Tarlatamab plus durvalumab (durva) vs durva as 1L maintenance (1LM) therapy following durva, platinum, and etoposide (1L durva + EP) in extensive-stage small cell lung cancer (ES-SCLC): Primary analysis of the phase 3 DeLLphi-305 trial

doi:10.1056/nejmoa2609482

DeLLphi-305

Patient / Population Intervention / Exposure Comparison Outcome

In patients with extensive-stage small cell lung cancer without progression after first-line durvalumab, platinum and etoposide, tarlatamab plus durvalumab maintenance improved overall survival compared with durvalumab alone.

N

563patients

Design

Phase 3 randomised (1:1) trial in 563 patients with extensive-stage small cell lung cancer without progression after first-line durvalumab, platinum and etoposide, comparing tarlatamab plus durvalumab (n = 282) with durvalumab alone (n = 281) as first-line maintenance until progression or unacceptable toxicity (NCT06211036).

Endpoint

Overall survival measured from randomisation.

ResultMedian OS 21.1 months (95% CI 20.8-NE) with tarlatamab plus durvalumab vs 12.7 months (95% CI 11.2-14.8) with durvalumab (HR 0.42; 95% CI 0.32-0.54; P < 0.001). 12-month OS rate 79.4% (95% CI 74.2-83.7) vs 53.3% (95% CI 47.3-59.0). Investigator-assessed median PFS 7.4 (95% CI 5.6-9.1) vs 1.9 months (95% CI 1.9-2.0) (HR 0.34; 95% CI 0.28-0.42; P < 0.001). ORR 26.4% (95% CI 20.9-32.5) vs 4.1% (95% CI 2.0-7.4) (P < 0.001). Grade ≥3 TEAEs occurred in 46.8% vs 40.6%. Cytokine release syndrome occurred in 49.6% vs 1.4% (grade ≥3 0.4% vs 0) and ICANS in 1.1% vs 0, with no fatal events.

Pérol M, Yoshida T, Ahn M, et al. N Engl J Med. 2026; published online 24 October. 10.1056/nejmoa2609482

Discussion & critique

This randomised phase 3 trial shows a large overall survival benefit from adding tarlatamab to durvalumab maintenance, supported by consistent gains in PFS and response. Median follow-up was 15.9 and 16.1 months and the upper confidence limit for median OS in the tarlatamab arm was not estimable, so the survival estimate is still immature. The abstract does not state whether the trial was blinded, PFS was investigator-assessed, and the comparator was durvalumab maintenance alone. Cytokine release syndrome affected about half of tarlatamab-treated patients, and the abstract does not report treatment discontinuations, subsequent therapies or subgroup results.