GFH375X1101 is an open label, multicenter study evaluating GFH375 monotherapy in advanced solid tumor patients harboring KRAS G12D mutation. Preliminary phase I data demonstrated good oral bioavailability and anti-tumor activities of GFH375, with encouraging efficacy in treating multiple tumor types including pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC). 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.
As of the data cutoff date, among 49 patients orally administered at daily dosages of 400 or 600 mg: 43 patients who received at least one post-treatment tumor assessment achieved an objective response rate (ORR) of 42% and a disease control rate (DCR) of 91%; the ORR was 52% and DCR was 100% among 23 efficacy-evaluable PDAC patients, and the ORR was 42% and DCR was 83% among 12 efficacy-evaluable NSCLC patients. Pharmacokinetic analysis revealed the dose levels of 400 mg and 600 mg QD were able to achieve average trough concentrations that were three times above the IC90 value for p-ERK inhibition in AsPC-1 cells. Moreover, 600 mg QD has been recommended as the phase II dose (RP2D) for the phase II portion which started in February 2025.
As of the data cutoff date, among the 52 patients across all dose levels and indications who received at least one post-treatment tumor assessment (efficacy evaluable): the overall ORR was 38% and DCR was 90%; 38 patients exhibited reduction in target lesion, and 20 patients achieved partial response. With good oral bioavailability, GFH375 demonstrated antitumor activities among patients of major cancer types like PDAC and those who had experienced disease progression following multiple lines of prior treatments.
Prof. Shun Lu, Dept. of Medical Oncology
Shanghai Chest Hospital
"We are delighted at the encouraging efficacy of GFH375 in treatment of cancer types including PDAC and NSCLC. G12D represents the most prevalent KRAS mutation subtype across multiple solid tumors, and we were impressed by the significant unmet medical needs in patients. We anticipate more positive results from this study that may lead to a life-saving treatment.”
Yu Wang, M.D.,Ph.D.
Chief Medical Officer of GenFleet
About GFH375/VS-7375
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.
Since its inception in 2017, GenFleet has built up industry-leading capabilities and expertise in developing novel drug candidates spanning small molecules and biologics. Its pipeline comprises numerous programs that have advanced to later-stage or pivotal clinical trials across China, the United States and Europe. Dupert® (fulzerasib) is the first approved KRAS G12C inhibitor in China and the third globally; it also received NDA priority review designation and two breakthrough therapy designations. Additionally, the first-line combination therapy of fulzerasib and cetuximab has progressed into phase II study in Europe, marking the world's first integration of KRAS and EGFR inhibitors for first-line non-small cell lung cancer treatment.
With proven success in developing RAS-pathway targeted therapies, GenFleet is also vigorously expanding its portfolio that includes other innovative therapies and novel modalities. Furthermore, it's strengthening its commercial collaborative network through strategic out-licensing agreements or clinical cooperations with prestigious listed companies across the world.
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