Adding tarlatamab to durvalumab maintenance produced a statistically significant and clinically meaningful improvement in overall survival in extensive-stage small cell lung cancer (ES-SCLC), Amgen (Nasdaq: AMGN) reported September 8, marking the first Phase III bispecific T-cell engager trial to demonstrate an OS benefit in the first-line maintenance setting for this disease.
The result comes from the Phase III DeLLphi-305 trial, a global, randomized, open-label study enrolling 563 patients who had not progressed following induction with durvalumab, platinum-based chemotherapy and etoposide. Patients were randomized 1:1 to tarlatamab plus AstraZeneca's Imfinzi (durvalumab) or durvalumab alone. The trial met its primary OS endpoint at a pre-specified interim analysis, and also demonstrated statistically significant improvements in progression-free survival and objective response rate. Numerical data — including median OS, hazard ratios and p-values — were not disclosed; Amgen said detailed results will be presented at an upcoming medical congress.
Tarlatamab is a DLL3 × CD3 bispecific T-cell engager that redirects cytotoxic T cells to DLL3-expressing SCLC tumor cells. DLL3 is expressed on the surface of SCLC cells in approximately 85–96% of patients but is minimally expressed on healthy tissue. The combination with durvalumab, an anti-PD-L1 checkpoint inhibitor, pairs direct T-cell redirection with checkpoint release — two mechanistically distinct immune activation strategies.
Tarlatamab is already approved in the US for adults with ES-SCLC whose disease has progressed on or after platinum-based chemotherapy, a status that was converted from accelerated to full approval in November 2025 on the strength of the Phase III DeLLphi-304 trial, which showed a 40% reduction in the risk of death and a median OS of 13.6 versus 8.3 months compared with standard-of-care chemotherapy. The DeLLphi-305 data, if the magnitude of benefit is confirmed at congress presentation, would support a regulatory submission for a new first-line maintenance indication — a substantially larger addressable population, given that only approximately 40% of ES-SCLC patients currently reach second-line therapy.
The safety profile of tarlatamab plus durvalumab was described as consistent with the known profiles of each agent individually, with no new or unexpected signals identified. The known toxicity profile for tarlatamab includes cytokine release syndrome (CRS) in 57% of patients in the pooled monotherapy safety population, with Grade 3 or higher events in approximately 2% and immune effector cell-associated neurotoxicity syndrome (ICANS) in 10%.