FDA Approves Tarlatamab for Extensive-Stage Small Cell Lung Cancer
Key Clinical Takeaways
- Clinical Relevance: The FDA has approved tarlatamab for the treatment of patients with extensive-stage small cell lung cancer who experience disease progression on or after platinum-based chemotherapy.
- Design/Population: In the phase 3 DeLLphi-304 trial, 509 patients who experienced disease progression or or after chemotherapy with or without an anti-PD-L1 antibody were randomized 1:1 to receive either tarlatamab or investigator’s choice standard chemotherapy.
- Key Outcomes: At analysis, tarlatamab improved both OS (HR 0.60; 95% CI, 0.47 to 0.77; P < .001) and PFS (HR 0.72; 95% CI, 0.59 to 0.88; P < .001). Tarlatamab also improved dyspnea scores. Close monitoring for CRS, ICANS, and other immune-related toxicities is essential for safe administration.
On November 19, 2025, the US Food and Drug Administration (FDA) granted traditional approval to tarlatamab for the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) who experience disease progression on or after platinum-based chemotherapy. In 2024 tarlatamab had received accelerated approval for this indication, and this conversion to traditional approval was based on results from the phase 3 DeLLphi-304 trial.
In this multicenter, open-label trial, 509 patients who experienced disease progression or or after chemotherapy with or without an anti-PD-L1 antibody were randomized 1:1 to receive either tarlatamab or investigator’s choice standard chemotherapy (topotecan, lurbinectedin, or amrubicin) until disease progression or unacceptable toxicity. The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS), 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). Median PFS was 4.2 months and 3.2 months, respectively (HR 0.72; 95% CI, 0.59 to 0.88; P < .001). Tarlatamab significantly improved dyspnea scores at week 18 compared to standard chemotherapy.
The recommended dose of tarlatamab is 1 mg on cycle 1, day 1 followed by 10 mg on days 8, 15, and every 2 weeks thereafter until disease progression or unacceptable toxicity.
The prescribing information includes a Boxed Warning for life-threatening or fatal cytokine release syndrome (CRS) and neurologic toxicities including immune effector cell-associated neurotoxicity syndrome (ICANS). Additional warnings and precautions include cytopenias, infections, hepatotoxicity, hypersensitivity, and embryo-fetal toxicity.
Source:
US Food and Drug Administration. Accessed on November 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer
