Dr. Diwakar Davar and Dr. Jason Luke discuss advances in the neoadjuvant immunotherapy space that were presented at the 2024 ASCO Annual Meeting, including promising outcomes in high-risk melanoma from the NADINA trial, as well as other new treatment options for patients with advanced cancers.    TRANSCRIPT Dr. Diwakar Davar: Hello and welcome to the ASCO Daily News Podcast. I'm your guest host, Dr. Diwakar Davar, and I am an associate professor of medicine and the clinical director of the Melanoma Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. I am delighted to have my colleague and friend Dr. Jason Luke on the podcast today to discuss key late-breaking abstracts and advances in immunotherapy that were presented at the 2024 ASCO Annual Meeting. Dr. Luke is an associate professor of medicine, the associate director of clinical research, and the director of the Cancer Immunotherapeutic Center at the University of Pittsburgh Hillman Cancer Center.   You will find our full disclosures in the transcript of this episode.  Jason, it's always a pleasure to hear your insights on the key trials in these spaces and to have you back as a guest on this podcast that highlights some of the work, especially advances, that were just presented. Dr. Jason Luke: Well, thanks very much for the invitation. I always love joining the podcast. Dr. Diwakar Davar: We'll start very quickly by talking about some advances and really interesting things that happened both in the context of melanoma but also in immunotherapy in general. And we'll start with what I think was certainly one highlight for me, which was LBA2, the late-breaking abstract on the NADINA trial. It was featured in the Plenary Session, and in this abstract, Dr. Christian Blank and colleagues reported on the results of this phase 3 trial of neoadjuvant ipi-nivo. This is the flipped dose of ipi1/nivo3 versus adjuvant nivolumab in PD-1 naive, macroscopic, resectable, high-risk stage 3 melanoma.  By way of background, neoadjuvant immunotherapy for those listening is an area of increasing interest for drug developers and development for both approved and novel agents. Neoadjuvant immunotherapy has been studied with multiple approved agents, including PD-1 monotherapy, PD-1 LAG-3, PD-1 CTLA-4, T-VEC, as well as investigational agents and multiple randomized and non-randomized studies. The benchmark pathologic response rates with these agents range from 17% PCR with PD-1 monotherapy, 45% to 55% PCR with PD-1 CTLA-4 combination therapy, and slightly higher 57% PCR with PD-1 LAG-3 has recently reported by Dr. Rodabe Amaria from MD Anderson. However, as we embark on phase 3 comparisons for various neoadjuvant compared to adjuvant immunotherapy trials and combinations, we're increasingly moving towards event-free survival as the primary endpoint for neoadjuvant versus adjuvant studies. And this was most recently studied in the context of SWOG S1801, a study that was led by Dr. Sapna Patel.  So, Jason, before we start on NADINA, can you briefly summarize the SWOG S1801 trial and the event-free survival statistic reported by Dr. Patel and her colleagues? Dr. Jason Luke: Well, absolutely. And these data were reported at ESMO about two years ago and then in the New England Journal last year. The S1801 study answered a very simple question: What would happen if you took three of the doses of standard adjuvant therapy with pembrolizumab and moved them prior to surgery? And on a high level, the study is as simple as that. And many of us were somewhat skeptical of this trial design because we thought that just moving the doses earlier may not actually have a major impact.  In the study, you alluded to the event-free survival statistic, and that alludes to what was considered an event. And so, without reading all of it, there were several different aspects that were included in terms of time, based on the date of randomization until the first of a series of e