GenFleet Therapeutics（2595.HK） announced the updated clinical data of GFH375 monotherapy treating KRAS G12D-mutant solid tumors were presented in the oral abstract session at the 2026 American Society of Clinical Oncology (ASCO) annual meeting on June 1 local time. Preliminary efficacy was observed with GFH375 monotherapy in cholangiocarcinoma (CCA) and colorectal cancer (CRC). 20 pretreated patients with CCA harboring KRAS G12D mutation completed at least one post-treatment tumor assessment: the overall response rate (ORR) was 40% and disease control rate (DCR) was 95% across all dose levels, with treatment still ongoing for 5 patients; the ORR reached 44.4% and DCR was 94.4% at the 600 mg QD (recommended phase II dose, RP2D) level in 18 patients. Additionally, the median progression-free survival (mPFS) was 6.2 months across all dose levels.
Among 41 patients with advanced CRC, the mPFS was 4.1 months and the median overall survival (mOS) reached 10.3 months. The preliminary efficacy data demonstrated monotherapy activity of GFH375 and its therapeutic potential in combinational regimens for CRC. A phase Ib/II trial evaluating GFH375 combined with cetuximab for CRC and other solid tumors is ongoing in China, with relevant data expected for presentation at upcoming academic conferences.
“This is the fourth consecutive selection of GFH375's clinical data for oral presentations at top-tier global academic conferences including annual meetings of ASCO, ESMO and WCLC. GFH375 is the world’s first oral KRAS G12D inhibitor progressing into phase III study for metastatic pancreatic cancer. It has been granted with China’s first two Breakthrough Therapy Designations for KRAS G12D inhibitor monotherapy, in G12D-mutant pancreatic cancer and non-small cell lung cancer respectively. We are encouraged by its therapeutic potential in diverse tumor types and look forward to more positive results from subsequent monotherapy and combinational investigations.”stated Yu Wang, M.D., Ph.D.,Chief Medical Officer of GenFleet.
Preliminary Efficacy of GFH375 in Patients with Advanced Cholangiocarcinoma or Colorectal Cancer Harboring KRAS G12D Mutation (Abstract No.: 3008)
Presented by Prof. Zhengbo Song, Zhejiang Cancer Hospital
As of data cutoff date, a total of 20 KRAS G12D-mutant CCA patients received GFH375 treatment; 85% of them were diagnosed as stage IV at baseline, with most frequent metastases occurring in liver (70%) and lung (40%); 75% had received at least two prior lines of therapy; 85% had been previously treated with immunotherapy. The 20 patients were orally administered with GFH375 at 400 mg or 600 mg QD and all of them completed at least one post-treatment assessment: target lesion shrinkage was observed in 18 patients; 40% achieved tumor reduction by at least 30%, including one case of complete response. The mPFS was 6.2 months, and the mOS was not reached.
A total of 41 patients with KRAS G12D-mutant CRC were diagnosed as stage IV at baseline, with most frequent metastases occurring in lung (82.9%) and liver (56.1%); 95.1% had received at least two prior lines of therapy. 35 CRC patients received treatment of GFH375 monotherapy at 400-750 mg QD and finished at least one post-treatment assessment: 27 patients achieved stable disease or partial response; 11% achieved tumor reduction by at least 30%, with treatment still ongoing for 2 patients. The mPFS was 4.1 months, and the mOS was 10.3 months.
As of data cutoff date, GFH375 monotherapy demonstrated a manageable safety/tolerability profile in both CCA and CRC patients, with a mean relative dose intensity of 98.5%. The majority of treatment-related adverse events (TRAEs) were graded 1-2, in which the patients recovered with supportive treatment; the most common TRAEs occurring in ≥10% patients included diarrhea, nausea, vomiting, anemia and increased AST, etc. The incidence of TRAEs was comparable to that of treatment-emergent adverse events (TEAEs) throughout treatment, and no new safety signals appeared relative to previously reported safety data of GFH375 monotherapy for other solid tumors.
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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