Amgen: IMDELLTRA plus IMFINZI cuts death risk 58% in first‑line maintenance ES‑SCLC

Study and publication

DeLLphi‑305 is a global randomized Phase 3 trial comparing IMDELLTRA (tarlatamab‑dlle) plus durvalumab versus durvalumab alone as first‑line maintenance for extensive‑stage small cell lung cancer (ES‑SCLC) in patients who had not progressed after durvalumab plus platinum‑etoposide induction. Results were presented at the ESMO Presidential Symposium and published in The New England Journal of Medicine.

Efficacy

At a median follow‑up of ≈16 months the combination reduced the risk of death by 58% (HR 0.42; 95% CI: 0.32–0.54) and extended median overall survival to 21.1 months versus 12.7 months with durvalumab alone. One‑year survival was nearly 80% versus 53%. At a median follow‑up of 13.9 months the combination reduced risk of progression or death by 66% (PFS HR 0.34) with median PFS 7.4 versus 1.9 months. Objective response rate was 26.4% versus 4.1%.

Safety

Grade 3 or higher treatment‑related adverse events occurred in 20.9% of patients on the combination and 10.8% on durvalumab alone; most frequent Grade ≥3 events included decreased neutrophil count, decreased appetite, neutropenia, asthenia and weight loss. Cytokine release syndrome was reported in 49.6% of patients receiving IMDELLTRA, predominantly Grade 1–2, with one Grade 3 event and no Grade ≥4 events. Immune effector cell‑associated neurotoxicity syndrome occurred in 1.1% with no Grade ≥3 events.

Additional data and next steps

Updated DeLLphi‑303 (Phase 1b) follow‑up showed median OS of 37.9 months from start of first‑line maintenance with IMDELLTRA plus anti‑PD‑L1 therapy (median follow‑up 30.8 months) and 58.1% two‑year survival. DeLLphi‑304 (second‑line) reported OS 13.6 versus 8.4 months (HR 0.62). Amgen indicated plans to engage regulatory authorities and presented these data at ESMO 2026.