Amgen's T-Cell Drug Approved by FDA for Hard-to-Treat Lung Cancer

The FDA has granted Amgen approval for its bispecific T-cell engager, tarlatamab, now marketed as Imdelltra, for the treatment of extensive-stage small lung cancer (ES-SCLC) in patients who have experienced disease progression following platinum-based chemotherapy. The approval was given under the FDA’s accelerated approval pathway, based on the observed response and duration of response. However, to maintain this approval, Amgen must confirm Imdelltra’s clinical benefits through a Phase III trial. Additionally, the FDA has included a boxed warning on Imdelltra's label concerning the risks of cytokine release syndrome and neurologic toxicity.

Jay Bradner, Chief Scientific Officer and Executive Vice President of R&D at Amgen, described the FDA’s approval as a "pivotal moment" for patients with ES-SCLC, highlighting Imdelltra as a "transformative option demonstrating long-lasting responses," particularly significant for those who have undergone prior treatments.

Imdelltra is administered intravenously and represents a first-in-class bispecific antibody. It targets both the DLL3 protein on tumor cells and the CD3 antigen on T cells. This dual-targeting mechanism activates the immune system to destroy DLL3-expressing cancer cells. DLL3 is present in a high percentage of SCLC cases—ranging from 85% to 96%—but is rarely found on healthy cells. Besides ES-SCLC, Amgen is also exploring tarlatamab for the treatment of neuroendocrine prostate cancer, which is currently in Phase I trials.

The accelerated approval of Imdelltra was supported by data from the Phase II DeLLphi-301 trial. This study administered Imdelltra at doses of either 10 mg or 100 mg every two weeks. In October 2023, Amgen published data from this trial in The New England Journal of Medicine, revealing an objective response rate of 40% for the 10-mg dose group and 32% for the 100-mg dose group. Among those showing an objective response to Imdelltra, 59% maintained this response for a median duration of at least six months. The median progression-free survival stood at 4.9 months for the 10-mg group, with an overall survival of 14.3 months.

Armed with these promising results, Amgen submitted its Biologics License Application to the FDA, which accepted the submission in December 2023 and granted it priority review. The FDA’s decision was originally expected by June 12, 2024.

The approval of Imdelltra provides Amgen a competitive edge in the oncology market, particularly against rivals such as Boehringer Ingelheim, which is currently evaluating its own SCLC bispecific T-cell engager, BI 764532, in a Phase II trial. Additionally, in November 2023, Novartis and Legend Biotech entered the competition with a potential $1-billion collaboration to develop a DLL3-targeting CAR-T therapy aimed at similar oncological indications.

This development represents a significant stride in the treatment landscape for extensive-stage small lung cancer, offering new hope for patients with limited options after initial therapies.