The first patient has been dosed in a first-in-human Phase I trial of GB-5267, an autologous IL-18-armored CAR T-cell therapy targeting MUC16, developed by Generate Biomedicines (Nasdaq: GENB) in collaboration with Roswell Park Comprehensive Cancer Center in Buffalo, New York, for patients with platinum-resistant or recurrent ovarian cancer. The trial (NCT07489287) is evaluating safety and tolerability in an estimated 18 patients, with GB-5267 administered both intravenously and intraperitoneally. The study does not require lymphodepleting chemotherapy before infusion, a design intended to avoid toxicities associated with lymphodepletion.
GB-5267 targets MUC16, also known as CA125, a transmembrane mucin overexpressed in more than 80% of ovarian tumors and implicated in tumor progression, metastasis, and immune evasion. The CAR T cells are armored to secrete IL-18 locally, with the aim of counteracting the immunosuppressive tumor microenvironment and improving T-cell proliferation and persistence. Preclinical studies reported enhanced expansion and persistence of IL-18-secreting MUC16-directed CAR T cells in ovarian tumor models. Generate said the therapy was designed using AI-based methods that optimized CAR architectures according to T-cell behavior, including potency, proliferation, and persistence, rather than binding affinity alone.
Treatment options after platinum failure include single-agent chemotherapy, bevacizumab-containing regimens, and mirvetuximab soravtansine-gynx (Elahere), a folate receptor alpha-targeting antibody-drug conjugate that received traditional US FDA approval in 2024.