and disclosures of all guests on the ASCO Daily News podcast are available at asco.org/DNpod.   Jack, there was a lot of exciting new data that emerged from the ASCO Annual Meeting, and it's great to have you back on our podcast today to talk about all the key updates in lung cancer.   Dr. Jack West: Absolutely. Thanks so much. It's always a high-energy meeting, and there was a lot to talk about in the lung cancer sessions this year for sure.  Dr. Vamsi Velcheti: Let's begin with LBA3, the ADAURA trial. This was presented in the Plenary Session at ASCO; we've heard previously the DFS updates from previous meetings, and overall survival updates were presented at the ASCO 2023 Annual Meeting. So, Jack, what was the highlight of the presentation for you? And could you put things in context for us? We have known about the DFS data for a while now. What gets you so excited about this study?  Dr. Jack West: Well, we've actually been focused on this trial for literally 3 years, since Dr. Herbst presented it at another Plenary presentation back in the ASCO Meeting in 2020 when we saw tremendous differences in the DFS data. Again, this was a trial of patients with resected stage 1b to 3a EGFR mutation-positive non-small cell lung cancer. Nearly 700 patients were randomized to after-surgery, and for many, but not all, patients undergoing chemotherapy, it wasn't mandated. But after that, they were randomized to get adjuvant, placebo, or osimertinib for up to 3 years. And we saw huge differences in the disease-free survival from the first presentation, with a hazard ratio in the range of 0.2.   We have notably seen significant improvements in disease-free survival before with other EGFR TKIs for this population after surgery, but nothing in this range. And it's also notable that in the various other trials of other EGFR inhibitors in the postoperative setting, we've seen a DFS benefit, but that didn't translate to an improvement in overall survival. So, seeing a press release that this was associated with a significant and, in fact, highly significant by report, improvement in overall survival, as well as DFS, was really notable.   What's also, I think, particularly important as a focus of this is that in the later presentations of this work, with longer follow-up last year, we saw that the DFS curves showed a drop in the DFS starting after these patients had completed 3 years of treatment. So, really suggesting that at least some, if not many or most of these patients who had been on adjuvant osimertinib were subject to a higher risk of relapse once they completed that. So, again, making the endpoint of overall survival particularly important. It's always been to me the endpoint we should care about most in a curative setting. Although the DFS was the primary endpoint of the study and it was powered and built around specifically focusing on the DFS difference, so overall survival was reassuring, I think, when we actually saw it, but not what the trial was centered around.    And what we saw was a very dramatic improvement in overall survival with a hazard ratio of 0.49. That was essentially the same for the patients with stage 2 to 3a disease, as well as the broader population with stage 1b to 3a disease. When we look at the absolute numbers for overall survival at 5 years, there was an improvement from 73% to 85% with osimertinib, and in the population from 1b to 3a, an improvement from 78% to 88%. So, many things to comment on here. Really remarkable to see an 88% 5-year survival in the osimertinib arm that includes patients with stage 3a disease.    I would say that there's still some controversy, some questions about this, and it really centers around a few things. One is, like many global trials, this one enrolled patients from many places that did not have the same standard of care staging that we follow in the U.S. There wasn't any specification or mandate for PET scans, which would be very routine in the U.S. And brain MRIs were not mandated either. And so there were almost certainly some patients with more advanced disease that was not detected that would be a big advantage for the osimertinib arm, but really not characterized. And also, the crossover was made possible to osimertinib starting in April of 2020, but only 38.5% of the patients on the control arm actually received osimertinib at the time of relapse. And even though many of the other patients who had a relapse did get another EGFR inhibitor, I don't think there's much question that osimertinib is the preferred and optimal EGFR TKI.   And so there were a couple of important factors kind of going for this trial. One is the long, long, long duration of treatment at 3 years, though with a drop-off, I think some questions about whether even that is enough, and we might be tempted to treat beyond 3 years. And then how much did the inability of most of the patients on the control arm to get osimertinib later contribute? My personal view is that it is a troubling aspect of this trial. But also so many other trials that they're run globally in places where we arguably perpetuate these disparities by running these trials that, in part, magnify the differences between the two arms because some patients just will not have access to what is our best standard of care in the U.S., or many other parts of the world, but weren't necessarily available to many of the patients on the control arm where it was conducted. So, I think that's always a concern. It's definitely an issue of this trial, but I would not say it's unique to this one.  Dr. Vamsi Velcheti: Very good points, Jack, and I completely agree with you. I think those certainly are concerns. But on the other hand, this is a pragmatic trial and that's the real-world scenario in terms of access issues, in terms of osimertinib globally, correct, in the stage 4 setting, even though we all agree that osimertinib is the best option for patients with metastatic EGFR-mutated lung cancer, I think that's obviously a reflection of global access issues and global disparities and changes in standard of care in terms of workup as well. So, it's somewhat of a pragmatic trial in some ways and I completely agree with you, I think that may have potentially had some impact on the overall survival.  Dr. Jack West: Well, I would clarify that I don't think that this really highly significant difference in overall survival is undermined completely by this. There's no question in my mind that with the huge difference in disease-free survival that we'd already seen for 3 years, it has become our standard of care really for this population at least to offer it, if not to strongly recommend it. But I would say that most of us have been quite inclined to recommend it, perhaps with caveats. And I would say that this overall survival benefit mostly corroborates that, even if there are some concerns about how these trials are done, but it's still an impressive difference that would lead me to only cement my practice of pursuing it in this setting. I just would love to re-examine how we conduct these trials and potentially potentiate disparities that exist and don't want to have our trials be more positive by capitalizing on that.   Dr. Vamsi Velcheti: Let's move on to the next abstract, LBA100; this is the KEYNOTE-671 trial. This was featured during the meeting's Clinical Science Symposium. This is a study of pembrolizumab or placebo plus platinum doublet followed by surgical resection and pembrolizumab or placebo for early-stage non-small cell lung cancer. Jack, what was the key message from this trial, and do you consider this as practice-changing?  Dr. Jack West: This has been an area where we've seen really dramatic evolution in our practice patterns, specifically, at least for patients who don't have a tumor harboring an EGFR mutation or ALK rearrangement. I would say that there has been some momentum toward preoperative neoadjuvant therapy, specifically based on the CheckMate-816 trial that gave chemo with nivolumab versus placebo and showed a significant improvement in the pathologic complete response rate at surgery as well as event-free survival. The overall survival looks encouraging but is still early and hasn't met the threshold for statistical significance, and that's FDA-approved.   But we still question whether there's a value to doing anything in the postoperative setting. And the CheckMate-816 trial did not include that as part of the trial. It allowed postoperative management at the judgment of the treating physician but didn't really prescribe anything. We now have the results of several trials in the last few months that have added a component in the postoperative setting in addition to three or four cycles of preoperative chemoimmunotherapy. And the first one that gave us a glimpse was the AEGEAN trial presented by Dr. John Heymach at AACR in April of this year that looked at chemo and durvalumab versus chemo placebo and then followed by a year of durvalumab versus placebo after surgery. That showed results in terms of major pathologic response and event-free survival that are significantly better with immunotherapy. Not clearly superior to what we would see with CheckMate-816.   And then even more recently, we saw a monthly Plenary presentation from ASCO with the Neotorch trial presented by Dr. Shun Lu of China. This was a Chinese trial only that presented results just for patients with stage 3 disease thus far. This included patients with stage 2 or stage 3, but what we saw is stage 3 results and that looked at chemo with toripalimab for 3 cycles versus placebo and then a year of checkpoint inhibitor or placebo. This also shows a benefit with the addition of immunotherapy, but not clear if that's better than what we can already achieve with neoadjuvant alone with the Checkmate-816 approach.   And then what we have now is a presentation and simultaneous publication by Dr. Heather Wakelee of KEYNOTE-671. And this is really almost the exact same trial design as AEGEAN. It's 4 cycles of platinum doublet chemotherapy and it is for patients with stage 2 to 3a disease. And this gave 4 cycles of chemotherapy with placebo or pembrolizumab. And then after surgery, patients would go on in the investigation arm to a year of pembrolizumab or to the additional year with placebo. And this shows a significant improvement in event-free survival with a hazard ratio of 0.58. It's most prominent in patients with high PD-L1, where the hazard ratio is 0.42. But there's still a benefit in patients with PD-L1 less than 1%, where it's 0.77. And there was a trend toward better overall survival here, hazard ratio of 0.73. It does not reach statistical significance at this early point. It's still preliminary but certainly looks encouraging. And there are also significant improvements in major pathologic response, where less than 10%, about a threefold difference from 30.2% with immunotherapy compared to 11% with placebo. And a very impressive improvement in pCR rate, which is 18.1% with the chemo and pembro compared to 4% with chemotherapy alone. Not surprisingly, when we look at event-free survival, it's best in the patients who achieve a pathologic complete response, but pembrolizumab improved outcomes in event-free survival even for those who didn't achieve a pCR.   The real question I would say is does the addition of a year of checkpoint inhibitor therapy postoperatively add to what we already achieve with those first three cycles with chemo-neo or 4 cycles with maybe one of these other options? And these trials can't answer that question because they just include them as a package deal. There's no way to tease apart right now the component of what incremental benefits you get from that. And it certainly adds a year of time coming in for every 3-week infusions. Even if you space that out, it's still a year of coming in and getting infusions, potential cumulative immune-related toxicities, and a lot of cost versus potentially being done. And I think that really is the big question at this point of do you want to recommend something when we don't really have a precedent for much benefit beyond the first 4 cycles? Perhaps. Certainly, we give maintenance pemetrexed and other immunotherapies and there can be benefit there. So, I wouldn't say you necessarily cap that. But if there is resistant disease after the first 4 cycles you've already given 3 cycles, how much benefit is there? How likely is it that you're going to eradicate the last cancer cells with more?   That said, I think many patients, and oncologists myself perhaps included, are going to be inclined to err on the side of possibly over-treating, but at least trying to give everything that is part of a widely studied, FDA-approved approach once these options become available. I just think it's going to end up as a careful discussion with each patient about whether they'd prefer to just say they're done or do that extra year and really feel that even if it comes back, they've done everything that made sense to try.  Dr. Vamsi Velcheti: Very good points, Jack. So let's move on to another abstract, which is the LBA9000. This is the KEYNOTE-789 trial. In my opinion, this is the most important negative phase 3 trial in lung cancer in a while. This is a trial looking at pemetrexed platinum with or without pembrolizumab in patients who have EGFR mutation-positive metastatic non-small cell lung cancer. So, what are your key takeaways, Jack?  Dr. Jack West: Well, I would say essentially we've been waiting to figure out what is the best treatment approach for patients with acquired resistance after osimertinib. And most of the patients had received osimertinib for their EGFR mutation-positive non-small cell. This is essentially KEYNOTE-189 being run in the EGFR mutation-positive patients after they've exhausted at least the major benefit of EGFR TKI therapy.   