Amgen has quietly discontinued the development of its Phase I bispecific T-cell engager AMG 794, which the company had been studying for several malignant solid tumors.
Amgen on Monday terminated the development of its investigational bispecific T-cell engager AMG 794, which it had been studying in a Phase I trial for several solid tumors including non-small cell lung cancer and epithelial ovarian cancer.
In an update to the clinicaltrials.gov website, the company noted that it “made the business decision to discontinue development of AMG 794” while maintaining that “the safety profile of AMG 794 remains unchanged.” It is not clear what exactly led to the termination of the AMG 794 program.
In line with the discontinuation of AMG 794, Amgen will also stop the Phase I study which was assessing the safety and tolerability of the bispecific T cell engager in several malignant solid tumor indications.
AMG 794 was designed to target claudin-6, a tight junction protein crucial to the connectivity, permeability and adhesion between cells. In cancer, claudin-6 is abnormally expressed compromising the tight junction and loosening cell layers—a key hallmark of cancer progression and metastasis. Claudin-6 is typically highly expressed in malignant cells but is rare in healthy tissues.
The bispecific T-cell engager is still listed on Amgen’s pipeline, which indicates that the molecule uses its proprietary BiTE technology that leverages the body’s immune functions to treat cancer. AMG 794 was also designed to have an extended half-life, prolonging its presence in patients’ bodies.
According to the pharma’s website, these bispecific engagers consist of two targeting regions of two antibodies. This structure allows these molecules to create a bridge cytotoxic T cells and tumor cells, facilitating the immune system’s anti-cancer activity.
In May 2024, Amgen’s BiTE platform resulted in an accelerated approval for the bispecific molecule tarlatamab, which is now being marketed under the brand name Imdelltra for extensive-stage small cell lung cancer. Imdelltra can be used in patients with disease progression on or after platinum chemotherapy. Amgen will need to validate Imdelltra’s clinical benefit in a confirmatory trial to maintain its approval.
Several other companies are also leveraging bispecific T-cell engagers for cancer. Roche owns Columvi (glofitamab) which targets CD3 on T cells and CD20 on cancerous B cells. In June 2023, the FDA granted Columvi accelerated approval for relapsed or refractory diffuse large B-cell lymphoma.
Gilead Sciences is pushing the technology even further with its investigational trispecific antibodies. In March 2024, the company partnered with Netherlands-based Merus to advance this approach, which can bind three targets simultaneously and potentially lead to a more robust immune response against cancer.
“We have seen the successful application of bispecific antibodies as an immune-modulating modality used to treat cancer,” Flavius Martin, executive vice president of research at Gilead, said in a statement at the time. “We are now looking ahead to the development of additional multispecific antibodies capable of driving robust anti-tumor immune responses with an improved efficacy and safety profile.”
