In a global phase 3 trial of 509 patients with small cell lung cancer that had come back, people given tarlatamab lived longer than those on standard chemotherapy. Median overall survival was 13.6 months against 8.3 months, a 40% reduction in the risk of death.
Those results led the US Food and Drug Administration to give full approval to tarlatamab (brand name Imdelltra) on November 19, 2025. The drug is cleared for adults with extensive-stage small cell lung cancer (ES-SCLC) whose disease progressed on or after platinum-based chemotherapy.
From accelerated to full approval
The FDA first granted accelerated approval in May 2024, based on the phase 2 DeLLphi-301 trial. Targeted Oncology called it the first bispecific T-cell engager (BiTE) approved for a major solid tumor. In that trial the objective response rate was 40%, with a median duration of response of 9.7 months. The agency had given the application priority review in December 2023 and breakthrough therapy designation in October 2023.
Tarlatamab connects a patient’s immune cells to cancer cells so the immune cells can attack the tumor directly.
What DeLLphi-304 found
The confirmatory study, DeLLphi-304, was led by Charles M. Rudin of Memorial Sloan Kettering Cancer Center. Patients were randomly assigned to tarlatamab or to chemotherapy with lurbinectedin, topotecan or amrubicin. The median age was 64 years in the tarlatamab arm and 66 in the chemotherapy arm.
Tarlatamab also cut the risk of disease progression or death by 28%. Median progression-free survival was 4.2 months, against 3.2 months with chemotherapy. The objective response rate was 35% versus 20%. Patients whose cancer had reached the brain also benefited, even though that is usually a sign of aggressive disease.
Fewer people had to change course because of side effects. Dose interruption or reduction from treatment-related adverse events hit 19% of patients on tarlatamab and 55% of those on chemotherapy. Grade 3 treatment-related events occurred in 27% and 62% respectively. Cytokine release syndrome, dysgeusia, pyrexia and decreased appetite were more common with tarlatamab, while anemia, neutropenia and thrombocytopenia were more common with chemotherapy.
Cytokine release syndrome appeared in 60% of the patients monitored for 48 hours during the first two cycles. Most cases were grade 1 (45%) or grade 2 (13%), and 1% were grade 3.
Patients on tarlatamab reported fewer symptoms such as cough and trouble breathing. At week 18, 16.1% of the tarlatamab group reported cough improvement versus 9.0% of the control group.
Small cell lung cancer is highly aggressive, with a shorter doubling time and earlier metastases than non-small cell types. The Lung Cancer Foundation of America called the approval a new, more effective and gentler option for many people whose disease has relapsed.
Sources
- FDA Fully Approves New Lung Cancer Drug Tarlatamab | LCFA
- FDA Grants Full Approval to Tarlatamab for Extensive-Stage Small Cell Lung Cancer | OncLive
- FDA Grants Approval to Tarlatamab in Small Cell Lung Cancer | Targeted Onc – Immunotherapy, Biomarkers, and Cancer Pathways
- Small-cell carcinoma
