Extended follow-up of tarlatamab in patients with small-cell lung cancer after platinum-based chemotherapy in the randomized phase 3 DeLLphi-304 study

Abstract

Background In the DeLLphi-304 trial, at a median follow-up of <12 months, tarlatamab significantly improved overall survival (OS), progression-free survival (PFS), 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 3, open-label trial, patients with SCLC whose disease had progressed on or after platinum-based chemotherapy were randomized (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 cutoff (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 12/24 months were 55.9%/30.3% with tarlatamab versus 39.0%/14.9% with chemotherapy; corresponding PFS rates at 12/24 months were 20.6%/14.2% versus 5.9%/2.3%. Objective response rate was 35.4% with tarlatamab, including six confirmed complete responses versus 20.4% with chemotherapy; at data cutoff, ongoing responses were observed in 31.1% (28/90) versus 3.8% (2/52) of responders, respectively. Sustained disease control for ≥52 weeks was observed in 24.4% versus 4.3%. Treatment-related adverse events led to treatment discontinuation in 3.2% versus 6.6%; grade ≥3 events decreased over time, with no serious TRAEs with onset ≥12 months. CRS and ICANS 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.