ASCO 2026 | Lung cancer at ASCO 2026: LIBRETTO-432, DeLLphi-304 & ALCHEMIST

There’s a lot of interesting things happening as far as lung cancer is concerned in this year’s ASCO, particularly in the early-stage lung cancer setting and the small cell lung cancer track. There is at least three abstracts that I feel are of high clinical relevance and importance. One is the CNS, Central Nervous System Activity Efficacy of Tarlatamab, which is a bispecific T-cell engager, gained full FDA approval last year, November of 2025. And in fact, last year, DeLLphi-304 was the phase three trial that was presented comparing Tarlatamab to second-line chemotherapy, which resulted in this full FDA approval. And this year, one of the presentations is on the CNS efficacy of tarlatamab, where they had around 250 patients in each arm and around 50 to 60 patients in the tarlatamab arm versus a chemotherapy arm had baseline brain metastasis with follow-up scans. And in this study, they did show that there was disease-free survival benefit, CNS progression-free survival benefit, as well as intracranial activity of tarlatamab. In both patients that had previous treatment, that is SRS or stereotactic radiosurgery, as well as around 25% of patients in the cohorts that were being compared did not have any previous treatment, suggesting that tarlatamab does have intracranial activity and benefit in these patients. And it actually raises the bar for patients with small cell lung cancer who have baseline brain metastasis. So this is very practice-informing. We’re already using it in the clinical setting. But I think seeing the CNS benefit of tarlatamab through this post hoc analysis of Delphi 304 is going to make it even more important to choose tarlatamab as the optimal choice of treatment for patients with small cell lung cancer. There are also studies that are being presented which are being evaluated in the earlier stage small cell setting where tarlatamab is being used. So more results to watch out for there. The second study that I feel is, again, very interesting and important is the plenary study that is being presented by Dr. Goldman on the adjuvant selpercatinib in RET fusion positive early-stage non-small cell lung cancer. So RET fusions, these are fusions that are present in only one to two percent of non-small cell lung cancer. So they’re rare, but they’re very actionable. Currently, we have two FDA approvals, that is selpercatinib as well as pralsetinib in the advanced non-small cell lung cancer setting, both in the first line as well as second line and beyond. But what this trial is doing is in the early-stage setting, they’re looking at whether selpercatinib offers disease-free survival benefit compared to standard chemotherapy. And as expected, which we have also seen in the earlier stage setting with EGFR inhibitors such as osimertinib or alectinib in stage 1 to 3a non-small-cell lung cancer. Similarly, selpercatinib does show disease-free survival benefit in this setting, which again is practice-changing. And more importantly, this tells us that NGS sequencing is going to become integral in treating patients appropriately with precision medicines to improve outcomes. The third study, which interestingly is a negative trial, which is the ECOG-ACRIN adjuvant nivolumab clinical trial being presented by Dr. Chaft, it questions the relevance of adjuvant immunotherapy in early-stage non-small cell lung cancer. So in the last couple of years, we’ve seen some major approvals in the neoadjuvant perioperative setting for early-stage non-sponsored lung cancer, such as Checkmate 816, which was presented last year with an overall survival benefit, as well as the Keynote 671 with an overall survival benefit. And there’s adjuvant atezolizumab, which is also approved. But the ECOG-ACRIN study, which was in fact started, the concept developed early on before some of these trials, other trials were reported, but had a co-primary endpoint of disease-free survival in the intention to treat population as well as the PD-L1 more than 50% population. And it was negative for both. But I do think this trial teaches us some important aspects around the utility of adjuvant therapies. And it basically suggests that one size does not fit all, biology as well as context matters. And there’s a lot to learn in terms of contribution of effect in the perioperative setting. So if we give neoadjuvant chemoimmunotherapy followed by surgery and followed by adjuvant immunotherapy, the question that this study begets is that the adjuvant portion actually adds much in the setting of early-stage non-small cell lung cancer. So a lot to learn there. I think there’s interesting studies in early-stage being presented as far as ctDNA is also concerned and their utility as far as MRD and continuing patients on certain therapies. So I think some of these abstracts highlight both how the drug development space is shaping up as well as questions the notion of placing all patients into one bucket, which cannot be something that we can make further developments with. So we have to basically choose our treatments based on the context, the biology, as well as what matters for the patients.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.