GenFleet Therapeutics (HKG: 2595) announced, in a voluntary disclosure, positive progress in the clinical development of GFH375/VS‑7375, its orally active, highly selective small‑molecule KRAS G12D inhibitor, with latest data from multiple studies in China and abroad. In China, GFH375 has received three Breakthrough Therapy Designations (BTD) and advanced into two registrational Phase III studies in pancreatic cancer and NSCLC; overseas partner Verastem Oncology has reached alignment with the U.S. FDA on a registrational Phase III design and plans to open the world’s first front‑line, chemo‑free Phase III study of a KRAS G12D inhibitor combined with anti‑EGFR therapy by year end.
Regulatory & Development Milestone
| Item | Detail |
|---|---|
| Company | GenFleet Therapeutics (HKG: 2595) |
| Overseas Partner | Verastem Oncology (“Verastem”) |
| Product | GFH375 / VS‑7375 – oral selective KRAS G12D (ON/OFF) inhibitor |
| China BTD | 3 designations – KRAS G12D‑mutant pancreatic cancer, NSCLC, CRC |
| China Phase III | 2 registrational Phase III monotherapy studies – pancreatic cancer & NSCLC |
| Overseas Phase III | Registrational front‑line PDAC study planned to open by end of 2026 (VS‑7375 + anti‑EGFR or chemo – AG or mFOLFIRIRINOX) |
| FDA Alignment | Verastem aligned with FDA on Phase III design – PFS & ORR dual primary, OS secondary |
| Rights Split | Verastem – rights outside China; GenFleet – rights within China |
Drug Profile & Mechanism of Action
- Molecule: Orally active, highly selective small‑molecule KRAS G12D (ON/OFF) inhibitor.
- Binding Mode: Binds KRAS G12D non‑covalently, disrupting activation of downstream signaling and effectively inhibiting tumor cell proliferation.
- Selectivity: Preclinical data showed dose‑dependent inhibition in KRAS G12D models and low off‑target risk in kinase selectivity and safety assays.
- First‑Mover Status: GFH375 is described as the world’s first oral KRAS G12D inhibitor to enter Phase III for NSCLC and pancreatic cancer.
Clinical Evidence – China Combination Study (GFH375X1202)
Regimen: GFH375 600 mg QD + cetuximab 500 mg/m² Q2W (data as of 16 Sep 2026).
| Cohort | Patients | ORR | DCR | Median PFS | Notes |
|---|---|---|---|---|---|
| Pretreated CRC | 54 (≥1 assessment) | 44 % | 89 % | 7.3 months (5.4‑mo follow‑up) | 4‑mo PFS rate 78 %; 100 % distant mets; 94 % ≥3rd‑line, 50 % ≥4th‑line |
| First‑line PDAC | 24 (treatment‑naïve) | 71 % | 100 % | Not disclosed | 96 % distant mets; 21 patients remained on treatment |
Safety (as of 22 Jul 2026; 78 CRC/PDAC patients): Favorable, manageable profile – most common TRAEs were diarrhea, vomiting, nausea and rash, mostly Grade 1–2. No TRAE‑related discontinuations; no Grade 3 TRAE >5 %; no Grade 4–5 TRAEs. Cutaneous toxicities were consistent with published cetuximab/EGFR‑antibody profiles. No new safety signals versus GFH375 monotherapy, no overlapping toxicities, and preliminarily lower frequency/severity of hepatic and hematologic TRAEs than late‑line monotherapy.
Clinical Evidence – Overseas VS‑7375 Monotherapy (Verastem)
Second‑line+ PDAC (900 mg QD; data as of 7 Oct 2026):
| Metric | Result |
|---|---|
| Patients (≥2nd‑line, ≥1 dose) | 22 |
| Confirmed ORR (cORR) | 41 % (median follow‑up 6.4 months) |
| DCR | 86 % |
| Complete Responses | 2 (1 confirmed; 1 still on treatment) |
| On Treatment | 16 / 22 |
| 2nd‑line Subgroup (8/22) | cORR 50 % |
Safety (as of 29 Sep 2026; 48 solid‑tumor patients, 900 mg QD): Median relative dose intensity 97 %; favorable and manageable. TRAEs were primarily low‑grade GI (nausea, vomiting, diarrhea), mostly controlled with standard supportive care. No clinically meaningful cytopenias or liver abnormalities; no cumulative toxicity with long‑term dosing; no overlapping AEs with anti‑EGFR therapy. VS‑7375 monotherapy and combination regimens are also being evaluated in Phase 2 registration‑directed trials for NSCLC and CRC.
Market Impact & Outlook
- KRAS G12D Leadership: As the first oral KRAS G12D inhibitor in Phase III (NSCLC and pancreatic cancer), GFH375/VS‑7375 targets one of oncology’s historically “undruggable” mutations across large solid‑tumor populations.
- Global Dual‑Track: A synchronized China (GenFleet) + overseas (Verastem) registrational strategy spans monotherapy and multiple combinations – anti‑EGFR, AG, mFOLFIRINOX – across PDAC, NSCLC and CRC.
- Combination Signal: Early ORR of 71 % in first‑line PDAC and 44 % in heavily pretreated CRC with cetuximab suggests the chemo‑free combination could become a differentiated front‑line option.
- Near‑Term Catalyst: Verastem’s planned front‑line Phase III opening by year‑end 2026, aligned with the FDA, is the next major milestone.
Forward‑Looking Statements
This brief contains forward‑looking statements regarding clinical data, registrational trial initiation, regulatory alignment and commercialization expectations for GFH375/VS‑7375. Under HKEX Listing Rule 18A.05, GenFleet cannot guarantee successful development or marketing of the product. Actual results may differ materially due to scientific, regulatory, market and R&D uncertainties; shareholders and potential investors are advised to exercise caution.-Fineline Info & Tech