What we saw was a hazard ratio for progression-free survival of 0.8. It didn't quite make it across the threshold for efficacy, a significant difference. And so it missed that efficacy boundary. And overall survival, the hazard ratio is 0.84, also missing the efficacy boundary. When you look at the actual curves, they show modest separation, nothing eye-popping, certainly compared to some of the other trials we're talking about. But I wouldn't say they show no benefit. And I think that's, to me, why there's really still a role for a nuanced thought process and maybe some discussion about how negative this is. This is not, in my mind, stone-cold negative with no patients benefiting from immunotherapy. This is a trial that really suggests that there's a subset of patients who are benefiting from immunotherapy.   And we've also seen going back to subset analysis of the IMpower150 trial and also the ORIENT-31 trial with sintilimab and a bevacizumab biosimilar, another anti-VEGF inhibitor. These trials both really indicated a benefit in this population after EGFR TKI therapy of immunotherapy combined with VEGF. I think there could still be a value in there. I don't want to be a Pollyanna or too open-minded, but I think that there was at least a suggestion that this could still be a fruitful avenue. I think that this is still something we should do additional studies on that could bear fruit. I wouldn't close the door and categorically say this is just never going to translate to any benefit for any of these patients.   Dr. Vamsi Velcheti: The key thing, though, is, like in EGFR mutant patients I think in the previous studies as well, the response rates with single-agent PD-1 have been very minimal. And I think one of the things that's actually very important to highlight is in the operative setting, the early-stage setting, unfortunately, some of the trials with immunotherapy have included patients with an EGFR mutation. And now we have a treatment option for those patients within the adjuvant setting, especially osimertinib. We just heard from the ADAURA trial, which has a clear significant overall survival benefit. So I think it's really important to test for EGFR mutation in all stages. And if somebody with the early stage has an EGFR mutation, adjuvant immunotherapy, or perioperative immunotherapy may not be the best option for those patients.  Dr. Jack West: Right. I agree with that, although it is interesting that the KEYNOTE-671 trial did have some small population of patients with an EGFR mutation, and in that subset analysis, they seem to benefit from the pembrolizumab. I would not say that we should divert from ADAURA, but I'm just not as sure that our previous statement and mindset that immunotherapy just categorically doesn't work for patients with driver mutations is that simple.   First of all, there is some heterogeneity about which driver mutation, and the ALK-positive patients seem to really get no benefit. But I think there's still some questions about immunotherapy for EGFR. Certainly, patients with KRAS or BRAF V600E seem to benefit like the broader range of patients. And I would also say maybe it's different whether you're giving immunotherapy combined with chemotherapy versus as monotherapy. So that's why I'm just not that sure we really can characterize this that well yet.   The one additional point I would make about KEYNOTE-789 and the potential role of immunotherapy is that some experts in thoracic oncology and general oncologists alike may prefer to introduce chemotherapy at a time of progression, but keep the osimertinib going, maybe particularly for patients with brain metastases, whether current or a history of them, where we really feel that the osimertinib adds a critical component to CNS control. We don't want to ever give osimertinib or probably other EGFR TKIs concurrently with immunotherapy. So that's just a factor that we'd really want to consider when we're prioritizing where to fit in immunotherapy, if at all.  Dr. Vamsi Velcheti: Thank you, Jack. And let's move on to the next abstract, Abstract 9002. This is a pivotal study of results from the sunvozertinib, which is an EGFR exon 20 insertion site mutation drug. There's some very promising data. Jack, how do you feel this study is going to influence practice?  Dr. Jack West: Well, this is not an agent we have access to broadly yet, but I was quite impressed by it overall. I didn't mention it. We talked about it in the pre-ASCO discussion, and it was really one that I would mark as potentially practice-changing when we can get it. DZD 9008 or sunvozertinib is a potent inhibitor of exon 20 insertion mutations, and this was 97 patients, and the majority had had a couple of lines of prior therapy. They had to have gotten chemo, and the response rate was 60%, and it was really comparable efficacy with the different mutation subtypes.   I think that the main thing that I would want to clarify a little better in my own patient population is how well the drug is really tolerated. We talked about that there was not really much grade 3 toxicity and that's true, but diarrhea rates were 67%, even though it was grade 3 and just about 8%. But grade 2 diarrhea or grade 2 rash in patients who are on this therapy, we hope for a long time, I think is something we shouldn't minimize. And I think that particularly our mindset about toxicity needs to be different when we're talking about giving a treatment for 2 or 4 cycles and then being done with it versus something we hope we're going to be giving longitudinally. And we really don't want to minimize the potential impact on the quality of life of patients who are experiencing grade 2 rash, diarrhea, or paronychia for months and months, maybe more than a year at a time.   But that said, this is twice the response rate if not more than that of what we have already had for patients with this molecular aberration with an exon 20 insertion. So I think it's compelling and I think that it's going to be really valuable to offer to our patients. I just would like to clarify better how well patients who are actually on it are feeling when you incorporate the potentially chronic toxicity issues.  Dr. Vamsi Velcheti: Thank you, Jack. And let's move on to the last abstract. This the LUNAR study, LBA9005. This is a positive phase 3 study that looked at tumor-treating fields or TTF therapy with standard of care treatments in metastatic non-small-cell lung cancer following platinum failure. This has been talked about a lot at ASCO, and Jack I'm eager to hear your key takeaways about this study.  Dr. Jack West: Well, we knew from a press release several months ago, I think back in February, that there was a significant improvement in overall survival with the addition of tumor-treated fields. Again, this concept that electric fields can lead to antimitotic effect and potentially downstream induction of immunogenic cell death and enhanced immune response, that's at least the concept. And it's of course established, has utility in patients with glioblastoma, although kind of, I would say underutilized because it can be cumbersome. And I think that's one of the things we need to factor in is that this is not the easiest approach to pursue.   But we don't have that many therapies that improve overall survival significantly in previously treated patients with non-small cell lung cancer. So, I think there's good reason to focus on this and ask how beneficial it is. It was notable, it was pretty much an even split of patients enrolled on the trial, 276 patients total, but about half had gotten chemo but not gotten immunotherapy before. And then the other half, I would say the clear majority, had gotten immunotherapy as well as chemo and got docetaxel-based treatment.     And the overall survival benefit was significant for the intent to treat total population with a hazard ratio of 0.74 and a difference in 3-year survival of 18% favoring the addition of tumor-treating fields on the chest versus 7% in the patients who didn't. It really seemed to separate between the patients who had not had an immune checkpoint inhibitor and got tumor-treating fields with the checkpoint inhibitor where the hazard ratio is 0.63 and those who got tumor-treating fields with docetaxel where the hazard ratio was 0.81. So it really wasn't significant in this population.  Toxicity, no real surprises compared to what we already knew about tumor-treating fields. Mostly dermatitis, but I would say that one of the kind of unmeasured issues is that this is a device that people have to wear on their chest carrying a battery pack with them all day long. It's essentially all the waking day, and so I think that's at least cumbersome. I wouldn't call it prohibitive, but it's a challenge. And I think we need to really ask whether the juice is worth the squeeze, whether the benefit is that compelling. And I question that when we're talking about an agent that doesn't significantly move the needle against docetaxel alone.   Again, this is a population where in the U.S. we have ramucirumab to add to docetaxel. Not everyone does that. It's not uniform, but that has a statistically significant, though modest survival benefit associated with that. We don't do better than that with tumor treating fields. And so, I think that this is an option that merits discussion and some patients may opt for it, but I suspect that most of my patients would not find the absolute difference to be that compelling for the challenges it incurs. I don't know what your perspective is here.  Dr. Vamsi Velcheti: I completely agree, Jack. And I think the study design and just the fact that the standard of care has changed over the last 5, actually 6 years since the study has been open. And I'm not really so sure I could really make much sense of the data in terms of the standard of care combination with TTF providing more benefit. And I think there are more questions than answers here and I'm not so sure which populations would benefit the most. And I think, I hate to say this, but this is a nice proof of concept. I hate to say this because it's a phase 3 study and it's a positive phase 3 study, but it's clinical relevance with the current standard of care, I think, I'm not really sure how much of an impact this would really have.    Well, Jack, I've really enjoyed speaking with you about these key advances in lung cancer that were featured at the 2023 ASCO Annual Meeting. Our listeners will find links to all the studies discussed today in the transcript of this episode. Thank you so much, Jack, for joining us today.  Dr. Jack West: Always a pleasure. Thanks so much.  Dr. Vamsi Velcheti: And just like that, we've reached the end of another enriching episode. But remember, like all good things, this too must come to an end, but only until we meet again. We really would like your feedback on the podcast. If you enjoyed the podcast, please 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:   Dr. Vamsidhar Velcheti   @VamsiVelcheti   Dr. H. Jack West   @JackWestMD   Follow ASCO on social media:    @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn      Disclosures:    Dr. Vamsidhar Velcheti:   Honoraria: ITeos Therapeutics   Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus   Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline     Dr. Jack West:   Honoraria: AstraZeneca, Genentech/Roche, Merck, Takeda, Mirati, Regneron, Amgen, Abbvie   Consulting or Advisory Role: AstraZeneca, Genentech/Roche, Merck, Takeda, Mirati Therapeutics, Regneron, Amgen, Abbvie, Summit Therapeutics   Speakers' Bureau: Takeda, Merck, AstraZeneca        

Drs. Vamsi Velcheti and Jack West discuss key abstracts in advanced SCLC and NSCLC, along with highlighting the largest known data set correlating ctDNA levels and efficacy outcomes in the EMPOWER-Lung 1 trial, in advance of the 2023 ASCO Annual Meeting. TRANSCRIPT Dr. Vamsidhar Velcheti: Hello, I am Dr. Vamsidhar Velcheti, your guest host of the ASCO Daily News Podcast today. I am a professor of medicine at NYU Grossman School of Medicine and the director of thoracic oncology at Perlmutter Cancer Center at NYU Langone Health. I am delighted to welcome Dr. Jack West, a thoracic oncologist and associate professor in medicine at the City of Hope Comprehensive Cancer Center.                                  Today, we'll be discussing key posters and oral abstracts in lung cancer that will be featured at the 2023 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode and disclosures relating to all episodes of the podcast are available on our transcripts at asco.org/DNpod.  Jack, it's great to have you on the podcast today. Dr. Jack West: Well, thank you so much, it's my pleasure to be here.  Dr. Vamsidhar Velcheti: Let's begin with Abstract 8512. This is the follow-up of the Gronberg trial, the Danish trial of BID thoracic radiation for limited-stage small cell lung cancer. What are your key takeaways from this trial? Dr. Jack West: Well, as you noted, this has been presented before a few years ago. It's a trial for limited-stage small cell lung cancer and it directly compared chemotherapy with either 45 Gray or 60 Gray of chest radiation delivered twice daily. It's not an enormous study, it's 170 eligible patients. And years ago, we saw that the efficacy endpoints looked very promising for the patients who received a higher dose of 60 Gray on a BID schedule, which is above our standard. We generally either give 45 Gray BID or probably more commonly in the US and I think globally give maybe 60 Gray on a once-a-day schedule. But the efficacy looked quite promising and without any clear increase in the toxicity of it. And really, despite the impressive results, this hasn't changed practice. It is not a large study and I think that I would say that most of the radiation oncology world has been reserving judgment until potentially seeing a larger study.  