On November 19, 2025, the Food and Drug Administration granted traditional approval to tarlatamab-dlle (Imdelltra, Amgen Inc.) for adults with extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. Tarlatamab-dlle received accelerated approval for this indication in 2024.
Full prescribing information for Imdelltra will be posted on Drugs@FDA.
Efficacy was evaluated in DeLLphi-304 (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-(L)1 antibody. In DeLLphi-304, 509 patients were randomized (1:1) to receive either tarlatamab-dlle or investigator’s choice of standard of care (SOC) chemotherapy (topotecan, lurbinectedin, or amrubicin) until disease progression or unacceptable toxicity.
The major efficacy outcome measure was overall survival (OS). Key secondary efficacy outcome measures included progression-free survival (PFS) based on investigator assessment per RECIST v 1.1 and select patient-reported outcomes. Median OS was 13.6 months (95% CI: 11.1, not evaluable) in the tarlatamab-dlle arm and 8.3 months (95% CI: 7.0, 10.2) in the SOC arm (hazard ratio [HR] 0.60 [95% CI: 0.47, 0.77]; p-value <0.001). Median PFS was 4.2 months (95% CI: 3.0, 4.4) and 3.2 months (95% CI: 2.9, 4.2) in the respective arms (HR 0.72 [95% CI: 0.59, 0.88]; p-value <0.001). The trial also demonstrated a statistically significant improvement in dyspnea at week 18 for patients randomized to tarlatamab-dlle compared to SOC.
The prescribing information for tarlatamab-dlle includes a Boxed Warning for life-threatening or fatal cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), as well as warnings and precautions for cytopenias, infections, hepatotoxicity, hypersensitivity, and embryo-fetal toxicity.
The recommended tarlatamab-dlle dose is 1 mg on Cycle 1, Day 1 followed by 10 mg on Days 8, 15, and every two weeks thereafter until disease progression or unacceptable toxicity.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada (HC), and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA). The application reviews are ongoing at the other regulatory agencies.
This review used the Real-Time Oncology Review (RTOR) 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-dlle received breakthrough designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
Follow the Oncology Center of Excellence on X: @FDAOncology.
