According to primary analysis results from the DeLLphi-304 trial, tarlatamab, a bispecific T-cell engager, significantly improved outcomes compared to chemotherapy among previously treated patients with small cell lung cancer (SCLC). 

These data were first presented by Charles Rudin, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, New York, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. 

In this study, 509 patients who experienced disease progression on or after platinum-based chemotherapy were randomized on a 1-to-1 basis to receive either tarlatamab (n = 254) or chemotherapy with topotecan, lurbinectedin, or amrubicin (n = 255). Patients were stratified based on prior treatment with a PD-L1 inhibitor, chemotherapy-free interval, presence of brain metastases, and intended chemotherapy regimen. The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS), objective response rate (ORR), duration of response, disease control rate, and safety. 

At analysis, median OS was 13.6 months in the tarlatamab arm and 8.3 months in the chemotherapy arm (hazard ratio [HR] 0.60; 95% confidence interval [CI], 0.47 to 0.77; P < .001) and median PFS was 4.2 months and 3.2 months (HR 0.72; 95% CI, 0.59 to 0.88; P < .001), respectively. The ORR was 35% in the tarlatamab arm and 20% in the chemotherapy arm. Median duration of response was 6.9 months in the tarlatamab arm and 5.5 months in the chemotherapy arm and disease control rate was 68% and 64%, respectively. 

Grade ≥3 treatment-related adverse events occurred in 27% of patients in the tarlatamab arm and 62% of patients in the chemotherapy arm. The most common events included neutropenia and lymphopenia in the tarlatamab arm and anemia and neutropenia in the chemotherapy arm. Treatment-related adverse events led to treatment discontinuation in 3% of patients in the tarlatamab arm and 6% of patients in the chemotherapy arm. 

“The DeLLphi-304 trial showed tarlatamab significantly improved OS [and] PFS … with a favorable safety and tolerability profile compared to [chemotherapy] in [patients] with SCLC that progressed on or after initial platinum-based [chemotherapy], defining a new standard of care for these patients,” concluded Dr Rudin et al. 

Source: 

Rudin C, Mountzios G, Sun L, et al. Tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): Primary analysis of Ph3 DeLLphi-304. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract LBA8008