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FDA grants full approval to tarlatamab-dlle for relapsed extensive-stage small cell lung cancer

On November 19, 2025, the U.S. Food and Drug Administration (FDA) granted traditional approval to tarlatamab dlle for adults with extensive stage small cell lung cancer (ES-SCLC) after progression on platinum based chemotherapy. 1 ES-SCLC remains an aggressive neuroendocrine lung cancer subtype characterized by rapid growth, early metastasis, and high relapse rates despite initial responsiveness to first line therapy. Treatment options after progression have historically produced limited survival benefits and substantial toxicity, underscoring the need for more effective second line approaches. 2, 3

The decision is supported by data from the global Phase III randomized open label DeLLphi-304 trial (NCT05740566), initiated in 2023, which enrolled 509 patients randomized 1:1 to receive tarlatamab or investigator choice of standard chemotherapy. The primary endpoint overall survival (OS) was met. Median OS for tarlatamab reached 13.6 months (95% CI 11.1 to not evaluable) compared with 8.3 months (95% CI 7.0 to 10.2) for chemotherapy (hazard ratio [HR] 0.60 [95% CI 0.47 to 0.77]; P < 0.001). 1

Among secondary outcomes, investigator assessed progression-free survival (PFS) was 4.2 months (95% CI 3.0 to 4.4) for tarlatamab and 3.2 months (95% CI 2.9 to 4.2) for chemotherapy (HR 0.72; 95% CI 0.59 to 0.88; P < 0.001). A statistically significant improvement in patient reported dyspnea at week 18 was also observed in favor of tarlatamab. 1 Safety data demonstrated a more favorable profile for tarlatamab than for chemotherapy. Grade ≥3 adverse events occurred in 54% of patients receiving tarlatamab compared with 80% receiving standard chemotherapy. 1

Martin Schuler, MD, University Hospital Essen, commented on the significance of the findings: “The DeLLphi-304 is the first Phase III study to demonstrate superiority of tarlatamab over three choices of standard chemotherapy for second-line treatment of patients with small cell lung cancer. The study demonstrated a clear survival benefit and also a benefit of progression-free survival with a risk reduction for deaths of 40%”

With full approval now secured, tarlatamab dlle becomes the first therapy in this setting to demonstrate a meaningful and statistically significant survival advantage over established chemotherapy, marking a pivotal advancement in the management of relapsed ES-SCLC.

References:

  1. U.S. Food and Drug Administration. FDA grants traditional approval to tarlatamab dlle for extensive stage small cell lung cancer. Published 19 Nov 2025. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer
  2. Meriggi F. Second line treatment options for small cell lung cancer A light at the end of the tunnel. Curr Oncol. 2024 Jan 5;16(2):255. doi: 10.3390/cancers16020255. 
  3. Papavasileiou S. New therapies in small cell lung cancer A narrative review. Pneumon. 2024;37(1):13. doi:10.18332/pne/183168.

Written by Henry Shippey

Edited by Calum Lang