Amgen’s Tarlatamab Gets FDA Priority Review for Small Cell Lung Cancer

Amgen recently reported that the US Food and Drug Administration (FDA) has given priority review status to its drug candidate, tarlatamab, intended for the treatment of small-cell lung cancer (SCLC). If approved, tarlatamab could bring about significant improvements compared to existing options or potentially offer a treatment alternative in cases where no adequate therapy currently exists.

“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,” said David M. Reese, executive vice president of Research and Development at Amgen, in the company’s press release.

Tarlatamab is an investigational drug currently undergoing clinical trials to assess its efficacy in patients with two distinct types of neuroendocrine cancer: SCLC and neuroendocrine prostate cancer (NEPC). Classified as a bispecific T-cell engager (BiTE molecule), tarlatamab consists of two essential parts: one binds to T-cells, vital in immune response, and the other targets cancer cells.

Tarlatamab differs from conventional chemotherapy as it’s an immunotherapy designed to help immune cells detect, attach to and fight cancer cells. It targets delta-like ligand 3 (DLL3), a protein usually found inside normal cells but abnormally present on the surface of SCLC cells. As a bispecific T-cell engager immunotherapy, tarlatamab directs the patient’s T cells to attack cancer cells exhibiting DLL3.

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Clinical Evidence of Tarlatamab

The FDA’s decision to grant tarlatamab priority review stems from the Phase II DeLLphi-301 clinical trial results, published in The New England Journal of Medicine. This study evaluated the effectiveness and safety of tarlatamab, administered intravenously in 10 mg or 100 mg doses biweekly, in patients with previously treated SCLC. Results demonstrated significant antitumor activity, durable objective responses and encouraging survival rates in these patients.

Following the Phase II data analysis, the 10-mg dose was chosen for subsequent tarlatamab trials due to its more favorable benefit-to-risk profile compared to the 100-mg dose. The 10-mg dose demonstrated an objective response in 40 percent of patients, with a median overall survival of 14.3 months (the median duration of response was not evaluable). The observed objective response rate of 40 percent significantly surpassed the historical control benchmark of 15 percent for the primary endpoint.

The clinical study further underscored the favorable tolerability profile of tarlatamab. Among the most prevalent adverse events, cytokine-release syndrome occurred in 51 percent of patients in the 10-mg group and 61 percent in the 100-mg group. Additionally, decreased appetite was reported in 29 percent and 44 percent of patients, respectively, while pyrexia occurred in 35 percent of the 10-mg group and 33 percent of the 100-mg group.

In light of the priority review designation, the Prescription Drug User Fee Act (PDUFA) date for tarlatamab is scheduled for June 12, 2024. Concurrently, Amgen has outlined plans to commence an additional Phase III study for tarlatamab, focusing on its application in the first-line treatment of SCLC.

New Drugs Approved for Small-Cell Lung Cancer

Several drugs have received FDA approval for treating SCLC. In 2020, the FDA approved AstraZeneca’s Imfinzi (durvalumab) for use in combination with etoposide and either carboplatin or cisplatin as a first-line treatment for SCLC.

Similarly, in the same year, Pharma Mar’s Zepzelca (lurbinectedin) also received FDA approval for the treatment of SCLC.

Additionally, in 2019, the FDA granted approval for Merck’s Keytruda (pembrolizumab) for the same purpose.