Promising Results from DeLLphi-303: Safety and Survival in Extensive-Stage Small Cell Lung Cancer

Recent clinical findings from the Phase Ib DeLLphi-303 trial highlight the safety and efficacy of combining tarlatamab with anti-PD-L1 therapy as a first-line maintenance treatment for patients with extensive-stage small cell lung cancer (ES-SCLC). Presented by Dr. K.G. Paulson from the Providence-Swedish Cancer Institute at the 2025 WCLC in Barcelona, the study underscores significant advancements in survival outcomes for this patient group.

Tarlatamab is a bispecific T-cell engager designed to mobilize immune cells against cancer cells expressing delta-like ligand 3 (DLL3). Previous research demonstrated its potential to extend overall survival in second-line SCLC settings. Building on this, investigators assessed its safety and effectiveness when used alongside immune checkpoint inhibitors, atezolizumab or durvalumab, in the first-line maintenance phase.

The trial enrolled 88 patients who had previously responded to four to six cycles of platinum-etoposide chemotherapy combined with anti-PD-L1 therapy. Patients began maintenance therapy within eight weeks of completing chemotherapy, receiving tarlatamab intravenously every two weeks, combined with either atezolizumab or durvalumab every four weeks until disease progression.

After a median follow-up of 18.4 months, the median overall survival was an impressive 25.3 months, with median progression-free survival of 5.6 months. The safety profile was manageable, with cytokine release syndrome (predominantly grade 1) occurring in 56% of patients, and immune-related neurotoxicity in 6%. Importantly, adverse events decreased over time, indicating long-term tolerability.

Lead researcher Dr. Paulson emphasized, "The combination of tarlatamab with anti-PD-L1 therapy offers a promising and manageable approach, showing unprecedented survival in ES-SCLC patients." These promising results support the ongoing Phase III DeLLphi-305 trial, which aims to further validate this combination therapy as a standard first-line treatment option.

This breakthrough underscores the potential of innovative immunotherapy strategies to improve outcomes for patients with aggressive lung cancers.