ESMO 2026: New insights into tarlatamab for ES-SCLC
DeLLphi-305 and beyond
Key takeaways:
• Tarlatamab plus durvalumab reduced the risk of death by 58% versus durvalumab alone as 1LM in ES-SCLC
• Median OS improved from 12.7 to 21.1 months, with significant improvements in PFS and ORR
• CRS was common but predominantly low grade; no fatal CRS or ICANS events occurred
At the Presidential Symposium I of the European Society for Medical Oncology (ESMO) Congress 2026, Jacob Sands (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) presented the primary analysis of the phase 3 DeLLphi-305 trial. The results were concurrently published in the New England Journal of Medicine (NEJM).
The DeLLphi-305 trial randomized 563 patients with extensive-stage small-cell lung cancer (ES-SCLC) whose disease had not progressed following first-line durvalumab plus platinum–etoposide to tarlatamab plus durvalumab (n=282) or durvalumab alone (n=281) as first-line maintenance (1LM) therapy. Treatment continued until disease progression or unacceptable toxicity. Overall survival (OS) was the primary endpoint, with investigator-assessed progression-free survival (PFS) as a key secondary endpoint.
What were the key findings from DeLLphi-305?
We do this work not to improve everybody’s survival by a few months, but to improve it by years.
Tarlatamab plus durvalumab significantly improved OS compared with durvalumab alone. Median OS was 21.1 months versus 12.7 months, corresponding to a 58% reduction in the risk of death (HR, 0.42; 95% CI, 0.32–0.54; P<0.001). At 12 months, OS rates were 79.4% and 53.3%, respectively.At a median follow-up of 13.9 months, median PFS was 7.4 months in the tarlatamab plus durvalumab group versus 1.9 months in the durvalumab-alone group (HR, 0.34; 95% CI, 0.28–0.42; P<0.001). Objective response rates (ORR) were 26.4% and 4.1%, respectively (P<0.001).
Grade ≥3 treatment-emergent adverse events occurred in 46.8% of patients receiving tarlatamab plus durvalumab and 40.6% receiving durvalumab alone. Cytokine release syndrome (CRS) occurred in 49.6% of the combination group but was predominantly low grade, with grade ≥3 CRS reported in 0.4%. Immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 1.1%, with no grade ≥3 events. No fatal CRS or ICANS events occurred.
Jacob Sands concluded “DeLLphi-305 has demonstrated unprecedented outcomes in both median [OS] and median [PFS]… all with a toxicity profile that appears manageable” and that the findings support tarlatamab plus durvalumab “as a new standard of care in the treatment of [ES-SCLC]”
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