GENFLEET-B (02595) announced the initiation of its registrational Phase III trial (GFH375X1301) for GFH375, an oral KRAS G12D (ON/OFF) inhibitor, in patients with previously treated KRAS G12D-mutated metastatic pancreatic cancer at Peking University Cancer Hospital. GFH375 is currently among the global frontrunners in oral KRAS G12D inhibitor development, with multiple monotherapy and combination trials underway in China (led by GENFLEET) and overseas (led by partner Verastem Oncology). These include GFH375 (known as VS-7375 outside China) combined with chemotherapy (nab-paclitaxel and gemcitabine, AG) as first-line treatment for advanced pancreatic ductal adenocarcinoma (PDAC). The drug has also received FDA Fast Track designation for treating locally advanced/metastatic KRAS G12D-mutated PDAC across treatment lines.
The multicenter, open-label, randomized controlled Phase III trial (GFH375X1301) will enroll approximately 320 patients across 40 sites who have received at least one prior systemic therapy. Industry data projects global pancreatic cancer cases to exceed 770,000 by 2037, with the disease's high malignancy and poor prognosis yielding a 5-year survival rate below 10%. Current treatments remain chemotherapy-dominated, showing 10-20% objective response rates (ORR) in second-/third-line settings, with no standard options beyond third-line.
Scientific literature indicates KRAS G12D mutations occur in nearly 40% of pancreatic cancer patients, yet no targeted therapies are approved worldwide. This mutation serves as an independent prognostic marker for poor response and overall survival in advanced PDAC, while also promoting immunosuppressive tumor microenvironments and resistance to checkpoint inhibitors.
Dr. Wang Yu, GENFLEET’s Chief Medical Officer, stated: "This marks the world’s first registrational study of an oral RAS inhibitor for pancreatic cancer, demonstrating our clinical execution capabilities and integrated drug development expertise in RAS therapeutics. GFH375 entered trials last year and has already generated promising Phase I/II monotherapy data, advancing into multiple combination studies. We anticipate positive outcomes from this registrational trial to benefit patients soon, alongside future breakthroughs from our RAS pipeline and synergistic approaches with cachexia bispecific therapies for pancreatic cancer."