On November 19, the U.S. Food and Drug Administration (FDA) granted traditional approval to tarlatamab-dlle (Imdelltra), a DLL3-targeting bispecific T-cell engager, for adults with extensive-stage small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Tarlatamab received accelerated approval for this indication in 2024.
DeLLphi-304
Efficacy was evaluated in DeLLphi-304 (ClinicalTrials.gov identifier NCT05740566), a multicenter, randomized, open-label trial in patients with SCLC with disease progression following treatment with platinum-based chemotherapy with or without an anti–PD-1/L1 antibody. In DeLLphi-304, 509 patients were randomly assigned 1:1 to receive either tarlatamab or investigator's choice of standard of care chemotherapy (topotecan, lurbinectedin, or amrubicin) until disease progression or unacceptable toxicity.
The major efficacy outcome measure was overall survival; key secondary efficacy outcome measures included progression-free survival based on investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 and select patient-reported outcomes. Median overall survival was 13.6 months (95% confidence interval [CI] = 11.1 months to not evaluable) in the tarlatamab arm and 8.3 months (95% CI = 7.0–10.2 months) in the standard-of-care arm (hazard ratio [HR] = 0.60, 95% CI = 0.47, 0.77, P < .001). Median progression-free survival was 4.2 months (95% CI = 3.0–4.4 months) and 3.2 months (95% CI = 2.9–4.2 months) in the respective arms (HR = 0.72, 95% CI = 0.59–0.88, P < .001). The trial also demonstrated a statistically significant improvement in dyspnea at week 18 for patients receiving tarlatamab compared to standard of care.
The prescribing information for tarlatamab includes a Boxed Warning for life-threatening or fatal cytokine release syndrome and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome, as well as warnings and precautions for cytopenias, infections, hepatotoxicity, hypersensitivity, and embryo-fetal toxicity.
The recommended tarlatamab dose 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.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence which provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and the United Kingdom's Medicines and Healthcare products Regulatory Agency. The application reviews are ongoing at the other regulatory agencies.
This review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA's assessment. The FDA approved this application 1 month ahead of the FDA goal date.
This application was granted Priority Review. Tarlatamab received Breakthrough Therapy designation.
