Tarlatamab Application for SCLC Granted Priority Review by FDA

The FDA announced on December 13 that it had granted priority review to an application for the approval of tarlatamab, which is an investigational delta-like ligand 3–targeting bispecific T-cell engager therapy that would treat adult patients with advanced small cell lung cancer (SCLC) who had disease progression either during or after treatment with platinum-based chemotherapy. The current Prescription Drug User Fee Action date for the decision is June 12, 2024.

"The FDA's Priority Review designation for this application underscores the urgency to provide new treatment options for patients with advanced SCLC who have progressed following treatment with platinum-based chemotherapy," David M. Reese, MD, executive vice president of Research and Development at Amgen, said in a press release.¹

Lungs | Image credit: yodiyim - stock.adobe.com

SCLC is a solid tumor with a median survival of about 12 months after therapy and a 5-year relative survival rate of 7%. SCLC makes up about 15% of all lung cancer cases worldwide. Platinum-based first-line chemotherapy has a high response rate initially, but patients relapse quickly after treatment, which necessitates other treatment options. Tarlatamab may be an answer to this need. The targeted therapy can bring T cells closer to SCLC cells within a patient with SCLC.

The phase 2 results of DeLLphi-301 are the basis of the biologics license application. The study assessed patients with advanced SCLC who had disease progression after or during platinum-based chemotherapy. The study results were published in the New England Journal of Medicine.²

The study included 220 patients who received tarlatamab, with all patients previously using a median of 2 lines of treatment. The group receiving 10 mg had a median follow up of 10.6 months and the group receiving 100 mg had 10.3 months of follow up. There was objective response of 40% (97.5% CI, 29%-52%) for the 10 mg group and 32% (97.5% CI, 21%-44%) for the 100 mg group.

The duration of response was at least 6 months in 59% of those who had an objective response. A total of 55% of patients in the 10 mg group and 57% in the 100 mg group had ongoing objective response at the data cut off. Median progression-free survival was 4.9 months (95% CI, 2.9-6.7) in the 10 mg group and 3.9 months (95% CI, 2.6-4.4) in the 100 mg group. Decreased appetite, cytokine release syndrome, and pyrexia were the most common adverse events. The study concluded that patients with SCLC who received tarlatamab in a 10 mg dose every 2 weeks had antitumor activity, durable objective responses, and promising survival outcomes.

The priority review application comes after tarlatamab was granted a Breakthrough Therapy Designation in October, which is currently being reviewed under the Real Time Oncology Review and the Project Orbis framework.

Other studies are currently being conducted to test the effectiveness of tarlatamab in this population. DeLLphi-302 is a phase 1b study that is evaluating the effectiveness of combining tarlatamab with an anti–PD-1 therapy in second-line SCLC. Use of tarlatamab in first-line SCLC in combination with standard of care therapies is being studied in DeLLphi-303, a phase 1b study. A phase 3 trial comparing tarlatamab monotherapy with standard of care chemotherapy in second-line treatment of SCLC is being conducted in DeLLphi-304. And lastly, DeLLphi-306 is a randomized phase 3 trial using tarlatamab after chemoradiotherapy.

Reference

1. FDA grants priority review to Amgen’s tarlatamab application for advanced small cell lung cancer. News Release. Amgen. December 13, 2023. Accessed December 14, 2023. https://www.amgen.com/newsroom/press-releases/2023/12/fda-grants-priority-review-to-amgens-tarlatamab-application-for-advanced-small-cell-lung-cancer
2. Ahn MJ, Cho BC, Felip E, et al Tarlatamab for patients with previously treated small-cell lung cancer. N Engl J Med. 2023;389:2063-2075. doi:10.1056/NEJMoa2307980