GenFleet Therapeutics (GENFLEET-B, 02595) reported new clinical results for its oral KRAS G12D inhibitor GFH375 at the 2026 American Society of Clinical Oncology (ASCO) annual meeting. The presentation highlighted preliminary monotherapy efficacy in heavily pre-treated patients with cholangiocarcinoma (CCA) and colorectal cancer (CRC), alongside a manageable safety profile and advancing combination-therapy plans.
Cholangiocarcinoma efficacy • Twenty KRAS G12D-mutant CCA patients, 85 % of whom were stage IV and 75 % previously exposed to ≥2 lines of therapy, received 400 mg or 600 mg QD. • Overall response rate (ORR) reached 40 %, disease control rate (DCR) 95 %, and median progression-free survival (mPFS) 6.20 months across all doses. • At the recommended phase II dose (RP2D) of 600 mg, ORR improved to 44.4 % and DCR to 94.4 % among 18 evaluable patients. Median overall survival (mOS) was not yet reached.
Colorectal cancer efficacy • Forty-one KRAS G12D-mutant CRC patients (all stage IV; 95.1 % with ≥2 prior therapies) were enrolled; 35 were evaluable for response after receiving 400–750 mg QD. • Stable disease or partial response was observed in 77.1 % (27/35) of evaluable patients, with 11 % achieving ≥30 % tumor reduction. • mPFS was 4.10 months and mOS reached 10.30 months, indicating meaningful monotherapy activity and supporting further exploration in combination regimens.
Safety and tolerability GFH375 demonstrated a mean relative dose intensity of 98.5 %. The majority of treatment-related adverse events (TRAEs) were Grade 1–2, most commonly diarrhea, nausea, vomiting, anemia and elevated AST. No new safety signals emerged compared with prior studies.
Development status GFH375 is the first oral KRAS G12D inhibitor to enter phase III trials, targeting metastatic pancreatic cancer, and has secured two Breakthrough Therapy Designations in China for pancreatic and non-small cell lung cancers. A phase Ib/II study combining GFH375 with cetuximab for CRC and other solid tumors is underway in China, with data releases planned for future conferences.
Corporate context GFH375 (also licensed as VS-7375) was selected by U.S. partner Verastem in December 2023 under an R&D collaboration granting Verastem ex-China rights. GenFleet retains China rights.
Regulatory reminder GenFleet reiterated that successful development and commercialization of GFH375 cannot be guaranteed and advised investors to exercise caution.
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