FMC-242 + divarasib

FMC-242 + divarasib is an investigational, preclinical combination of two targeted oncology agents: FMC-242, an orally bioavailable, covalent allosteric small-molecule inhibitor of the PI3Kα–RAS interaction, and divarasib (GDC-6036), an oral, next-generation KRAS G12C inhibitor. FMC-242 selectively binds to cysteine 242 in the RAS-binding domain of PI3Kα, disrupting the PI3Kα–RAS interaction and downstream AKT signaling without affecting normal PI3Kα catalytic functions or glucose homeostasis. Divarasib covalently binds to and locks KRAS G12C in its inactive GDP-bound state, blocking downstream oncogenic signaling. Developed by Frontier Medicines (FMC-242) and Genentech/Roche (divarasib), this combination has demonstrated enhanced anti-tumor activity and tumor regressions in preclinical KRAS G12C-mutant and HER2-amplified/RTK-driven xenograft models, including those resistant to single-agent KRAS inhibitors.

Other names

FMC-242 and divarasibFMC242 and divarasibFMC 242 and divarasibdivarasib + FMC-242divarasib and FMC-242