But what's being presented at ASCO are the longer-term results that continue to look excellent. You have a progression-free survival median of 18.6 months versus 10.9 months. That's not statistically significant but has a hazard ratio of 0.76 associated with it. And the median overall survival is even more pronounced of 43.5 months favoring the 60 Gray arm compared to 22.6 months in 45 Gray on a BID schedule that has a hazard ratio of 0.69. And this is statistically significant. The authors note that they will be presenting five-year overall survival as well. And there's also just passing mention that, as was seen previously, there was no increase in toxicity, no prohibitive toxicity. So I don't think it's necessarily going to change practice because the numbers of patients, which I think are really the leading concern, hasn't changed. But these very promising results still hold up over time and I think should compel us to carefully assess this as an option to potentially increase outcomes for this challenging setting where progress is slow to come. Dr. Vamsidhar Velcheti: Yeah, I completely agree, Jack. And I think one of the things that we have seen, at least in the non-small cell setting, like the higher dose of conventional radiation is not superior to the 45 Gray, BID dosing. I think there were some studies with CALGB and the Gronberg trial, but I think at the end of the day, it comes down to patient conveniencer. It's not often feasible for patients to come in twice a day for radiation. That might be something that might limit utilization here.  Dr. Jack West: I think that's a very good point. It's just difficult when you have the potential for higher cure rates, but it is at least challenging, if not completely infeasible. But I really agree with you that that's a big part of why it's underutilized relative to the strength of the data for BID. But we have to be able to actually administer these. Dr. Vamsidhar Velcheti: So let's move on to another trial. And again, we've seen the data before. This is Abstract 8521, the CheckMate-816 trial. They reported the three-year results of the neoadjuvant nivolumab chemotherapy versus chemotherapy by definitive surgery in patients with resected non-smoker lung cancer. What is the data that's being presented at ASCO this year? Dr. Jack West: So yes, as you mentioned, we've seen data on CheckMate-816 for a few years now. It's been published in the New England Journal of Medicine and it's FDA-approved and has become a standard of care, if not the standard of care, but there are many dimensions to this. And one of the questions has been what happens to the patients who did not undergo surgery, which was about 17% of patients on the chemoimmunotherapy arm, a full quarter of patients on the chemo arm. What happened to these folks? And that's what is being presented by Dr. Jonathan Spicer, a thoracic surgeon in Montreal who's been heavily involved with this trial. And I think that's going to be the overwhelming focus of this.  And what is reported in the abstract, and I'm sure we'll see more interesting results, is that the outcomes are superior in the patients who received chemoimmunotherapy with nivolumab, in the patients who did not undergo surgery as well as those who did. Specifically, they report on the median time before death or distant metastases, and that was 24.8 months as a median for the chemoimmunotherapy arm versus 15.6 months for the patients who receive neoadjuvant chemo alone. The hazard ratio for that's 0.63. There was also a striking difference in the three-year survival rates, 36% versus 13% also favoring chemo and nivolumab.  They also talked about the actual treatments that patients received when they didn't have surgery, and about 60% in both of those arms received radiation instead of surgery, and about half the patients also received additional systemic therapy. So we will see more. But I think it helps to address one lingering question of what happens to the patients who did not end up pursuing surgery and showing that the results were more favorable for the recipients of chemo nivolumab, even in that subset. Dr. Vamsidhar Velcheti: It's simply fascinating how the field is evolving in the perioperative space, Jack. And there are more unanswered questions here and up for debate for years with the recent agent trials we had seen at AACR. We've seen the same kind of trend even with the agent, I think it was 20%, who did not make it to surgery. A lot of them are like stage 3 patients. So it begs the question, are we kind of just being more aggressive with induction therapy? Maybe some of these patients are biologically or anatomically not bound to have surgery. I mean, it's hard to really tell. Dr. Jack West: It really is important for us to still select appropriate patients for this, rather than become overly ambitious and try to shoehorn patients who are really not ideal or appropriate candidates for surgery and anticipate or have kind of aspirational resectability if they aren't de novo great candidates for surgery. We, of course, need to remember that chemoradiation followed by consolidation durvalumab on the PACIFIC trial is not some terrible consolation prize. We've done remarkably better with this over the years, and it's a very strong option.  Dr. Vamsidhar Velcheti: Exactly. The other open question, but of course this abstract doesn't really address is, what do you do with all the patients who perhaps have major pathologic responses and what do you do after surgery? That's kind of an open question, and we probably need a better way to determine who might need adjuvant therapy or surgery. I don't know if you have any thoughts on that.  Dr. Jack West: As you say, I think that's a big question, a gaping hole in our knowledge base, but it's not addressed here. I think we are going to be struggling with that in the coming years.   Dr. Vamsidhar Velcheti: Right. So let's move on to Abstract 9002. This is a report of the first pivotal study results of DZD9008 sunvozertinib in patients with exon 20 EGFR mutation. What are your key takeaways from the study? Dr. Jack West: So I would say obviously we have a couple of agents that target EGFR exon 20 mutations, but unfortunately, neither of the agents that are commercially available is especially active. And they certainly have toxicity challenges, whether it's amivantinab or mobocertinib,  they both share some challenges and they're not as efficacious as some of the other targeted therapies we use in different molecular settings. So I would say there's still some unmet need here. And these results with sunvozertinib DZD9008 selective irreversible EGFRexon20 insertion inhibitor really got my attention as very impressive. These are patients who were heavily pretreated. The median was two prior lines of therapy. This is not de novo first line, and that's a setting where it's pretty hard to see response rates that are over 30 or 40%, but what they actually report is about 60.8% response rate and nearly 100 patients assessed. They also looked at patients who had brain metastases and 31 patients in their sample had de novo metastases and the intracranial response rate was 48.5%, so nearly half.  This is, of course, something that we hope to see as a pattern when we have a targeted therapy that's very effective for the right target, not just overall extracranial, but intracranial efficacy. And we're going to need to see the details on the tolerability because, as I mentioned, the available agents now have the dual challenge of just modest efficacy and really quite challenging, particularly GI toxicities and amivantamab has issues also with infusion reactions. So some work there and I think there's room to improve on that. This looks to me very promising and I would welcome having the opportunity to use it in my patients who have an exon20 mutation.  Dr. Vamsidhar Velcheti: Yeah, I think certainly the brain intracranial activity is perhaps going to be the differentiator here. Given that mobocertinib has limited intracranial activity, I think that's very encouraging to see. So let's move on to the next abstract, the SCARLET trial, Abstract 9006. So this is a clinical trial of sotorasib plus chemotherapy in KRAS G12C-positive patients. Can you tell us a little bit more about this study, Dr. West? Dr. Jack West: Sure. So this was a single-arm phase II trial. It's not large, it's 30 patients, but we really have yet to see results that would compel me to move sotorasib into the first-line setting. I was a little underwhelmed with the CodeBreaK 200 results that didn't beat docetaxel for survival in the second-line setting. But here it's a combination of carboplatin pemetrexed with sodorasib in the first-line setting in patients, of course, with a KRAS G12C mutation and nonsquamous histology. And the reported response rate by independent review is 88.9%, which is quite impressive. The median PFS is not reached yet. The PFS at six months is 61.2%. So I think we'll need to see the full data set, but that really impresses me as a very relevant finding. So I would love to learn more about this. And I think that if it is anything close to holding up with these response rates, close to 90%, I mean, even if it's 70 or 80%, I think that is compelling enough to really want to study this further in the first line setting and maybe a path to getting KRAS inhibitors used in the front line. Dr. Vamsidhar Velcheti: Yeah, I completely agree. And I think with all the issues around the combination with checkpoint inhibitors, especially with sotorasib high liver toxicity, so I think the only way this could move into the frontline is with combination with chemotherapy, especially in certain subsets like KEAP1 CUL drug patients, STK11/KEAP1 patients where immunotherapy historically underperforms. So it'll be interesting to see how this can evolve.  So, moving on to Abstract 9012, this is a clinical trial evaluating a often very neglected patient population. This is a retrospective study of chemo without immunotherapy in the elderly population of patients with PD-L1-positive tumors. So what is your takeaway from this study? Dr. Jack West: I would say that it really complements in my mind the presentation by Dr. Akinboro and colleagues from the FDA last year at ASCO, which was looking at the data for the trials of immunotherapy or chemoimmunotherapy in patients with high PD-L1 50% or higher. And what they found was that there was an improvement in response rate and progression-free survival and a trend, but not a significant difference in overall survival favoring chemoimmunotherapy in those patients. But they also noted that patients who were 75 or older did not seem to benefit from chemoimmunotherapy relative to immunotherapy alone. Now, that is in patients with high tumor PD-L1. This is looking specifically at patients who are 75 and older in Japan, 58 centers, and we're talking about over 1,200 patients, 1,245. And they looked at patients with any PD-L1. So the full spectrum, about 22% had PD-L1 less than 1%,31%, one to 49%, and just over a third, 34% with PD-L1 over 50%. I would presume the balance, that missing 13%, was not tested. But these are real-world data and they have strengths and limitations relative to controlled clinical trials.  But I think that there is some power in numbers and real-world data. And what they saw was that the patients who received chemoimmunotherapy had a median overall survival of 20 months. It was 19.8 months with a checkpoint inhibitor alone. And those data for both of those conditions are far better than a platinum doublet alone with a median overall survival of 12.8 months. Single-agent chemo just median overall survival of 9.5 months. And then when they looked at toxicities, saw that the grade three or higher immune-related adverse events was clearly higher in the patients who had chemoimmunotherapy, they had a greater need for steroids and a greater probability of pneumonitis than the patients over 75 who received a checkpoint inhibitor alone.  And so I would say it's not randomized data. You can only take this so far, but the fact is that it, I think, complements what we saw from the FDA. And that would help me in a situation where we need to make a nuanced decision, there's competing potential standards of care. I think this is informative along with the IPSOS trial that has been presented in some other settings and shows a benefit for in that setting was atezolizumab, I believe, first as the immunotherapy for older patients and PS2. So I think that we're seeing converging evidence to support this concept. Dr. Vamsidhar Velcheti: Yeah, and I completely agree. And I think sometimes the clinical nuances at the individual patient level, I think there are so many other factors that we can actually look at the real-world data, like, for example, tumor burden and medical tomographies. There's so many things that we need to factor into while making those decisions.  Let's move on to the next abstract. This is Abstract 9022. This is an abstract looking at correlations of ctDNA levels and efficacy outcomes in the EMPOWER-Lung 1 trial. What are your key takeaways from this study? Dr. Jack West: I would love to use ctDNA for clinical decision-making in a few years. I think it could be as pivotal as PET scans, but we don't have the data yet to show that you can use the results to improve outcomes. But this is looking at ctDNA in a different setting, as you mentioned, it's looking at the EMPOWER-Lung 1 trial, which was cemiplimab versus chemotherapy in patients with PD-L1 over 50% and did not have a driver mutation. They had ctDNA samples available from 175 patients who were pretty evenly split between chemo and checkpoint inhibitor cemiplimab. What they found was that molecular response, or particularly complete molecular response, if it was seen as in complete eradication of ctDNA at week nine, so after three cycles, was highly correlated with imaging-based response for patients who got cemiplimab. It was not correlated for the patients who got chemotherapy and, perhaps not surprisingly, the patients who had a complete molecular response that was associated with the best overall survival, an immediate overall survival of 29 months compared to the rather dismal results for patients who had no drop in their ctDNA, where the median overall survival was just eight months.  