Tarlatamab CD3×DLL3 T-cell engager lifts median OS to 13.6 mo after platinum-relapsed SCLC

Tarlatamab is a bispecific that redirects T cells to DLL3-positive neuroendocrine cells. In the phase 3, open-label DeLLphi-304 trial (NCT05740566) 509 small-cell lung cancer patients who had progressed on platinum chemotherapy were randomised to tarlatamab (n = 254) or chemotherapy (n = 255). Median overall survival reached 13.6 months with tarlatamab versus 8.3 months with chemotherapy (HR 0.60, 95% CI 0.47-0.77; P<0.001). Grade ≥3 adverse events were lower (54% vs 80%), and only 5% discontinued treatment (vs 12%). Standard second-line regimens historically deliver 5-10 mo OS—topotecan ~5-8 mo and lurbinectedin ~8-10 mo—highlighting the survival edge and cleaner safety profile seen here.