Phase 2 daraxonrasib pan-RAS(ON) tri-complex inhibitor targets KRAS-mutant biliary tract cancer.

This multi-institutional Phase 2, open-label, single-arm study evaluates daraxonrasib monotherapy in patients with unresectable or advanced/metastatic biliary tract cancers (including cholangiocarcinoma, gallbladder cancer, and ampullary cancers) whose tumors harbor a KRAS mutation and who progressed on—or were intolerant of—one prior first-line systemic regimen. Daraxonrasib (RMC-6236) from Revolution Medicines is an oral, multi-selective RAS(ON) inhibitor that works by forming a tri-complex with cyclophilin A and active RAS to suppress signaling across multiple KRAS variants (rather than only KRAS G12C). The sponsor is Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, positioning this as a focused “KRAS-mutant BTC” signal-finding study where KRAS alteration rates vary by subsite (higher in ampullary than many other BTC subsets). Today’s care after first-line gemcitabine/cisplatin plus an immune checkpoint inhibitor (commonly durvalumab) is typically second-line chemotherapy such as FOLFOX or clinical trials, so this tests whether broad RAS pathway blockade can deliver a targeted option in a genomically defined post–first-line population.