So, I think that it would be wonderful to be able to use this as a help. We know that sometimes patients have ambiguous imaging. There is the possibility of pseudoprogression and just potentially pneumonitis, making it difficult to interpret. I think that ctDNA could be helpful in that situation, but also for early feedback on who might benefit from intensification and adding chemotherapy, who we should cut our losses and switch to something else other than cemiplimab. And in the best-case scenarios, we do have a subset of patients who are doing extraordinarily well, potentially one or a couple of years later, and we just don't know if or whether to stop it and whether patients can do just as well after stopping after a prolonged period on treatment compared to staying on it. And we don't want to give this for years longer at the expense of cumulative toxicities and requiring a patient to come in for ongoing treatments month after month, year after year, for any longer than they would need.  I think that there's great potential utility for this as a concept. But again, at some point, what we'll really need is not to just apply this retrospectively, but prospectively to guide therapeutic decisions, to see if we can have patients do better by intensifying for those patients who need it or de-intensifying for patients who don't. Dr. Vamsidhar Velcheti: It's great, Jack. And I completely agree. I think those kinds of de-escalation trials are very much needed. I'm hoping that we'll get there very soon.   Thank you so much, Dr. West, for sharing your valuable insights with us today on the ASCO Daily News Podcast. We really appreciate your time. Thank you so much. Look forward to seeing you in Chicago. Dr. Jack West: Awesome. Great.  Dr. Vamsidhar Velcheti: And I'd like to thank all the listeners for joining us 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 so much.  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, experiences, 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. Vamsidhar Velcheti @VamsiVelcheti Dr. H. Jack West @JackWestMD  Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn   Disclosures:  Dr. Vamsidhar Velcheti: Honoraria: ITeos Therapeutics Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline  Dr. Jack West: Honoraria: AstraZeneca, Genentech/Roche, Merck, Takeda, Mirati, Regneron, Amgen, Abbvie Consulting or Advisory Role: AstraZeneca, Genentech/Roche, Merck, Takeda, Mirati Therapeutics, Regneron, Amgen, Abbvie, Summit Therapeutics Speakers' Bureau: Takeda, Merck, AstraZeneca

Host Dr. John Sweetenham and guests Dr. Karen Reckamp and Dr. Harpreet Singh discuss the S2302 Pragmatica-Lung trial, a streamlined, real-world clinical trial that is poised to simplify and transform the entire clinical trials model as we know it. TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the associate director for cancer network clinical affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and host of the ASCO Daily News Podcast.  Today, we are going to be discussing a streamlined, real-world clinical trial from the Southwest Oncology Group (SWOG), which is S2302, also known as the Pragmatica-Lung trial. This study is poised to simplify and transform the entire clinical trials model as we know it. Joining me for this discussion is the trial's lead investigator, Dr. Karen Reckamp. Dr. Reckamp is a clinical professor, director of the Division of Medical Oncology, and associate director for clinical research at Cedars-Sinai Samuel Oschin Cancer Center. I'm also delighted to welcome Dr. Harpreet Singh, the director of 1 of 3 divisions of oncology at the U.S. Food and Drug Administration. She will discuss the FDA's views on streamlining clinical trials to reach more representative groups of patients and will also more broadly address some of the key questions that regulators consider when deciding on whether real-world data can substitute for randomized controlled trials. Our full disclosures are available in the transcript of this episode, and disclosures relating to all episodes of the podcast are available on our transcripts at asco.org/DNpod. Dr. Reckamp and Dr. Singh, it's a great pleasure to have you on the podcast today. Dr. Karen Reckamp: Thank you for having us. Dr. John Sweetenham: Dr. Reckamp, I'm going to start with you if I may and ask if you could give us some background on S2302, the Pragmatica-Lung trial for non-small cell lung cancer. Dr. Karen Reckamp: Sure. The Pragmatica-Lung trial really started with the sub-study from Lung-MAP, which was called S1800A, and it was a randomized phase 2 trial that evaluated pembrolizumab and ramucirumab versus standard of care for patients who had previously received chemotherapy and immunotherapy with advanced non-small cell lung cancer and had had disease progression. And in this phase 2 trial, we found that there was an improvement in overall survival with a hazard ratio of 0.69% and survival of 14.5 months for pembrolizumab and ramucirumab, and 11.6 months for standard of care. And with that, we had again a randomized phase 2 trial, but the study was small. And so, trying to think about how to move this to the next level to get phase 3 data, we started thinking about how to do this in a way that would reduce the timelines and potentially move this treatment to patients more quickly than standard registrational, randomized phase 3 trials. And that's kind of where S2302 and Pragmatica-Lung started. Dr. John Sweetenham: So, can you tell us in a little more detail how the dramatically streamlined pragmatic design of this trial is going to hopefully simplify trial design and trial conduct in the future beyond non-small cell lung cancer?  Dr. Karen Reckamp: I think the important piece of this—and we have Dr. Singh here to speak to the FDA part—but this has been a partnership with the FDA and CTEP [NCI's Cancer Therapy Evaluation Program]. Really, our goal was to try and find a way to run trials in a more streamlined way. One of our colleagues at CTEP during this process said, “If this is not making you uncomfortable, then you're not doing it right.” So, the first thing we did was kind of lean into the discomfort because for those of us who have been writing trials and putting trials together for the last 20-plus years, this is dramatically different. And we're really looking at one question, and that is overall survival. We're trying to validate the overall survival we saw in S1800A. And with that, we stripped away all the unnecessary data collection that comes along with other types of registrational issues that come with randomized phase 3 trials. And then, we also looked at patient burden and really opened it up. So, again, pragmatically, making this practical, allowing investigators to be empowered to treat patients how they normally would in their own practice. And so, moving forward, again, for types of trials where we have drugs whose toxicity profiles are well known, they're used in practice but using novel combinations for a subset of patients who have limited treatment options available, this could really change the paradigm moving forward for these types of trials in multiple diseases. Dr. John Sweetenham: Yeah, thanks. And in addition to simplifying the trial design, obviously, one of the goals here is to have a study population which is more representative of the patients who are seen typically in community practice. Hopefully, we'll overcome some of the known disparities that we see in clinical trial accrual. Could you speak just a little bit to how the study design and the organization of the study helps to achieve that? Dr. Karen Reckamp: So, I think it's on several levels, but we are looking to allow this to be more generalizable and allow a more diverse population into this study. First, by again stripping down the eligibility criteria to only the absolute essential criteria for understanding our scientific question. And so, we don't require imaging studies to be uploaded or presented. If the patient has progression, it's based on the investigator's opinion. And so, we don't need to be searching for outside scans or things like that. We don't have tissue requirements, and we don't even actually have lab requirements. If this is a patient, you would treat your standard of care practice with the standard of care regimens; those are the labs that you do. So, it's all based on standard of care. So, by doing this based on standard of care, it really allows almost any patient to enroll. And then we have outreach. We have our DEI group and our community practices very well engaged to make sure that we have broad reach. Having this open through NCTN [NCI's National Clinical Trials Network] will make sure that we get this to multiple practices in far-reaching parts across the United States. Dr. John Sweetenham: Yeah, I think that's excellent. And you've already alluded to the fact that the data collection requirements for the study are going to be kind of pared down to the absolute minimum and that's going to include, I believe, toxicity reporting as well. So, can you comment a little bit on that and, specifically, what your plans are for reporting toxicity in this trial? Dr. Karen Reckamp: Yes, you're correct. This is significantly pared down from what we're used to doing. And so, most clinical trial offices are struggling with staffing and making sure that their patients have enough staff and that they have enough staff to get patients onto trials efficiently, and then getting the data in is always a challenge for sites. So, we have really, again, working with our partners, working with the FDA, and with CTEP, we have minimized what we are going to collect on patients. So, we're collecting survival and vital status on patients. We are collecting the background standard information that we collect on kind of prior therapies, and we are collecting only unexpected grade 3 and higher adverse events. And so, thinking about these drugs—ramucirumab and pembrolizumab—we know how these drugs work, we know the toxicity profile, we're using them in combinations and single agents in multiple tumor types. And so, thinking about most of the immune-related adverse events wouldn't even be reportable because they're expected. And so, a large number of data that is normally collected would not be collected here. And, as noted, we don't collect scans, we don't collect labs, we're not collecting con-meds, start and stop dates. A lot of that burden of data collection, but also data auditing and queries, goes away. It should be a significantly easier trial to perform by sites.  Dr. John Sweetenham: And can you just update us on the status of the trial right now? Dr. Karen Reckamp: We're in the process of pre-activation, and so, if you're an NCTN site, you can actually go in and do some pre-training and take a look at the draft protocol. And we are anticipating approval sometime in early March. Dr. John Sweetenham: Great. Congratulations on getting this trial launched and underway because I know that the word “groundbreaking” is used a lot, but I think that, obviously, if this trial proves to be the success that it looks like it will be, then it's going to have, I think, major implications for study design in the future. And that's going to lead me to ask a couple of questions to Dr. Singh. And the first one of those is the FDA's decision to consider data from a simplified pragmatic trial design like this, which uses more limited clinical information, is really kind of almost revolutionary. And could you comment a little on this from the FDA perspective and how you think it's going to influence the future of clinical trials and the future of cross-trials? Dr. Harpreet Singh: Well, thanks so much for the question, and thanks for having me. I want to push back on that just a little bit because I think, for what it's worth, the FDA has been advocating for trial efficiencies in oncology for many years. And, of course, as you know, our current commissioner, Dr. Robert Califf, is very vested in this concept. And certainly, the idea of pragmatic trial has been there in the field of cardiology for some time.  