GenFleet Therapeutics, a commercial-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, announced it finished dosing of the first patient in a phase Ib/II trial of GFH375 (known as VS-7375 outside of China), combination study treating KRAS G12D-mutant patients with solid tumors. China’s National Medical Products Administration (NMPA) approved the clinical trial application for GFH375 combined with cetuximab or chemotherapy in an open-label, multi-center phase Ib/II study. The regimen of GFH375 combined with chemotherapy will be conducted among first-line pancreatic ductal adenocarcinoma (PDAC) patients.
Phase Ib trial will be conducted at approximately 15 investigational sites including Beijing Cancer Hospital. The primary objectives of the overall study are to evaluate the safety/tolerability, efficacy and pharmacokinetic profile of GFH375 in combination with cetuximab or chemotherapy. In the phase II trial, the combination of GFH375 with chemotherapy (albumin-bound paclitaxel and gemcitabine, AG) will be administered to untreated patients with advanced PDAC, while the combination of GFH375 with cetuximab (EGFR antibody) will be used for patients with advanced PDAC or colorectal cancer (CRC).
“We are encouraged that the dual combination regimens have entered the clinical stage. Notably, the inclusion of a first-line PDAC treatment will expand GFH375's clinical development from later-line to frontline settings. The potential of GFH375 across major cancer types was highlighted at several global academic conferences, with monotherapy data in PDAC and NSCLC orally presented as LBA at ESMO and WCLC respectively. We look forward to the continued clinical progress of this GFH375 to benefit patients.”stated Yu Wang, M.D.,Ph.D., Chief Medical Officer of GenFleet.
China’s NMPA granted the IND clearance for GFH375 for a phase I/II monotherapy study in June 2024, followed by the U.S. FDA’s Fast Track Designation this year for GFH375/VS-7375 treating locally advanced or metastatic PDAC with KRAS G12D mutation across all lines of therapy.
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.
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