FDA Grants Accelerated Approval to Tarlatamab-dlle

Treatment for lung cancer with progression following platinum-based chemotherapy 

On May 16, 2024, the Food and Drug Administration (FDA) granted accelerated approval to Imdelltra (tarlatamab-dlle) manufactured by Amgen, Inc. for the treatment of extensive stage small cell lung cancer (ES-SCLC) in patients who have experienced disease progression following platinum-based chemotherapy. 

Efficacy and Safety 

The efficacy of tarlatamab-dlle was evaluated in the DeLLphi-301 study, an open-label, multicenter, multi-cohort trial involving 99 patients with relapsed or refractory ES-SCLC. Participants had progressed after receiving platinum-based chemotherapy and did not have symptomatic brain metastases, interstitial lung disease, non-infectious pneumonitis, or active immunodeficiency.  

Tarlatamab was administered until disease progression or unacceptable toxicity occurred. 

Key efficacy outcomes included: 

• Overall Response Rate (ORR): 40% (95% CI: 31-51) 
• Median Duration of Response (DOR): 9.7 months (range 2.7, 20.7+) 

Among 69 patients with known platinum sensitivity status, the ORR was: 

• 52% (95% CI: 32-71) in 27 patients with platinum-resistant SCLC (progression < 90 days after last platinum therapy) 
• 31% (95% CI: 18-47) in 42 patients with platinum-sensitive SCLC (progression ≥ 90 days after last platinum therapy) 

Safety and Warnings 

The prescribing information for tarlatamab-dlle includes a Boxed Warning for serious or life-threatening cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS).  

Common adverse reactions (>20%) included CRS, fatigue, fever, altered taste, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea.  

Common Grade 3 or 4 laboratory abnormalities (≥5%) included decreased lymphocytes, sodium, and potassium levels, increased uric acid, decreased neutrophils and hemoglobin, prolonged activated partial thromboplastin time, and increased potassium levels. 

Dosing Information 

The recommended dose of tarlatamab-dlle is an initial 1 mg intravenous infusion on Cycle 1 Day 1, followed by 10 mg on Cycle 1 Day 8 and Day 15, and then every two weeks until disease progression or unacceptable toxicity. 

Expedited Programs and Approval Process 

This accelerated approval was part of the FDA’s Project Orbis, allowing concurrent review by international regulatory partners including Brazil’s ANVISA, Health Canada, Israel’s Ministry of Health, and the UK’s MHRA.  

The review also utilized the Real-Time Oncology Review (RTOR) pilot program, streamlining data submission and facilitating a faster approval process, ultimately granting approval one month ahead of the goal date. 

Tarlatamab-dlle received priority review, breakthrough designation, and orphan drug designation. Continued approval may depend on verification of clinical benefit in further studies. 

Reporting Adverse Events 

Healthcare professionals are urged to report serious adverse events associated with tarlatamab-dlle to the FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088. 

This significant approval marks an important advancement in the treatment options available for patients with extensive stage small cell lung cancer, providing hope for those who have not responded to traditional therapies. Read the FDA approval announcement.