In terms of this trial, in particular, in coming to oncology, I do think actually putting pen to paper and drafting the protocol, which we did really in cohesion with SWOG and many calls with Karen and others who were a part of this, that collaborative piece, I think, is groundbreaking because what we saw here was a great deal of discomfort, actually around everything that we were stripping down. We sensed a lot of discomfort in terms of including various, like you mentioned, safety issues, safety reporting not being perhaps as rigorous as we're accustomed to seeing at the FDA. And certainly, investigators are accustomed to collecting other endpoints besides overall survival, like time to progression, but the real-world version of that, or time to next therapy. And so, one very difficult lesson that I've had to learn, and we've had to learn, is that you have to really learn to say no to some very interesting trial design elements that are not essential to the big question here, which is, does this combination regimen offer an improvement in survival over the control? So, while I do think the actual organizational and structural piece of this, now that it's actually stood up, is groundbreaking, I think that the idea of pragmatic trials and incorporating clinical care into the idea of answering a clinical question as opposed to the traditional randomized clinical trial is a concept that's been around. I'm just thrilled to see it actually occur in this very, I think, ideal setting for patients with lung cancer. Dr. John Sweetenham: Yeah, absolutely. I want to broaden the scope of what we're discussing here just a little bit, perhaps to talk a little more about the “real world” and “real-world data.” More real-world data is being considered in regulatory decision-making. And one of the questions I have, again, from an FDA perspective, is that everyone still, I think, regards randomized controlled trials as the gold standard for evaluating efficacy if not effectiveness, of various interventions. What are the key questions that you consider when deciding whether any kind of real-world data analysis is a good substitute for a randomized controlled trial?  Dr. Harpreet Singh: Well, thank you for the question about how FDA considers real-world data when we consider this to be appropriate. There are many nuances to this. So, first of all, what is real-world data? And there's actually a distinction between real-world data, which is just simply a source used in observational studies traditionally. But real-world data is not specifically a trial design; it's just data. Whereas real-world evidence, which is evaluating the benefits and risks which are derived from real-world data, may come from things like electronic health records. It's not either-or. So, for example, in a pragmatic trial, you could use a blended approach where you have some components of real-world data or real-world practice, which we may consider kind of part of real-world data, but while retaining some elements of randomized control trials. So, I think when FDA considers real-world evidence, so I'll say that instead of data, it usually would be a source like a very high-quality registry or data obtained through a very well-designed observational study. And this would be in settings of perhaps super rare diseases in which randomization is either not feasible or, in some cases, where you may have preliminary data which suggests that randomization is not ethical. But we agree with the general idea that the gold standard is randomization.  And that's what I love about this pragmatic trial, is that you are retaining the benefit of randomization while bringing pragmatic elements in, bringing the trial to patients and really incorporating clinical practice into the trial, as opposed to the reverse, where you're having patients enrolled on a traditional trial where the visits are outside of routine. Dr. John Sweetenham: Thanks for drawing that distinction between real-world evidence and real-world data because I think the two expressions are sometimes used a little carelessly, as maybe I just did. But certainly, one of the things that I've observed over the last several years since we started to incorporate real-world data or real-world evidence into our kind of oncology lexicon is that real-world data has been used in a fairly relaxed, let's say, way and certainly any relatively small series which has been registry based or retrospective, there's been a tendency to use this term called real-world data, which personally, I've certainly seen applied to patients who are undergoing very intensive therapies such as CAR T. And certainly, when I look at the patient characteristics in those elements of so-called real-world data, it's a long way from the real world that I'm familiar with in my own practice. And so, I do think that the term has been used very loosely. And your point about real-world evidence is an important one, I think. People are still questioning whether real-world evidence in oncology is truly valid. And I think to some extent, you've already answered that question.  Do you think that there are mistakes and pitfalls that investigators can avoid when they're looking at real-world evidence? Dr. Karen Reckamp: Sure. I mean, I think the first point of clarification is, are we looking at this evidence to support use of an oncology drug in clinical practice, or are you an investigator working to bring real-world evidence to the FDA for drug approval? But either way, no matter what scenario you're in, I think the first question you must ask yourself is, is this data fit for purpose? And what does that actually mean, ‘fit for purpose'? And I think it goes to things like, are the patients well-matched? So, there's this very complex process, but the concept is not complex of propensity score matching, which our statisticians do for us beautifully. But this idea of are the patients in this data set that you're looking at, this is just a collection of data, right? How relevant is it to the patient in front of you? Is there some sort of matching that's going on in terms of patient characteristic?  After that, you have to ask yourself about this kind of array of epidemiologic biases that are inherent in non-randomized comparisons. Like, is this contemporaneous data? So, if this data set came from a group of patients who started their therapy—this goes to the idea of the index date, okay, start of therapy—has the standard of care changed? Has supportive care become increasingly better? Obviously, the answer to that is yes. And so, if you have these contemporaneous mismatches, then can you actually really rely on this real-world data or evidence, either one, as you're applying it to your patient? So, I think if it's for regulatory purposes, certainly you could avoid many mistakes by coming to the FDA early and often, which we always recommend. And if it's you as a clinician, as a health care provider, looking at this collection of data, I think you do have to walk yourself through in a really basic kind of logical process of, “how well does this data apply to the scenario in which I want to use this therapy?” So, index date, selection, timing, patient characteristics, things like that. Dr. John Sweetenham: Yeah, great, thanks. And I'd like to maybe ask both of you for your comments on one final question, and this is circling back to the S2302 study. Intrinsic to the study design and the concept is that the population in this study will be truly representative of the “real world.” My two questions to both of you will be, first of all: What is the gold standard for representative? In other words, what does that really mean to have a representative population of patients with advanced non-small cell lung cancer? And secondly, do you have any safeguards in place in the course of the study designed to make sure that that study population doesn't get skewed in some way so that it becomes unrepresentative of the real world? So, Dr. Reckamp, maybe I can start with you and ask you for your comments about that. Dr. Karen Reckamp: Thank you. I think that's a very good question and something that we grappled with as we designed this study and really did keep coming back to that. So, I think when we talk about representation, most randomized trials don't have broad representation. They are very specific populations that we curate in order to take as much variability out of the trial as possible so that we can investigate just the experimental arm versus standard of care or whatever we're evaluating. And here, we've consciously made an effort to say we want to know how this works in a real practice and make this as generalizable as possible while still being safe. So, we have the premise of keeping patients safe as the number one goal of this trial. And then, we want to look at the survival data. So, we actually did lower the bar a bit and changed our hazard ratio. Our hazard ratio was 0.69% for the phase 2 trial. We loosened that a little bit for the phase 3 trial, knowing that the patients that are coming on to trial are not going to be perfect patients, and there may be a little more coming together of those curves. That being said, randomization is what is supposed to wash away all sins, which has been said many times as we put this trial together. And so, the randomization is really the goal, to utilize the randomization process in order to make sure that there is balance and that we are getting representation on both sides that will help us understand how the investigational arm is really doing in this population. It's not going to be perfect, and we are allowing for performance status 2 patients. But I think we all believe that this is really important because there's a large proportion of patients who have performance status 2 who never go on to trials, but in the real world, we treat them generally with the standard of care options that we use. So, I think this is really important for moving things forward, and will be groundbreaking in that way, too. Dr. John Sweetenham: Great, thank you. And Dr. Singh, just to add to that, will the FDA be looking at this from the perspective of making sure that the study population as a whole—accepting that randomization will hopefully cancel out some of the potential pitfalls there—but will the FDA be looking to make sure that the population as a whole is truly representative of what's out there in the real world?  Dr. Harpreet Singh: We always look at the population. We are always hopeful that, in general, the population is reflective of the disease for which—in this case, lung cancer. I think in this case, we were very hands-on with developing the protocol, and it is our hope and it's our expectation, and I think it very much will happen that you are going to see a very diverse and representative, more generalizable population here. I just want to add a piece to this because remember that traditional randomized clinical trials typically do have a more homogeneous patient population because a lot of this is designed around a de-risking strategy when you're bringing new drugs to market. One of the reasons we felt so comfortable stripping away, as Karen mentioned, no lab criteria. If the clinician says, “I think you're fit for this regimen, go ahead and enroll them.” We pushed for inclusion of PS 2 patients. We, the FDA, did. So, yes, we're going to be looking, but we do really hope that these really streamlined inclusion and exclusion criteria allow for that. And so there's other things too, like race, ethnicity, age. And so it starts with not excluding patients based on perhaps unfair or arbitrary cutoffs like labs. Not to say that performance status is arbitrary. But in this case, if the clinician deems you fit for this therapy, that is between the patient and the investigator and their judgment, which is really part of the element of real-world trials and this pragmatic element too.  I also wanted to add on this idea of diverse representation, we expect there to be a lot of extra, for lack of a better term, noise, in this trial, even though it's randomized. And so, part of the negotiation around designing this trial was the need for an increased sample size to try to account for some of what we expect to be perhaps unequal randomization, perhaps in terms of patient characteristics on either side, perhaps patients lost to follow-up, etc. And so, when we talk about pragmatic trials, one element is that you probably often may need an increased sample size to account for the increase in heterogeneity, not only in your patient population but perhaps in monitoring as well. Dr. John Sweetenham: Well, thank you both, Dr. Reckamp and Dr. Singh, for a great discussion today and for sharing your insights on these developing trends in clinical trial design. Dr. Reckamp and Dr. Singh, we'll be watching closely to see how the trial performs in the coming months and advances the concepts of pragmatic trial design that Dr. Singh mentioned earlier within the FDA. We obviously are very excited to see whether this change in trial conduct will enable you to meet new groups of patients and ultimately improve outcomes for them. So, thanks once again for being with us today. Dr. Harpreet Singh: Thanks so much. Dr. John Sweetenham: And thank you to our listeners for your time today. If you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. 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. John Sweetenham  Dr. Karen Reckamp  @ReckampK  Dr. Harpreet Singh  @harpreet_md Follow ASCO on social media:  @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn  Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness Dr. Karen Reckamp: Consulting/Advisory Role: Amgen, Takeda, AstraZeneca, Seattle Genetics, Genentech, Blueprint Medicines, Daiichi Sankyo/Lilly, EMD Serono, Janssen Oncology, Merck KGaA, GlaxoSmithKline, Mirati Therapeutics Research Funding (Institution): Genentech/Roche, Janssen Oncology, Calithera Biosciences, Elevation Oncology, Daiichi Sankyo/AstraZeneca, Blueprint Medicines Dr. Harpreet Singh: None Disclosed

We are kicking off the new year with a special podcast episode featuring Shawn Leland, CEO and Founder of Elevation Oncology! Shawn brings over a decade of experience in medical affairs and business development for the pharmaceutical and biotech industries, with a focus on building collaborations to realize the full potential of targeted and personalized therapeutics. His company, Elevation Oncology, is leading the way in novel cancer treatment, while always prioritizing the work/life balance and well-being of employees. Shawn stresses the importance of a flexible work environment that allows employees to be present in their careers and their homes. To perform at your best, he says, you need to have the time to sit back and refresh. Tune in now to learn about Shawn's journey and the exciting new developments happening at Elevation Oncology!

