Extensive-stage small cell lung cancer (ES-SCLC) remains one of the most aggressive thoracic malignancies, typically diagnosed at an advanced stage and with limited treatment options.1 Tarlatamab, a DLL3-directed bispecific T-cell engager immunotherapy, has been shown to improve survival in patients with previously treated SCLC.
A recent study, presented by Kelly Paulson, MD, PhD, at the 2025 World Conference on Lung Cancer (WCLC), reported on the safety and efficacy of tarlatamab in combination with a PD-L1 inhibitor as first-line maintenance therapy after chemo-immunotherapy for patients with ES-SCLC. Dr. Paulson leads the Center for Immuno-Oncology at the Paul G. Allen Research Center and is an Assistant Professor at the Elson S. Floyd College of Medicine at Washington State University.
The session titled Optimizing Front-Line Treatment in SCLC is available on demand to registered WCLC 2025 attendees.
Study Background and Methods
The multicenter, non-randomized, phase 1b study, known as DeLLphi-303, included 88 patients with ES-SCLC who did not experience disease progression after receiving four to six cycles of platinum-etoposide chemotherapy, combined with a PD-L1 inhibitor. Within 8 weeks following the start of their last chemo-immunotherapy (chemo-IO) cycle, patients received either tarlatamab (10 mg intravenously every 2 weeks) plus atezolizumab (1680 mg intravenously once every 4 weeks) or tarlatamab in combination with durvalumab (1500 mg intravenously once every 4 weeks) as first-line maintenance therapy until disease progression..2
The primary endpoints included dose-limiting toxicities, treatment-emergent adverse events (TEAEs), and treatment-related adverse events (TRAEs).2
All patients who received at least one dose of tarlatamab were included in this evaluation. The secondary endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and disease control.
Key Findings
The median follow-up was 18.4 months from the start of maintenance among the 88 patients enrolled, with a median exposure to tarlatamab of 35 weeks. Dr. Paulson said the combination of tarlatamab plus a PD-L1 inhibitor demonstrated encouraging efficacy, with a median OS of 25.3 months (95% CI, 20.3-not reached) and the median PFS of 5.6 months (95% CI, 3.5–9.0). After completion of first-line chemo-IO, the overall response rate (ORR) was 24% and the median duration of response (DOR) was 16.6 months.2
The most common TRAE was cytokine release syndrome in 56% of patients. Immune effector cell-associated neurotoxicity syndrome occurred in 6% of patients. However, TRAEs decreased over time, which proves the long-term tolerability of the treatment regimen.2
“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,” Dr. Paulson said.
References
- 1. Damiano P, Stefani A, Avancini A, Belluomini L, Bria E, Pilotto S. Real-world evidence in extensive disease small cell lung cancer: The missing piece of the puzzle. Crit Rev Oncol Hematol. 2025;207:104618. doi:10.1016/j.critrevonc.2025.104618
- 2. 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. 2025;26(10):1300-1311. doi:10.1016/S1470-2045(25)00480-2
