GFH276 + cetuximab

GFH276 + cetuximab is an investigational combination regimen consisting of GFH276, an orally administered small-molecule pan-RAS (ON) inhibitor, and cetuximab (Erbitux), an approved intravenous anti-EGFR monoclonal antibody. Developed by GenFleet Therapeutics, GFH276 acts as a molecular glue that recruits intracellular cyclophilin A (CypA) to form a tri-complex, thereby inhibiting active, GTP-bound wild-type and mutant RAS proteins (including KRAS, NRAS, and HRAS isoforms). Cetuximab binds to and antagonizes the epidermal growth factor receptor (EGFR), blocking upstream signaling. By combining these two agents, the regimen aims to achieve synergistic anti-tumor activity and overcome adaptive resistance mechanisms in RAS-mutant cancers. The combination is currently being evaluated in Phase Ib/II clinical trials for patients with advanced solid tumors, pancreatic ductal adenocarcinoma (PDAC), and metastatic colorectal cancer (mCRC) harboring RAS mutations.

Other names

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