GenFleet Therapeutics, a commercial-stage biotechnology company developing cutting-edge therapies in oncology and immunology, announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to GFH375/VS-7375, an oral KRAS G12D (ON/OFF) inhibitor, for treatment of patients with KRAS G12D-mutated locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). Following the IND approval for a phase I/II study in China in June 2024, GFH375/VS-7375 has advanced into phase II in China while a phase I/IIa trial was initiated in the U.S. by GenFleet's partner Verastem Oncology.
Fast Track is a process designed by the FDA to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Programs with FTD are eligible for more frequent interactions with FDA to discuss the candidate’s development plan, as well as a rolling review of NDA or BLA to facilitate Accelerated Approval and Priority Review if relevant criteria are met.
According to the rapid oral presentation at 2025 ASCO annual meeting, preliminary phase I data demonstrated good oral bioavailability and anti-tumor activities of GFH375, with encouraging efficacy in treating multiple tumor types including PDAC and non-small cell lung cancer (NSCLC): as of the data cutoff date, the overall ORR was 38% and DCR was 90% among the 52 patients across all dose levels and indications who received at least one post-treatment tumor assessment; 23 efficacy-evaluable patients with PDAC and 12 efficacy-evaluable patients with NSCLC, who received daily dosages of 400 or 600 mg, achieved an ORR of 52% and DCR of 100%, and an ORR of 42% and a DCR of 83%, respectively.
About GFH375/VS-7375
GFH375 is an orally active, potent, highly selective small-molecule KRAS G12D (ON/OFF) inhibitor designed to target the GTP/GDP exchange, thereby disrupting the activation of downstream pathways and effectively inhibiting tumor cell proliferation. Preclinical studies demonstrated dose-dependent inhibition in models bearing KRAS G12D mutation; GFH375 also demonstrated low off-target risk in kinase selectivity and safety target assays. GenFleet entered into a discovery and development collaboration with Verastem Oncology (Nasdaq: VSTM) to advance three novel oncology discovery programs related to RAS/MAPK pathway-driven cancers. The collaboration provides Verastem with an exclusive option to obtain a license for each of the three compounds in the collaboration after the successful completion of pre-determined milestones in a Phase I trial. Verastem selected GFH375/VS-7375, an oral KRAS G12D (ON/OFF) inhibitor, as its lead program from the collaboration, in December 2023 and the license for GFH375 that was exercised in January 2025 is the first one from this collaboration. The licenses would give Verastem development and commercialization rights outside of China while GenFleet would retain rights inside of China.
