Multinational phase 3 trial of tarlatamab-durvalumab maintenance for extensive-stage small cell lung cancer

Patients with extensive-stage small cell lung cancer (ES-SCLC) have poor outcomes, with a median overall survival of approximately 12 months. Tarlatamab (bispecific T-cell engager targeting DLL3 and CD3) was previously shown to improve survival as second-line therapy. The multinational phase 3 DeLLphi-305 trial investigated addition of tarlatamab to durvalumab maintenance therapy for ES-SCLC without progression after initial chemoimmunotherapy. Results of a prespecified interim analysis have now been reported. A total of 563 patients were randomized to receive tarlatamab-durvalumab (n=282) or durvalumab alone (n=281). At a median follow-up of 15.9 months in the tarlatamab-durvalumab group and 16.1 months in the durvalumab group, the estimated median overall survival was 21.1 months with tarlatamab-durvalumab versus 12.7 months with durvalumab (HR 0.42; p<0.001); the median progression-free survival was 7.4 months versus 1.9 months (HR 0.34; p<0.001). Adverse events of grade 3 or higher occurred in 46.8% of the patients who received tarlatamab-durvalumab and 40.6% or those who received durvalumab alone. Cytokine release syndrome, mainly grade 1 or 2, was seen in nearly half of the patients receiving tarlatamab-durvalumab. The authors conclude that addition of tarlatamab to durvalumab maintenance therapy resulted in significantly longer overall survival and progression-free survival among patients with ES-SCLC.