FDA approves Amgen T-cell engager for small cell lung cancer

The US Food and Drug Administration (FDA) has approved Amgen’s Imdelltra™ (tarlatamab-dlle), a bispecific T-cell engager, for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).

The drug received accelerated regulatory approval based on the “encouraging response rate and duration of response (DoR) observed in clinical studies,” Amgen said.

FDA’s approval of Imdelltra was based on results from the Phase II DeLLphi-301 clinical trial. This study evaluated the T-cell engager in patients with SCLC who had failed two or more prior lines of treatment. Patients received doses of 10mg every two weeks.

“In the DeLLphi-301 trial, the median overall survival was 14.3 months, with 40 percent of patients responding to treatment with tarlatamab,” commented David P. Carbone, Professor of internal medicine and director of the James Thoracic Oncology Center at the Ohio State University Medical Center.

“These responses were remarkably durable, representing a major advancement in the SCLC treatment paradigm,” he added.

How the T-cell engager therapy works

Imdelltra is the first and only DLL3-targeting bispecific T-cell engager therapy that activates the patient’s own T cells to attack DLL3-expressing tumour cells.

The DLL3 protein is expressed on the surface of SCLC cells in some 85 to 96 percent of patients with the disease, but is minimally expressed on healthy cells, making it an exciting target.

The T-cell engager works by binding to both DLL3 on tumour cells and CD3 on T cells, activating T cells to kill DLL3-expressing SCLC cells. This results in the formation of a cytolytic synapse with lysis of the cancer cell.

“This approval further demonstrates our commitment to addressing aggressive cancers through our second FDA-approved Bispecific T-cell Engager (BiTE^®) molecule, “ said Jay Bradner, MD, executive vice president, Research and Development, and chief scientific officer at Amgen.

Amgen is also developing and investigating tarlatamab for the treatment of neuroendocrine prostate cancer.

Continued FDA approval of Imdelltra for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).