FDA Grants Accelerated Approval to Tarlatamab-dlle for Extensive-Stage SCLC

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On May 16, the U.S. Food and Drug Administration (FDA) granted accelerated approval to tarlatamab-dlle (Imdelltra), a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3, for patients with extensive-stage small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.


Efficacy of the agent was evaluated in 99 patients with relapsed or refractory extensive-stage SCLC with disease progression following platinum-based chemotherapy enrolled in DeLLphi-301 ( identifier NCT05060016), an open-label, multicenter, multicohort study. Patients with symptomatic brain metastases, interstitial lung disease or noninfectious pneumonitis, and active immunodeficiency were excluded from enrollment. Patients received tarlatamab until disease progression or unacceptable toxicity.

The major efficacy outcome measures of the study were overall response rate per Response Evaluation Criteria in Solid Tumors version 1.1 and duration of response as assessed by blinded independent central review. The overall response rate was 40% (95% confidence interval [CI] = 31%–51%), and median duration of response was 9.7 months (range = 2.7 to 20.7+ months). Of the 69 patients with available data regarding platinum sensitivity status, the overall response rate was 52% (95% CI = 32%–71%) in 27 patients with platinum-resistant SCLC (defined as disease progression < 90 days after the last dose of platinum therapy) and 31% (95% CI = 18%–47%) in 42 patients with platinum-sensitive SCLC (defined as disease progression ≥ 90 days after the last dose of platinum therapy).

Safety and Adverse Events

The prescribing information for tarlatamab-dlle includes a Boxed Warning for serious or life-threatening cytokine-release syndrome and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome (ICANS). The most common adverse reactions (occurring in > 20% of patients who received the drug) were cytokine-release syndrome, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea. The most common grade 3 or 4 laboratory abnormalities (occurring in ≥ 5% of patients) were decreased lymphocytes, decreased sodium, increased uric acid, decreased total neutrophils, decreased hemoglobin, increased activated partial thromboplastin time, and decreased potassium.

The recommended tarlatamab dose is an initial dose of 1 mg administered as an intravenous infusion over 1 hour on day 1 of cycle 1, followed by 10 mg on day 8 of cycle 1, then day 15, then every 2 weeks thereafter until disease progression or unacceptable toxicity.

Expedited Programs

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for the concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Brazilian Health Regulatory Agency, Health Canada, Israel’s Ministry of Health, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency. The application reviews are ongoing at the other regulatory agencies involved with Project Orbis.

This review also 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 accelerated approval based on overall response rate and duration of response. Continued approval may be contingent upon verification of clinical benefit.

This application was granted Priority Review, Breakthrough Therapy designation, and Orphan Drug designation.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.