Zoldonrasib, also known as RMC-9805, is an investigational drug that selectively targets the G12D mutation in KRAS dependent cancers. Zoldonrasib functions as molecular glue that forms a non-covalent ligand-mediated protein-protein interaction between cyclophilin A and GTP-bound RAS. Subsequent covalent modification of the mutant Asp12 residue affords selectivity over wild-type RAS.
As of 2025, zoldonrasib is in a phase 1/1b clinical trial for the treatment of KRAS G12D-mutant solid tumors. Preliminary data indicated that KRAS G12DâÂÂmutant PDAC patients dosed at 1200 mg daily or 600 mg twice daily achieved a 30% objective response rate (n = 12) and 80% disease control rate (n = 32).