GenFleet Therapeutics, a commercial-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, announced that phase I/II data of GFH375 treating advanced pancreatic ductal adenocarcinoma (PDAC) patients with KRAS G12D mutation were featured in a late-breaking abstract (LBA) for oral presentation at the ESMO Congress 2025 in Berlin on Oct. 19 local time. The latest data demonstrated promising efficacy and manageable safety profile of GFH375 at 600 mg QD (RP2D) in PDAC patients. Among 59 heavily pretreated patients with advanced disease (nearly 70% in the third- or later-line setting) who had their first dose at least 4 months prior to data cut-off date and finished at least one post-treatment tumor assessment: the objective response rate was 40.7%; the disease control rate was 96.7%; the median progression-free survival (PFS) was 5.52 months and the 4-month OS rate was 92.2%.
The G12D variant represents the dominant KRAS mutation subtype (~30% of all KRAS mutations), and it’s projected by Frost Sullivan to affect nearly 1.38 million new cancer cases globally in 2025. The high incidence of the KRAS G12D mutation in pancreatic cancer (~40%), as documented in the scientific literature, translates to a substantial population with crucial unmet needs. 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. Preliminary data from GFH375 monotherapy trial in solid tumor patients were already featured in 2025 as LBA and in presentation sessions at major academic conferences including ASCO and WCLC.
LBA title: Efficacy and Safety of GFH375 Monotherapy in Previously Treated Advanced KRAS G12D Mutant Pancreatic Ductal Adenocarcinoma (PDAC)
Presenter: Prof. Aiping Zhou, Cancer Hospital of the Chinese Academy of Medical Sciences
Abstract No.: LBA84
As of September 27, 2025, a total of 66 patients were enrolled with advanced KRAS G12D mutant PDAC and all received first dose of GFH375 for at least 4 months prior to the data cut-off date: most enrolled patients (95.5%) were diagnosed with stage IV disease at baseline, with metastases most frequently occurring in the liver (78.8%), lung (28.8%) and peritoneum (28.8%); 68.2% of patients had received at least two prior lines of therapy, primarily chemotherapies, and 1/3 of patients had been treated with immunotherapy.
A total of 59 patients had at least one post-treatment tumor assessment: the objective response rate (ORR) was 40.7%; the disease control rate (DCR) was 96.7%; the majority (91.5%) had reduction in target lesions. With a median follow-up time of 5.65 months, the median progression-free survival (mPFS) was 5.52 months with the 4-month PFS rate being 78.2%. As of the data cutoff date, the median overall survival (OS) was not reached with the 4-month OS rate being 92.2%.
As of the data cutoff date (Aug. 27, 2025), GFH375 presented a manageable safety profile in this cohort: most frequent treatment-related adverse events (TRAEs) were diarrhea, decreased neutrophil count, and vomiting; most TRAEs were grade 1 or 2 and manageable with supportive treatment; grade≥3 TRAEs occurred in 31.8% of patients, including only one case of grade 4 (the patient experienced treatment-related neutropenia and recovered with treatment of G-CSF). No grade 5 TRAE was reported.
“Since the IND approval in June 2024, GFH375 monotherapy trial has achieved rapid advancement and encouraging efficacy. For KRAS G12D-mutant patients, a population with substantial medical needs, we are pursuing further breakthroughs through the planning of pivotal studies in late-line setting and combination regimens in frontline setting.”stated Yu Wang, M.D.,Ph.D., Chief Medical Officer of GenFleet.
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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