Welcome to "Dear Cancer," a takeover episode of Out of Patients with special guest hosts Dr. Mark Lewis, an oncologist from Intermountain Medical Center, and Stephanie Elsea, a volunteer patient advocate from The Lustgarten Foundation. Together with Matthew Zachary, Mark and Stephanie break down the latest cancer research medical jargon into human terms, especially with the help of another special guest, Matt's daughter, Hannah. With grace, humor, and passion, the three share personal stories that connect them deeply to this cause. They wish only to help patients strike that balancing act between hope and hope by banishing pessimism and embracing reality about their prognoses. Throughout the episode, the team covers everything from understanding different types of tumors, what biomarkers are (and their importance), and clinical trials can sound less, um.. "clinical." They also discuss the latest findings and some extremely positive results from the Crestone Research Study.See if biomarker testing is right for you, and sign up today at http://dearcancer.health/findout.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

In this episode, a part of our biomarker testing series, we are joined by Dr. Manish Patel, Director of Drug Development for Florida Cancer Specialists, to talk about biomarker testing in the community oncology setting - from the importance of emerging biomarkers to basket and umbrella trial designs.If you have any questions for today's guest or have a topic you would like to learn more about, email us at OnCallGPO@gmail.com.The content and information contained in this podcast is sponsored by Elevation Oncology. This podcast is for educational, and informational purposes only. This podcast does not constitute medical or other professional advice or services. No person should act or refrain from acting on the basis of content provided in any podcast or website without first seeking appropriate medical advice and counseling. The opinions expressed in this podcast are the opinions of the individual and may not reflect the opinions of IntrinsiQ or Elevation Oncology.

In this episode, a part of our biomarker testing series, we are joined by Dr. Manish Patel, Director of Drug Development for Florida Cancer Specialists, to talk about biomarker testing in the community oncology setting - from the advantages and disadvantages of liquid biopsies to the benefits of ordering test panels.If you have any questions for today's guest or have a topic you would like to learn more about, email us at OnCallGPO@gmail.com.The content and information contained in this podcast is sponsored by Elevation Oncology. This podcast is for educational, and informational purposes only. This podcast does not constitute medical or other professional advice or services. No person should act or refrain from acting on the basis of content provided in any podcast or website without first seeking appropriate medical advice and counseling. The opinions expressed in this podcast are the opinions of the individual and may not reflect the opinions of IntrinsiQ or Elevation Oncology.

In this episode of Occupation Station, 2008 ACPHS grad Shawn Leland talks about the personal, educational and professional ways he has been inspired to help people live longer, healthier lives. Some of that inspiration came to him through a clerkship rotation that didn't go as planned and instead landed him at Roswell Park Cancer Institute. While engaged in his studies, he was also seeing real health challenges in people he loved. He witnessed how important drug therapies were in helping them to live their best lives. After graduation, Leland says he experienced a big realization during a European Society of Medical Oncology conference and got an idea that led him to pull together the right researchers and financers to create a tumor agnostic drug development strategy. Even the name of Leland's company, Elevation Oncology, comes from a very inspired place. Leland has frequently been inspired along his career path; now he shares that inspiration with current and prospective ACPHS students. Learn more about your ad choices. Visit megaphone.fm/adchoices

In this episode of Occupation Station, 2008 ACPHS grad Shawn Leland talks about the personal, educational and professional ways he has been inspired to help people live longer, healthier lives. Some of that inspiration came to him through a clerkship rotation that didn't go as planned and instead landed him at Roswell Park Cancer Institute. While engaged in his studies, he was also seeing real health challenges in people he loved. He witnessed how important drug therapies were in helping them to live their best lives. After graduation, Leland says he experienced a big realization during a European Society of Medical Oncology conference and got an idea that led him to pull together the right researchers and financers to create a tumor agnostic drug development strategy. Even the name of Leland's company, Elevation Oncology, comes from a very inspired place. Leland has frequently been inspired along his career path; now he shares that inspiration with current and prospective ACPHS students. Learn more about your ad choices. Visit megaphone.fm/adchoices

In this episode, a part of our biomarker testing series, we are joined by Dr. Manish Patel, Director of Drug Development for Florida Cancer Specialists, to talk about the basics of biomarker testing – from identifying common testing approaches to comparing DNA and RNA sequencing. If you have any questions for today's guest or have a topic you would like to learn more about, email us at OnCallGPO@gmail.com. The content and information contained in this podcast is sponsored by Elevation Oncology. This podcast is for educational, and informational purposes only. This podcast does not constitute medical or other professional advice or services. No person should act or refrain from acting on the basis of content provided in any podcast or website without first seeking appropriate medical advice and counseling. The opinions expressed in this podcast are the opinions of the individual and may not reflect the opinions of IntrinsiQ or Elevation Oncology.

Shawn M. Leland is the Founder and Chief Executive Officer of Elevation Oncology overseeing all day-to-day operations. Shawn brings over a decade of experience in medical affairs and business development for the pharmaceutical/biotech industry, with a focus on building collaborations to realize the full potential of targeted and personalized therapeutics. Shawn has been involved in global transactions totaling more than $450 million in upfront payments and milestone payments at Eli Lilly, ARIAD Pharmaceuticals, Argos Therapeutics and Verastem Oncology. Shawn has also served as an expert strategic consultant for Catenion providing guidance on portfolio management for pharmaceutical/biotech companies. Shawn resides in Denver, Colorado and enjoys snowboarding, hiking and cycling.

Elevation Oncology is taking a new approach to leveraging the genome to guide development of its precision therapeutic development efforts. Its first step is improving both the accuracy of and accessibility to genomic testing for cancer patients,  In tandem, the company is in the clinic with its lead candidate seribantumab for cancer patients with a solid tumor of any origin that expresses a genomic change called an NRG1 fusion. On this episode of the Business of Biotech, Founder & CEO Shawn Leland, PharmD, RPh takes us inside the company's unique approach. 

In this episode of Occupation Station, 2008 ACPHS grad Shawn Leland talks about the personal, educational and professional ways he has been inspired to help people live longer, healthier lives. Some of that inspiration came to him through a clerkship rotation that didn't go as planned and instead landed him at Roswell Park Cancer Institute. While engaged in his studies, he was also seeing real health challenges in people he loved. He witnessed how important drug therapies were in helping them to live their best lives. After graduation, Leland says he experienced a big realization during a European Society of Medical Oncology conference and got an idea that led him to pull together the right researchers and financers to create a tumor agnostic drug development strategy. Even the name of Leland's company, Elevation Oncology, comes from a very inspired place. Leland has frequently been inspired along his career path; now he shares that inspiration with current and prospective ACPHS students.

Elevation Oncology has raised nearly $200M since its launch just two years ago. $200 million! That sounds like an enormous amount of investment capital, but when the company is potentially changing cancer treatment as we know it - you can see why investors are excited about Elevation's potential. Today, founder and CEO Shawn Leland tells us all about the raises, challenges, and excitement of growing his company. GIVEAWAY: Inspired by the Robbie Hardy episode where she shared the unbelievable story about how she used a magic 8-ball to help her decide whether or not to sell her company, we are giving away a Hutch 8-ball to anyone who writes a Founder Shares podcast review. All you need to do is write a review on Apple Podcasts or wherever you listen - and let us know by sending an email to podcast@hutchlaw.com.Hosted by Trevor Schmidt, Founder Shares is brought to you by Hutchison PLLC, and is edited and produced by Earfluence.

