GenFleet Therapeutics (Shanghai) Inc. (GenFleet, HKEX: 02595) disclosed a series of encouraging clinical updates for its first-in-class oral KRAS G12D inhibitor GFH375—licensed ex-China to U.S. partner Verastem Oncology as VS-7375—highlighting rapid progression into global late-stage development across several RAS-mutant solid tumours.
Breakthrough Therapy Momentum in China • The National Medical Products Administration has already granted three Breakthrough Therapy Designations to GFH375 for KRAS G12D-mutant pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). • Monotherapy programmes have transitioned into two registrational Phase III studies for PDAC and NSCLC, positioning GFH375 as the world’s first oral KRAS G12D inhibitor to reach Phase III in these indications.
China Combination Data – GFH375 + Cetuximab • In study GFH375X1202, a twice-weekly cetuximab (500 mg/m²) plus daily GFH375 (600 mg) regimen produced an overall response rate (ORR) of 44 % and a disease control rate (DCR) of 89 % among 54 heavily pre-treated CRC patients (94 % received ≥3rd-line therapy). Median progression-free survival (PFS) reached 7.30 months, with a 4-month PFS rate of 78 %. • In 24 treatment-naïve PDAC patients, the same combination achieved a 71 % ORR and 100 % DCR; 21 patients remained on therapy at the September 16 data cut. • Across 78 evaluable CRC and PDAC patients, treatment-related adverse events were predominantly Grade 1–2 gastrointestinal or dermatologic; no Grade 4/5 events or treatment-related discontinuations were observed.
International Progress with Verastem • In a Phase I monotherapy trial of VS-7375 (900 mg once daily) for previously treated PDAC, 22 patients achieved a confirmed ORR of 41 % and a DCR of 86 % after a median 6.4-month follow-up; two complete responses were recorded. Among eight second-line patients, ORR improved to 50 %. • Safety analysis in 48 solid-tumour patients showed a 97 % median relative dose intensity, with mainly low-grade gastrointestinal adverse events and no significant cytopenias or hepatic toxicity. • Verastem has secured alignment with the U.S. FDA on a registrational, first-line Phase III PDAC trial starting by end-2026. The study will test VS-7375 (900 mg QD) plus either anti-EGFR therapy or chemotherapy (nab-paclitaxel/gemcitabine or mFOLFIRINOX) with dual primary endpoints of PFS and ORR and overall survival as a secondary endpoint. Phase 2 registration-directed studies in NSCLC and CRC are also under way.
Strategic Implications GFH375/VS-7375’s rapid progression—from multiple Breakthrough Therapy Designations in China to imminent global Phase III trials—underscores GenFleet’s potential to deliver the first approved oral therapy targeting KRAS G12D. Robust response rates in late-line CRC, high activity in first-line PDAC, and a benign safety profile reinforce the candidate’s clinical promise. Pending successful Phase III outcomes, GFH375/VS-7375 could offer a differentiated, potentially chemo-free option for patients with RAS-mutant solid tumours worldwide.
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