GFH375 KRAS-G12D Inhibitor Delivers 38% ORR — 52% in Pancreatic Cancer

GFH375 is an oral inhibitor that locks mutant KRAS G12D in both its GDP- and GTP-bound states. In a first-in-human Phase I/II study in China (NCT06500676), 32 heavily pre-treated patients with KRAS G12D-mutant solid tumors—11 PDAC, 11 NSCLC, 5 CRC, 5 others—received doses up to 900 mg QD or 300 mg BID. Among 22 response-evaluable patients, investigator-assessed ORR was 38% (42% in higher doses) with a 90% disease-control rate; 52% in PDAC patients. Grade 3/4 treatment-related AEs occurred in 25% (mostly GI and decreased neutrophils/WBCs), but no dose-limiting toxicities or deaths were seen.