Clinical data presented today demonstrates the combination of tarlatamab with anti-PD-L1 therapy as first-line maintenance has an acceptable safety profile and resulted in unprecedented overall survival in patients with extensive-stage small cell lung cancer (ES-SCLC).
K.G. Paulson, MD, Providence-Swedish Cancer Institute, Seattle, Wash., presented new safety and efficacy data from the phase 1b DeLLphi-303 trial evaluating tarlatamab in combination with anti-PD-L1 therapy as first-line maintenance treatment for ES-SCLC at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC) in Barcelona, Spain.
Tarlatamab is a bispecific T-cell engager (BiTE®) immunotherapy designed to direct cytotoxic T cells to target and destroy cancer cells expressing delta-like ligand 3 (DLL3). Previous studies have shown tarlatamab prolongs overall survival in the second-line SCLC setting. In the DeLLphi-303 trial, investigators evaluated tarlatamab's safety and efficacy in the first-line maintenance setting in combination with either atezolizumab or durvalumab.
The phase 1b trial enrolled 88 patients with ES-SCLC who had completed 4–6 cycles of platinum-etoposide chemotherapy and anti-PD-L1 (unless unavailable) without disease progression. Within 8 weeks of the start of their last chemo-immunotherapy cycle, patients began maintenance treatment with tarlatamab (10 mg IV every two weeks) in combination with either atezolizumab (1680 mg IV every four weeks) or durvalumab (1500 mg IV every four weeks) until disease progression.
After a median follow-up of 18.4 months, the median overall survival (OS) was 25.3 months (95% CI, 20.3–not reached), and the median progression-free survival (PFS) was 5.6 months (95% CI, 3.5–9.0). The most common tarlatamab-related adverse event was cytokine release syndrome, occurring in 56% of patients-predominantly grade 1 in severity. Immune effector cell-associated neurotoxicity syndrome occurred in 6% of patients. Importantly, treatment-emergent and treatment-related adverse events decreased over time, demonstrating long-term tolerability.
The combination of tarlatamab with anti-PD-L1 therapy as first-line maintenance demonstrates a manageable safety profile and unprecedented overall survival in this patient population. These results support further evaluation of this combination in the active phase 3 DeLLphi-305 trial (NCT06211036) as a promising therapeutic strategy in first-line ES-SCLC."
K.G. Paulson, MD, lead investigator, Providence-Swedish Cancer Institute, Seattle, Wash.
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