Work

Extended follow-up of tarlatamab in patients with small-cell lung cancer after platinum-based chemotherapy in the randomized phase III DeLLphi-304 study

Year: 2026

Type: article

Abstract: BACKGROUND: In the DeLLphi-304 trial, at a median follow-up of <12 months, tarlatamab significantly improved overall survival (OS; P < 0.001), progression-free survival (PFS; P = 0.002), and patient-reported outcomes (PROs), and demonstrated a favorable safety profile versus chemotherapy. We report efficacy and safety outcomes after extended follow-up in patients with small-cell lung cancer (SCLC). PATIENTS AND METHODS: In this phase III, open-label trial, patients with SCLC whose disease had progressed on or after platinum-based chemotherapy were randomly assigned (1 : 1) to receive either tarlatamab or chemotherapy (topotecan, lurbinectedin, or amrubicin) until disease progression, unacceptable toxicity, or death. The primary endpoint was OS. Secondary endpoints included investigator-assessed PFS, objective response, disease control, duration of response per RECIST v1.1, PROs, and safety. RESULTS: As of data cut-off (18 February 2026), median OS was 13.6 and 8.4 months with tarlatamab and chemotherapy, respectively (median follow-up, 23.3 and 22.8 months). Median PFS was 4.2 and 3.2 months, respectively (median follow-up, 22.2 and 21.9 months). Kaplan-Meier estimated OS rates at 12 and 24 months were 55.9% and 30.3% with tarlatamab versus 39% and 14.9% with chemotherapy; corresponding PFS rates at 12 and 24 months were 20.6% and 14.2% versus 5.9% and 2.3%. Objective response rate was 35.4% with tarlatamab, including six confirmed complete responses versus 20.4% with chemotherapy; at data cut-off, ongoing responses were observed in 31.1% (28 of 90) versus 3.8% (2 of 52) of responders, respectively. Sustained disease control for ≥52 weeks was observed in 24.4% versus 4.3%. Treatment-related adverse events (TRAEs) led to treatment discontinuation in 3.2% versus 6.6%; grade ≥3 events decreased over time, with no serious TRAEs with onset ≥12 months. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred early in treatment and were predominantly low grade. CONCLUSIONS: With extended follow-up, tarlatamab continues to demonstrate sustained and durable clinical benefit and a favorable long-term tolerability profile versus chemotherapy, in patients with SCLC after first-line platinum-based chemotherapy, supporting its use as the standard of care in this setting.

Source: Annals of Oncology

DOI: 10.1016/j.annonc.2026.10.095