The presenting sponsor for today's episode is Elevation Oncology, elevating precision medicine to the forefront of every cancer treatment journey. On the show today, I welcome the esteemed Dr. Stephen Liu, Associate Professor of Medicine, Director of Thoracic Oncology, and Director of Developmental Therapeutics at Lombardi Comprehensive Cancer Center of Georgetown University. At a time when cancer treatment is more about your DNA and your RNA than where in your body cancer is — it's more important than ever to continue elevating the conversation about making biomarker testing a mandatory part of care. Why napalm everything if your genes make you eligible for a specific kind of therapy that's wayyyy better than proverbial napalm? NRG1 Fusion is an RNA test done on solid tumors — for the purposes of this episode Lung Cancer tumors — but this is a test that everyone with lung cancer needs to get out of the gate. You enter the "I have lung cancer store" and — BOOM — you get this test, which can make or break the trajectory of your care. From the seriousness of Phase II enrollment challenges to inane musings about Dartmouth, Boston Market, and the children's book The Three Billy Goats Gruff, strap in for a serious discussion about precision oncology and biomarker testing, especially if you or someone you know has lung cancer. For more information visit https://nrg1fusion.com/pod.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Dr. Stephen Liu, associate professor of medicine and director of Thoracic Oncology and Developmental Therapeutics at the Georgetown Lombardi Comprehensive Cancer Center, highlights key abstracts in lung cancer featured at the 2021 ASCO Annual Meeting.   Transcript:  ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Stephen Liu. He is an associate professor of medicine and the director of thoracic oncology and developmental therapeutics at the Georgetown Lombardi Comprehensive Cancer Center. Dr. Liu joins me to highlight advances in lung cancer featured at the 2021 ASCO Annual Meeting. Dr. Liu has served in a consulting or advisory role for Genentech, Pfizer, and AstraZeneca, among other organizations. His full disclosures and those relating to all episodes of the podcast are available on our transcripts at ASCO.org/podcasts. Dr. Liu, it's great to have you on the podcast today. Dr. Stephen Liu: Thanks for having me. ASCO Daily News: Dr. Liu, a lot of people were talking about the IMpower010 study during the annual meeting. That's abstract 8500, an interim analysis that showed really promising results for patients with resected non-small cell lung cancer. Can you tell us about this practice-changing study? Dr. Stephen Liu: Well, IMpower010 was a global randomized phase III trial, and I think this really was one of the highlights of the ASCO Annual Meeting from a lung cancer standpoint. As a reminder, our current standard of care is cisplatin-based chemotherapy for patients with resected stage II to III non-small cell lung cancer and for select patients with stage IB. We know from decades of experienced multiple phase III trials, large meta-analyses, that the risk of recurrence is quite high for resected stage II/III lung cancer. And the use of up to four cycles of cisplatin-based chemotherapy does lead to an improvement in survival, and that's our standard of care. That survival improvement, however, is modest, with an absolute improvement and 5-year survival of about 5%. And so we've been trying to improve outcomes in this setting for quite some time. We know from last year's ASCO that the subset of patients whose tumor harbors an EGFR mutation received some benefit from disease-free survival with the use of adjuvant osimertinib. IMpower010 presented at this year's ASCO by Dr. Heather Wakelee looks at the use of immunotherapy as a complementary adjuvant therapy. And we knew from press release that this study had met its primary endpoint. This was our first chance to look at the data first-hand and really see how it would impact practice. And I think the data were quite impressive. It's a fairly simple design. This study included patients with completely resected stage IB to IIIA non-small cell lung cancer, either histology. Note that this used AJCC version 7, and so the stage IB that were included had a size of at least four centimeters, and that's the subset that seems to derive the most benefit from chemotherapy. Now patients received cisplatin-based chemotherapy one to four cycles first. And those who received at least one cycle of chemotherapy were then randomly assigned 1 to 1 to receive 1 year of atezolizumab, PD-L1 inhibitor, or best supportive care. This was a large study, over 1,000 patients randomly assigned. It began enrollment in 2014. So it did include some EGFR and some ALK when maybe we didn't know quite as much about including those patients in these studies, but the EGFR was about 12%, the ALK was 3%. Some were unknown EGFR and ALK status, but these were likely the squamous histology, as those numbers line up. The PD-L1 testing, importantly, was done by the VENTANA SP263 assay, looking at tumor cell expression only, which is a fairly straightforward assay. And what we saw after a median follow up of almost 3 years was that in the primary high-risk population stage II to IIIA resected non-small cell lung cancer with the PD-L1 expression of at least 1%, the use of adjuvant atezolizumab significantly improved disease-free survival. And the hazard ratio there was 0.66. If we look at the 2-year disease-free survival (DFS) rate, it improved from 61% with best supportive care to 75%, and at 3-year DFS from 48% to 60%. So an improvement in the 3-year DFS rate and a hazard ratio of 0.66. The fourth plot showed that signal was greater in node-positive. As expected, no signal in that ALK subset, though it was small. But this is a pretty substantial improvement in disease-free survival. When we look at these Kaplan-Meier curves, they split immediately, really right at the first scan. And when we look at a study like this, this phase III trial, it reminds us how poor our current standard is; how many patients do suffer relapse and recurrence and death from this potentially curable cancer. Atezolizumab clearly improving outcomes in this subset. We then saw analyses of the resected stage II to III across PD-L1 strata, so positive and negative. And there the hazard ratio, as expected, less impressive, 0.79. If we look at the forest plot there, the hazard ratio for PD-L1 high, using that 50% cutoff we're used to, was substantial at 0.43. So overall, the DFS and PD-L1 positive 0.66 and the PD-L1 high 0.43. So no report on the PD-L1 low, which is what we're waiting for, that one at 49%, presumably not as impressive as 0.66. And we'll wait for those data to come out. But PD-L1 positive, a clear benefit. PD-L1 high, a substantial benefit. That's really where the formal analyses stopped. The stage IB to IIIA overall population was too immature for analysis, and overall survival was not yet formally tested. This will take a few years to breathe out. They did provide an early look at overall survival. And in that stage II to IIIA PD-L1 positive, there was the right trend, with a hazard ratio of 0.77, though not statistically significant. We did see these curves start to come apart at about 12 to 18 months, which is what you would expect if this study ultimately would lead out to be positive. We do want to wait for OS results. But one has to wonder, is a DFS benefit this substantial enough to change practice? And atezolizumab not yet approved in this setting, but the trial did meet its primary endpoint. And to me, for PD-L1 positive, and certainly for PD-L1 high, I do think these data aren't practice- changing. ASCO Daily News: Absolutely. Well, another trial that attracted a lot of attention was the CheckMate-816 trial. That's Abstract 8503. What can you tell us about the surgical outcome data reported in CheckMate-816? Dr. Stephen Liu: So CheckMate- 816 was a randomized phase III trial that looked at neoadjuvant therapy. So this also focused on resectable lung cancer. This is an area where we hope for cure, but for some of the more advanced stages, we don't necessarily expect it. Much room for improvement. We saw the IMpower010 data showing adjuvant immunotherapy improved DFS. Here we're looking at the neoadjuvant space. And at AACR in 2021, Dr. Patrick Forde presented some of the early PCR results. And that showed the pathologic complete response rates with neoadjuvant nivolumab plus chemotherapy for three cycles was superior to chemotherapy alone for three cycles. So the addition of nivolumab to chemotherapy improved the pathological CR rate from 2% to 24%. Really astounding. What Dr. Jonathan Spicer presented at ASCO 2021 were the surgical outcomes from that study. And we see that adding immunotherapy to chemotherapy significantly improves the pathologic CR rate. Does it come at a cost? Does it lead to more surgical complications? This is always a concern with neoadjuvant therapies. We've got someone in our clinic with a resectable lung cancer. If we mismanage that patient, we may lose the window for resection. So we always worry about delayed surgeries, canceled surgeries, more complicated surgeries. There have anecdotally been reports of increased perihilar fibrosis after neoadjuvant immunotherapy. Wouldn't that lead to longer, more complicated surgeries? And what we saw, frankly, was a bit surprising, for me. Surgery consistently easier, better in the experimental arm really across the board. The rates of going to surgery, completing surgery, 83% with nivolumab/chemotherapy, versus 75% with chemotherapy. So more patients going to surgery, fewer canceled surgeries. If we look at the type of surgery, minimally invasive surgery rates 30% with nivolumab/chemotherapy, [and] 22% with chemotherapy alone. Conversion to open thoracotomy was more common in the chemotherapy alone at 16%, the additional nivolumab 11%. And the complete R0 resection was achieved in 83% with nivolumab/chemotherapy, 78% with chemotherapy alone. Adverse events delayed surgery in six patients getting nivolumab and chemotherapy. It's important to watch that. But it was nine patients in getting chemotherapy alone. And if we look at the duration of surgery, and certainly there are many confounders in a statistic like this, but the surgery was shorter with nivolumab, certainly not lengthening the surgery. 184 minutes for nivolumab/chemotherapy, 217 [minutes] with chemotherapy alone. So these data are very reassuring to someone with a potentially resectable cancer. And I think that when I take a step back and look, maybe these results do make sense. Maybe this is what I should have expected. If we give a treatment that is more effective, that is a higher response rate, it works better. Those patients are less likely to have progressive disease, and the surgery should be more straightforward if there's less cancer to resect. So the CheckMate-816 surgical data, we've been waiting for this shoe to drop, and it was very reassuring. Perioperative immunotherapy is going to be an important part in the management of stage II/III non-small cell lung cancer in the years to come. Now going forward, we'll need to compare these adjuvant and neoadjuvant approaches and the relative merits of either strategy, but these results, I thought, were very reassuring. ASCO Daily News: Excellent. Well, moving on to the PACIFIC trial, Abstract 8511, this study reported improvements in 5-year overall survival and progression-free survival for unresectable stage III non-small cell lung cancer. What are your takeaways from this study? Dr. Stephen Liu: Sure. The PACIFIC study is a randomized phase III trial that's really set our standard of care for unresectable stage III locally advanced non-small cell lung cancer. This is a group where our standard of care, historically, has been concurrent chemoradiation, with the goal of cure, though, unfortunately, not necessarily the expectation, with recurrence rates quite high. We saw years ago the addition of 1 year of durvalumab improved progression-free survival, then ultimately improved overall survival compared to placebo. This was a fairly straightforward study. It enrolled unresectable stage III non--small cell lung cancer after chemoradiation, who did not have evidence of progression after completing therapy, to receive 1 year of durvalumab or placebo, a 2 to 1 randomization. The results markedly positive, leading to U.S. Food and Drug Administration (FDA) approval and really our new standard of care. These are long-term survival data, and it was presented by Dr. David Spigel. These are really important. Immunotherapy, the whole appeal of the strategy is the durability, the induction of memory T cells, meaningful long-term survival. Will this increase the rate of cure really is what we're going for. And when we saw the survival benefit with durvalumab, we knew that we were curing more patients. Long-term follow up is important to make sure that we don't have late recurrences, that we really are curing and not just delaying a recurrence for some patients. And in this analysis, with a 5-year follow up, we see durvalumab improve the median survival from 29 months with chemoradiation alone to 48 months with the addition of durvalumab. That's a hazard ratio of 0.72, 28% reduction in the risk of death, pretty