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Two major phase 3 trials presented at ESMO 2026 cement tarlatamab as the new standard of care for extensive-stage small cell lung cancer (ES-SCLC). Extended follow-up from DeLLphi-304 confirmed durable survival in the second-line setting, while DeLLphi-305 showed that adding tarlatamab to durvalumab as first-line maintenance nearly doubled median overall survival compared to durvalumab alone — prompting a standing ovation from the ESMO audience.
Two landmark phase 3 trials presented at the 2026 ESMO Congress in Madrid are reshaping how extensive-stage small cell lung cancer (ES-SCLC) is treated — and the results are turning heads across oncology.
DeLLphi-304 (second-line): Extended follow-up at a median of 23.3 months confirmed that tarlatamab (Imdelltra) continues to outperform chemotherapy after first-line platinum-based therapy. Median overall survival was 13.6 months vs. 8.4 months with chemo, and 30% of tarlatamab patients were alive at 24 months vs. just 15% on chemo. Crucially, toxicity didn't worsen with longer treatment — side effects like cytokine release syndrome (CRS) peaked early and faded over time.
DeLLphi-305 (first-line maintenance): Adding tarlatamab to durvalumab after induction chemoimmunotherapy cut the risk of death by 58% and nearly doubled median OS to 21.1 months vs. 12.7 months with durvalumab alone — the longest median OS ever reported in first-line ES-SCLC. The data, published simultaneously in the New England Journal of Medicine, drew a standing ovation at ESMO.
By the Numbers:
Why it matters: SCLC has long been one of oncology's toughest challenges, with rapid relapse and historically poor survival. These two trials — covering both the maintenance and second-line settings — establish tarlatamab as a cornerstone of ES-SCLC treatment and offer patients what experts are calling "real, credible hope in a disease where hope has been in short supply."
