A post-hoc analysis from the phase 3 DeLLphi-304 trial shows that second-line tarlatamab significantly improved efficacy and safety compared with standard chemotherapy among patients with small cell lung cancer (SCLC). 

These findings were presented by Pedro Simoes da Rocha, Hospital del Mar Research Institute, Barcelona, Spain, at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany. 

This study randomized 509 patients on a 1-to-1 basis to receive either tarlatamab (n = 254) or standard chemotherapy (topotecan, lurbinectedin, or amrubicin; n = 255). Subgroups were defined by chemotherapy-free interval (CFI; < 90 days or ≥ 90 days) and prior anti-PD-L1 use. Key end points included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety.

Median OS was 10.9 months in the tarlatamab arm and 6.4 months in the chemotherapy arm among patients with a CFI of < 90 days and 17.1 months and 10.6 months, respectively, among patients with a CFI of ≥ 90 days. Median PFS was 3.2 months in the tarlatamab arm and 2.7 months in the chemotherapy arm among patients with a CFI of < 90 days and 4.5 months and 4.4 months, respectively, among patients with a CFI of ≥ 90 days. The ORR was 33% in the tarlatamab arm and 10% in the chemotherapy arm among patients with a CFI of < 90 days and 37% and 29%, respectively, among patients with a CFI of ≥ 90 days. 

Median OS was 14.1 months in the tarlatamab arm and 8.3 months in the chemotherapy arm among patients who received a prior anti-PD-L1 inhibitor and 13.6 months and 8.3 months, respectively, among patients who were anti-PD-L1 inhibitor-naïve. Median PFS was 4.2 months in the tarlatamab arm and 3.5 months in the chemotherapy arm among patients who received a prior anti-PD-L1 inhibitor and 3.6 months and 3.8 months, respectively, among patients who were anti-PD-L1 inhibitor-naïve. The ORR was 38% in the the tarlatamab arm and 20% in the chemotherapy arm among patients who received a prior anti-PD-L1 inhibitor and 28% and 21%, respectively, among patients who were anti-PD-L1 inhibitor-naïve.

In patients with a CFI <90 days, grade ≥3 treatment-related adverse events were reported in 30% of patients in the tarlatamab arm and 58% in the chemotherapy arm. Treatment-related dose modifications were reported in 21% and 50% of patients, respectively. In patients with a CFI of ≥ 90 days, grade ≥3 treatment-related adverse events were reported in 24% of patients in the tarlatamab arm and 66% of patients in the chemotherapy arm. Treatment-related dose modifications were reported in 18% and 59% of patients, respectively. Similar trends were observed by prior anti-PDL-1 status with grade ≥3 treatment-related adverse events reported in 26% and 59% of patients who received a prior anti-PD-L1 inhibitor and 29% and 69% of patients who were anti-PD-L1 inhibitor-naïve. Rates of cytokine release syndrome with tarlatamab were stable across subgroups, occurring in 51% and 59% of patients, and were reported as manageable.

Second-Line tarlatamab “exhibited superior survival outcomes and lower rates of both high-grade [treatment-related adverse events] and treatment modifications compared to [standard chemotherapy], regardless of CFI status or prior anti-PD-L1 use,” concluded Dr Simones de Rocha. “In contrast to [standard chemotherapy], the reduced risk of death and higher ORR with tarlatamab remained consistent even in platinum-resistant disease where prognosis has been especially poor, reinforcing tarlatamab as a standard of care.” 

Source:

Simoes da Rocha PF, Sun L, Cho BC, et al. Tarlatamab as second-line (2L) treatment for small cell lung cancer (SCLC): Outcomes by chemotherapy-free interval (CFI) and prior PD-(L)1 inhibitor use in the phase III DeLLphi-304 trial. Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. LBA101