Tarlatamab Plus Atezolizumab or Durvalumab as First-Line Maintenance for Patients With Extensive-Stage Small Cell Lung Cancer

According to results from the phase 1b DeLLphi-303 trial, first-line maintenance therapy with tarlatamab plus either atezolizumab or durvalumab demonstrated clinical promise among patients with extensive-stage small cell lung cancer (ES-SCLC). 

“Tarlatamab is a delta-like ligand 3 (DLL3)-directed bispecific T-cell engager immunotherapy that has improved survival in patients with previously treated [SCLC],” stated Kelly Paulson, MD, PhD, Providence-Swedish Cancer Institute, Seattle, Washington, and coauthors. “We evaluated the safety and activity of tarlatamab in combination with atezolizumab or durvalumab as first-line maintenance therapy in patients with [ES]-SCLC.” 

This non-randomized study enrolled 88 patients with ES-SCLC who did not experience disease progression after 4 to 6 cycles of platinum-etoposide chemotherapy plus a PD-L1 inhibitor. Patients received 10 mg of tarlatamab once every 2 weeks (after an initial dose of 1 mg) plus either 1680 mg of atezolizumab or 1500 mg of durvalumab once every 4 weeks until disease progression. The primary end point was safety. 

At a median follow-up of 18.4 months, the median time from the start of chemoimmunotherapy to the start of tarlatamab was 3.6 months and the median tarlatamab exposure was 35 weeks. The most common grade 3/4 adverse events included hyponatremia (10%), anemia (8%), and neutropenia (7%). Serious adverse events occurred in 57% of patients and most frequently included cytokine release syndrome (24%), pyrexia (7%), immune effector cell-associated neurotoxicity syndrome (5%), and pneumonia (5%). No treatment-related deaths were reported. The median OS was 25.3 months. 

“Tarlatamab plus a PD-L1 inhibitor as maintenance after first-line chemo-immunotherapy showed a manageable safety profile with promising anticancer activity, supporting the ongoing phase 3 trial,” concluded Dr Paulson et al. 

Source: 

Paulson KG, Lau SCM, Ahn MJ, et al. Safety and activity of tarlatamab in combination with a PD-L1 inhibitor as first-line maintenance therapy after chemo-immunotherapy in patients with extensive-stage small-cell lung cancer (DeLLphi-303): A multicentre, non-randomised, phase 1b study. Lancet Oncol. Published online: September 8, 2025. doi: 10.1016/S1470-2045(25)00480-2