Phase 1 Trial Begins for HER2-targeted FT825 / ONO-8250 in Advanced Solid Tumors

Fate Therapeutics, a biopharmaceutical firm focused on developing cell-based therapies for cancer and autoimmune diseases, has announced the start of a Phase 1 clinical trial for its chimeric antigen receptor (CAR) T-cell product, FT825 / ONO-8250. This product is designed to target the human epidermal growth factor receptor 2 (HER2) and is engineered using induced pluripotent stem cells (iPSCs) to address challenges associated with solid tumors.

The collaboration with Ono Pharmaceutical Co., Ltd., which began in 2018, has led to the development of CD8 alpha-beta T cells from iPSCs and the integration of innovative synthetic controls into the CAR T-cell platform. These controls are aimed at enhancing cell trafficking, counteracting immune suppression in the tumor environment, and selectively targeting cancer cells. Scott Wolchko, Fate Therapeutics' CEO, highlighted the potential of FT825 / ONO-8250 to treat a variety of solid tumors, particularly those expressing HER2, including those with low HER2 expression levels.

The CAR T-cell product, FT825 / ONO-8250, includes seven novel synthetic controls, such as a CXCR2 receptor for improved cell movement, a chimeric TGFβ receptor to alter immunosuppressive signals in the tumor microenvironment, and a high-affinity CD16a receptor to facilitate antibody-dependent cellular cytotoxicity. Preclinical studies presented at a 2023 conference showed that the product's HER2-targeted antigen binding domain is distinct and more specific than trastuzumab, a standard treatment, without compromising potency.

The Phase 1 study will assess the safety, tolerability, pharmacokinetics, and anti-tumor activity of a single dose of FT825 / ONO-8250, both as a standalone therapy and in combination with monoclonal antibody therapy, in patients with advanced solid tumors who have previously received treatment. The trial will involve dose escalation and expansion to evaluate the product's overall response rate, duration of response, and disease control rate.

Under the agreement with Ono, Fate Therapeutics will co-develop and market FT825 / ONO-8250 in the U.S. and Europe, while Ono retains exclusive rights elsewhere. Fate is eligible for milestone payments and royalties on sales outside the U.S. and Europe. The companies are also working on another program targeting a different tumor-associated antigen.

Fate Therapeutics' iPSC platform allows for the production of a broad range of engineered cell products with novel synthetic controls. These cells are designed to offer multiple therapeutic benefits and can be stored for immediate use, combined with other treatments, and made available to a wide patient base. The platform is supported by an extensive intellectual property portfolio.

The company's iPSC-derived cell products, including natural killer (NK) and T-cell candidates, incorporate synthetic controls such as CARs to target tumor-associated antigens. These products are intended to work in conjunction with established cancer therapies, offering new options for patients with limited treatment choices. Fate Therapeutics is based in San Diego, California, and is working to advance its pipeline of first-in-class cell therapies.