substantial. That 5-year survival rate was 43% versus 33%. And importantly, these were very similar to the 4-year data that were presented by Dr. Corinne Faivre-Finn at World Conference in Lung Cancer, really very little drop off between year 4 and 5. And we refer to that as flattening of the tail, where the events are early, and at some point, they kind of stop happening. It's really what we want to see. While survival is what we hone in on, in an abstract like this, we also need to pay attention to progression-free survival (PFS). And the PFS rate at 5 years was 33% with durvalumab, versus 19% with chemoradiation alone. So 33% with no evidence of progression at 5 years. And if you are cured from lung cancer, then you can't have progression. So one in the three patients with no progression at 5 years, I think, is very reassuring, that PFS hazard ratio of 0.55. So prior to ASCO21, durvalumab was our standard of care. Now we just have longer term follow up to really solidify that choice. These are important data for patients and families to set expectations right, but our clear standard. Still, though, room for improvement in that 5-year PFS rate of 33%. We would like to see that higher, and ongoing strategies hopefully will help push that up. ASCO Daily News: Excellent. Some great survival data in the PACIFIC trial. Well, Abstract 9007 sparked a lot of interest as well. This is an expansion study of patritumab/deruxtecan in patients with EGFR-mutant non-small cell lung cancer. That's a difficult drug to pronounce, so I'm sure you'll do a better job. What can you tell us about this? Dr. Stephen Liu: Well, yeah, all these antibody drug conjugates do have tricky names, and so they are kind of fun to say. So patritumab/deruxtecan is a HER3 antibody drug conjugate. I suspect it will be better known as HER3-DXd, a little easier off the tongue. This was a study that looked at this agent in patients with EGFR-mutant non--small cell lung cancer after TKI therapy. And when we turn our attention to targeted agents, we have really transformative drugs with very wide therapeutic windows, little toxicity, very high efficacy, [and are] really game changers in patients with driver positive non--small cell lung cancer. But as we know, these treatments aren't cures. And we do expect resistance to osimertinib. The third generation TKI has been pretty heterogeneous. And once patients progress in osimertinib, the next standard therapy really is chemotherapy. And there's a bit of a drop off, with more toxicity, [and] less efficacy overall. So this remains an unmet need. Many studies are looking at different strategies there. We've seen the addition of MET inhibitors if MET is amplified for certain subtypes, RET, BRAF, for example, the addition of the targeted agents. This study, Abstract 9007 presented by Dr. Pasi Janne, looked at the HER3-DXd antibody drug conjugate. So patritumab/deruxtecan has a monoclonal antibody targeting HER3, a proprietary linker, and then a topoisomerase 1 warhead. And this was a phase I study that looked at 57 patients with EGFR-mutant lung cancer after TKI therapy mostly, but 90% were coming off of osimertinib. And what we saw, I thought, was very encouraging. This is a small, early study. These are very selective patients. But the response rate here almost 40%, disease control rate 72%, and the median progression-free survival with monotherapy of patritumab/deruxtecan was 8.2 months. These numbers may change as the studies get larger, but there's a clear signal of efficacy for patients who'd received chemotherapy before and then moved on to patritumab/deruxtecan. The response rate didn't really drop off, 37%. So even those that were more heavily pretreated, we're seeing a clear signal with response rates that really are higher than chemotherapy. What was, I think, most important, we saw efficacy of patritumab/deruxtecan across multiple different mechanisms of resistance. And so it wasn't one biomarker select. It really was active, very versatile agent. And really, I think that's what we need. While biomarker-driven resistance will be something we always hone in on and try to focus, we do need something that's much more versatile for rapid implementation. And this is having a lot of potential. [It was] very well tolerated. If we look at treatment-emergent adverse events, only one person stopped from a TEAE. Only 4% stopped due to TEAEs, so very well tolerated treatment. Response was also durable. One response listed was after 4 years of therapy, and so the potential for long-term disease control, long-term responses. So clearly an active drug. This is an area where we need a lot of drug development. Well tolerated, only 4% stopping due to adverse events and a nice signal of activity. Our next steps will be to make this a larger study to look in more patients to really hone in on the mechanisms and where this really is working. Can we widen that therapeutic index? And can we look at combinations? Is there a role to continue TKI with this, maybe for better CNS coverage or activity? That's what we'll see in the years to come. ASCO Daily News: Excellent. Well I'd like to ask you about a trial that you were involved in, the ARROW trial, Abstract 9089. Can you tell us about this impactful study? Dr. Stephen Liu: Yeah, sure. The ARROW trial is a study that I've been a co-investigator on for many years. This was presented by Dr. Giuseppe Curigliano. And this looks at a RET inhibitor called pralsetinib, originally when we first got involved called BLU-667. RET fusions are present in about 1% of non- small cell lung cancer. These are important events, because we know from other studies, such as the immunotarget registry led by Julien Mazieres,  that RET-positive lung cancers don't seem to respond as well to immunotherapy. However, in the past, the kinase inhibitors, the targeted agents we had the targeted RET, weren't very good. They had response rates around 30%, 40%, a lot of toxicity. These are drugs like vandetanib, cabozantinib. With the introduction of selective RET inhibitors, we've seen striking efficacy and much better tolerability. And we now have two approved RET inhibitors in this space--selpercatinib and pralsetinib--both receiving FDA accelerated approval based on their respective single arm studies. What we saw at ASCO 2021 from Dr. Curigliano was an update on the RET fusion positive lung cohort of ARROW. Again, this was a phase I/II trial looking at pralsetinib given at a dose of 400 milligrams by mouth once daily. We look at the patients with RET fusion-positive lung cancer. Now we just have longer follow up and more patients. And overall, the cohort exceeded 200 patients, so 216 patients for a pretty rare driver. And the response rate, 69%, very durable. The duration of response, 22 months. So really solidifying the efficacy and confirming the role in patients with RET fusion-positive lung cancer. If we break those data down a little bit, patients who had prior chemotherapy, which was 125 patients, response rate was 62%. The disease control rate, 91%. These responses are quick. The median time to responses is 1.8 months, so really that first scan. And that's what we see with targeted therapy. And we look at these waterfall plots, and I encourage you to take a peek at that. It's exactly what we want to see, the vast majority of patients, almost all patients, with some reduction and some with a quite substantial reduction. Again, the disease control rate after chemo was 91%. So really, the waterfall plot has that look that we seek for effective targeted therapy. The outcomes were even better in the first-line setting. Response rate originally 79% as first-line therapy. But the way the trial was originally written, it only included frontline patients who weren't eligible for chemotherapy for whatever reason. So that's going to be a more selective cohort. That was changed with an amendment. And once that was removed for people that were eligible for whatever frontline therapy you wanted to give, really our real world first line cohort, the response rate was 88%, disease control rate of 96%. So to think of a response rate in almost 90% of patients really gives us that confidence we want when we have a driver that we detect when we start a new agent. We're very confident that we're going to see efficacy in these drugs, very well tolerated, very few patients stopping due to a adverse event. A disease control rate of 96% in that first-line setting gives me the confidence to really use this in the first-line setting. ASCO Daily News: Absolutely. Well, as you know, the Annual Meeting this year focused on equity in cancer care. And there were a number of studies presented in the lung cancer space. I just wanted to get your thoughts on how this issue was addressed at the Annual Meeting in the lung cancer setting. I'm thinking of Abstract 9005 that looked at racial disparities. What are your thoughts on this issue? Dr. Stephen Liu: Yeah, this was an important abstract, I think. And the theme that Dr. Lori Pierce set of equity really was met by several different abstracts and was a recurrent focus for many important and really overdue discussions. Abstract 9005 was presented by Dr. Debora Bruno, and this really looked at disparities in biomarker testing. And we just talked about advances for EGFR-mutant lung cancer for RET fusion-positive non--mall cell lung cancer. We have many, many more, but we can only offer these agents if we know the target is present. And if we don't do proper biomarker testing, our care will not be optimal. If we don't know the molecular genotype of the cancer, we can't treat it properly. We are just guessing, and we're much more likely to deliver an ineffective therapy. We are potentially making subsequent therapies more dangerous. Knowing the right biomarker is critical to the proper management of non-small cell lung cancer. And if we don't have that, the outcomes will not be as good. The testing really is critical for the management of lung cancer. And what we saw from this abstract was there are disparities in how patients with non-small cell lung cancer are being tested, which simply isn't acceptable. This was a retrospective analysis that looked at Flatiron data, recent data, 2017 to 2020, a large data set, almost 15,000 patients with non-small cell lung cancer. Demographics were 66% white, 9% Black. If we look at biomarker testing specifically, patients who were Black were less likely to be tested, less likely to have proper biomarker testing, 73% versus 76%, less likely to have full next generation sequencing with a 10% difference, and less likely to get tested early. We know that testing really influences treatment from the jump right away. And if we don't have that information, our outcomes won't be as good. Our Black patients weren't being tested properly, weren't being tested in a timely manner. And more data showed that clinical trial participation was also decreased among Black patients, 4% involvement for white patients, 2% with Black patients. And these were actually very similar to what we saw in Abstract 9001 that was presented by Dr. Akinboro from the FDA. And that looked at patients who'd received chemoimmunotherapy. This was a pooled analysis looking at different PD-L1 cohorts. And what was noted on the demographics is that in the phase III registrational landmark studies, Black patients only represented about 2% of patients there as well. So strikingly similar numbers and a gross under-representation. It really is inexcusable and something we need to address. And we need to correct, because this is showing that our care is simply not up to par.  Trial participation is how we move the field, but many cases, especially in lung cancer, a field that moves so quickly, a clinical trial often represents the best possible option. And Black patients simply aren't enrolling in studies. And I think some of the disparities in clinical trial participation likely reflect some of the disparities in clinical trialists. And I think that if we continue to improve diversity in our workforce, in our oncology subspecialty, that'll be an important step into rectifying this. But this is something we need to look at critically. We need to assess all of our processes and think how we can do better today, and not tomorrow. ASCO Daily News: Absolutely. Thank you so much, Dr. Liu, for highlighting these really critical points and sharing your valuable insight on all of these impactful studies in lung cancer. Thank you so much. Dr. Stephen Liu: My pleasure. Thanks for having me. ASCO Daily News: And thank you to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. Stephen Liu Consulting or Advisory Role: Genentech, Pfizer, Lilly, Bristol-Myers Squibb, AstraZeneca, Takeda, Regeneron, G1 Therapeutics, Guardant Health, Janssen Oncology, MSD Oncology, Jazz Pharmaceuticals, Blueprint Medicines, Inivata, PharmaMar, Daiichi Sankyo/UCB Japan, BeiGene, Amgen, Turning Point Therapeutics, Elevation Oncology, and Novartis Research Funding (institution): Genentech/Roche, Pfizer, Bayer, Merck, AstraZeneca, Blueprint Medicines, Lilly, Rain Therapeutics, Alkermes, Bristol-Myers Squibb, Turning Point Therapeutics, RAPT, Merus, Elevation Oncology, and Erasca, Inc Travel, Accommodations, Expenses: AstraZeneca, Roche/Genentech, and MSD Oncology   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.