Tarlatamab in small cell lung cancer following platinum-based chemotherapy: subgroup analysis of Japanese patients from the DeLLphi-304 study

Abstract Background In the Phase 3 DeLLphi-304 trial, tarlatamab significantly improved overall survival (OS) over chemotherapy for small-cell lung cancer (SCLC) progressed after platinum-based chemotherapy. We report efficacy and safety in the Japanese subpopulation. Methods Patients were randomized to tarlatamab or amrubicin in Japan. The primary endpoint was OS. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and safety. Results As of 29 Jan 2025 (data cutoff), 35 patients (tarlatamab, n = 12; amrubicin, n = 23) were enrolled. Baseline characteristics were generally balanced although fewer tarlatamab-treated patients had chemotherapy-free interval < 90 days or brain metastases. Median OS was NE (95% CI, 10.4, NE) for tarlatamab versus 11.5 (6.2, NE) months for amrubicin (HR [95% CI] = 0.533 [0.186, 1.529]). Twelve-month survival was 66.7% (33.7, 86.0) versus 47.0% (25.7, 65.6), respectively. Median PFS was 4.0 (1.3, 11.3) months versus 4.2 (2.1, 5.4) months (HR [95% CI] = 0.726 [0.339, 1.554]). ORR was 33.3% (9.9, 65.1) versus 26.1% (10.2, 48.4). Median DOR was 10.1 (3.0, NE) months versus 5.6 (2.8, NE) months. Grade ≥ 3 treatment-related adverse events were less frequent with tarlatamab (8.3%) versus amrubicin (56.5%). Cytokine release syndrome occurred in 75% of tarlatamab-treated patients (all were grade 1 or 2) and grade 2 immune effector cell-associated neurotoxicity syndrome was reported in 1 (8.3%) patient. Conclusion Tarlatamab demonstrated numerically longer OS and DOR, and higher ORR versus amrubicin in Japanese patients with SCLC, with fewer high-grade treatment-related adverse events. These results in Japanese patients support those of the global population.