FDA Approves Bispecific Antibody for Small Cell Lung Cancer

The FDA has granted accelerated approval for Amgen’s Imdelltra (tarlatamab-dlle) to treat adult patients with extensive-stage small cell lung cancer (ES-SCLC). It is indicated for patients with disease progression on or after platinum-based chemotherapy.

About 10% to 15% of all lung cancers are small cell, according to the American Cancer Society. Small cell lung cancer is an aggressive solid tumor with a median survival of about 12 months following initial therapy and a 3% five-year relative survival rate.

David P. Carbone, M.D., Ph.D.

“Lung cancer is a complex and devastating disease, and less than 3% of patients with ES-SCLC live longer than five years,” David P. Carbone, M.D., Ph.D., professor of internal medicine and director of the James Thoracic Oncology Center at the Ohio State University Medical Center, said in a news release.

Imdelltra is a first-in-class delta-like ligand 3 (DLL3) targeting Bispecific T-cell Engager (BiTE) therapy and the first bispecific antibody for extensive-stage small cell lung cancer. Imdelltra targets CD3 on T cells and DLL3 on small cell lung cancer cells. About 85% to 96% of patients have expression of DLL3 on the cell surface of small cell lung cancer cells, with minimal expression in normal cells.

Imdelltra will have a list price of $31,500 for the first cycle and $30,000 for the second cycle, according an Amgen spokesperson. Amgen will host a webcast call on Monday, May 20, 2024 at 1:00 p.m. PT (4:00 p.m. ET).

The accelerated approval was based on the response rate and duration of response seen in the phase 2 DeLLphi-301 clinical trial, which studied 220 patients with advanced small cell lung cancer. Imdelltra demonstrated an objective response rate of 40% and a median duration of response 9.7 months. The median overall survival was 14.3 months.

The most common adverse reactions reported among patients were cytokine release syndrome, fatigue, fever, metallic taste in the mouth, decreased appetite, musculoskeletal pain, constipation, anemia and nausea. Additionally, 7% of patients discontinued treatment because of adverse events.

The Imdelltra label includes a boxed warning for cytokine release syndrome and neurologic toxicity, in addition to warnings and precautions for cytopenias, infections, hepatotoxicity, hypersensitivity, and embryo-fetal toxicity.

Results from the study were recently presented during the 2023 European Society for Medical Oncology (ESMO) Congress and published in the New England Journal of Medicine.

Amgen is conducting additional trials of Imdelltra in small cell lung cancer: a phase 1b study evaluating tarlatamab in combination with an anti-PD-1 therapy in second-line treatment; a phase 1b study investigating tarlatamab in combination with standard of care therapies in first-line treatment; and a phase 3 trial comparing tarlatamab monotherapy with standard of care chemotherapy in second-line treatment; and the recently-initiated phase 3 trial of tarlatamab following chemoradiotherapy in earlier settings.

Amgen is also investigating tarlatamab in a phase 1b study of tarlatamab in de novo or treatment-emergent neuroendocrine prostate cancer.