Amgen Halts Early-Stage Bispecific T-Cell Engager for Solid Tumors

Amgen announced on Monday that it has stopped the development of its investigational bispecific T-cell engager, AMG 794. The drug was being tested in a Phase I clinical trial for various solid tumors, including non-small cell lung cancer and epithelial ovarian cancer. According to an update on the clinicaltrials.gov website, Amgen decided to halt the AMG 794 program as a business decision but assured that the safety profile of the drug remains unchanged. The specific reasons for discontinuing the AMG 794 program have not been disclosed.

The termination of the AMG 794 program also means that Amgen will cease the ongoing Phase I study. This trial was focused on evaluating the safety and tolerability of the bispecific T-cell engager in several malignant solid tumor indications. AMG 794 was developed to target claudin-6, a tight junction protein vital for cell-to-cell connectivity, permeability, and adhesion. In cancerous conditions, claudin-6 is abnormally expressed, weakening tight junctions and causing cell layers to loosen, which contributes to cancer progression and metastasis. Claudin-6 is commonly found in malignant cells but is rarely present in healthy tissues.

AMG 794 remains listed in Amgen’s pipeline, highlighting its use of the company’s proprietary BiTE (bispecific T-cell engager) technology, which harnesses the body’s immune system to fight cancer. The molecule was designed to have an extended half-life, thereby prolonging its presence in patients' bodies. According to Amgen, these bispecific engagers include two targeting regions from two different antibodies. This structure enables the molecules to connect cytotoxic T cells with tumor cells, thereby promoting the immune system's cancer-fighting activity.

Amgen’s BiTE platform achieved a significant milestone in May 2024 when it secured accelerated approval for the bispecific molecule tarlatamab, marketed as Imdelltra, for extensive-stage small cell lung cancer. Imdelltra is intended for patients whose disease has progressed after platinum-based chemotherapy. Amgen is required to confirm the clinical benefits of Imdelltra in a subsequent trial to maintain its approval status.

Other pharmaceutical companies are also exploring bispecific T-cell engagers for cancer treatment. For instance, Roche has developed Columvi (glofitamab), which targets CD3 on T cells and CD20 on cancerous B cells. In June 2023, the FDA granted accelerated approval to Columvi for the treatment of relapsed or refractory diffuse large B-cell lymphoma.

Gilead Sciences is advancing the technology further with its investigational trispecific antibodies. In March 2024, Gilead partnered with Netherlands-based Merus to enhance this approach. Trispecific antibodies can bind to three targets simultaneously, potentially eliciting a more robust immune response against cancer.

Flavius Martin, executive vice president of research at Gilead, commented on these advancements, stating, “We have seen the successful application of bispecific antibodies as an immune-modulating modality used to treat cancer. 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.”

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