GenFleet Therapeutics (2595.HK) announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to GFH375/VS-7375 for the treatment of adult patients with KRAS G12D-mutated unresectable locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received platinum-based chemotherapy and an anti-PD-(L)1 antibody either concurrently or sequentially. The oral KRAS G12D (ON/OFF) inhibitor was previously granted with FDA’s FTD for the treatment of KRAS G12D-mutant pancreatic ductal adenocarcinoma (PDAC) in 2025. Besides, GFH375 received the first two Breakthrough Therapy Designations in China for monotherapy treating G12D-mutant pancreatic cancer and NSCLC respectively.
GenFleet obtained the IND approval in China for a phase I/II trial of GFH375 monotherapy in KRAS G12D-mutant solid tumors in June 2024, and GFH375 entered the world’s first phase III registrational trial for oral KRAS G12D inhibitor treating pancreatic cancer last year; additionally, a phase Ib/II clinical trial of two combination regimens was started, in which GFH375 combined with chemotherapy enrolls first-line PDAC patients, and GFH375 in combined with cetuximab enrolls patients with solid tumors including PDAC and colorectal cancer (CRC). The clinical data of GFH375 monotherapy across multiple cancer types including PDAC, NSCLC, cholangiocarcinoma and CRC have been consecutively selected for oral presentations or late-breaking abstracts at annual meetings of ASCO, WCLC and ESMO since last year, demonstrating its promising efficacy and clinical potential in combinational regimens.GFH375/VS-7375 advanced into a phase I/IIa trial last year in the U.S. by GenFleet's partner Verastem Oncology. Multiple single-agent and combinational trials are ongoing in the U.S., and the monotherapy trial for KRAS G12D-mutant solid tumors has cleared several dose levels without dose-limiting toxicities or drug-related liver function test abnormalities. 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.
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.
Forward-looking Statements
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