FDA Approves Tarlatamab-dlle for Advanced Lung Cancer Treatment

On November 19, 2025, the FDA granted traditional approval to tarlatamab-dlle, marketed as Imdelltra, for adults with extensive stage small cell lung cancer, or ES-SCLC, who have experienced disease progression following platinum-based chemotherapy.

This approval follows an earlier accelerated approval in 2024. Efficacy was demonstrated in the DeLLphi-304 trial, a multicenter, randomized, open-label study involving five hundred nine patients with SCLC who had disease progression after platinum-based chemotherapy, either alone or in combination with an anti-PD-(L)1 antibody.

The trial randomized patients in a one-to-one ratio to receive either tarlatamab-dlle or standard of care chemotherapy options, which included topotecan, lurbinectedin, or amrubicin, until disease progression or unacceptable toxicity occurred.

The primary efficacy measure was overall survival, with key secondary measures including progression-free survival and select patient-reported outcomes. The results showed a median overall survival of 13.6 months in the tarlatamab-dlle group compared to 8.3 months in the standard of care group, indicating a significant improvement with a hazard ratio of 0.60, with a p-value of less than 0.001.

Progression-free survival also showed improvement, with 4.2 months in the tarlatamab-dlle arm versus 3.2 months in the standard of care arm, and a hazard ratio of 0.72, also with a p-value of less than 0.001.

Additionally, patients receiving tarlatamab-dlle experienced a statistically significant reduction in dyspnea at week 18 compared to those receiving standard therapy. Notably, the prescribing information for tarlatamab-dlle includes a Boxed Warning for potentially life-threatening or fatal cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome.

Other warnings address risks of cytopenias, infections, hepatotoxicity, hypersensitivity, and embryo-fetal toxicity. The recommended dosage begins at 1 milligram on Cycle one, Day one, followed by 10 milligrams on Days eight, fifteen, and biweekly thereafter until disease progression or unacceptable toxicity occurs.

This approval was part of Project Orbis, which facilitates concurrent international submissions and reviews for oncology drugs, and the FDA collaborated with agencies from Australia, Canada, and the United Kingdom in this process.

The application was granted priority review and approved one month ahead of schedule, reflecting the urgency of addressing the needs of patients with advanced lung cancer. Healthcare professionals are encouraged to report any serious adverse events associated with tarlatamab-dlle to the FDA's MedWatch Reporting System.