GenFleet Therapeutics (2595.HK) today announced positive progress in GFH375/VS-7375’s clinical development with latest data disclosed from multiple studies in China and abroad. In China, GFH375 has received three Breakthrough Therapy Designations (BTD) for treatment of KRAS G12D-mutant pancreatic cancer, non-small cell lung cancer (NSCLC) and colorectal cancer (CRC); GFH375 monotherapy has advanced into two registrational phase III studies in pancreatic cancer and NSCLC. GenFleet’s overseas partner Verastem Oncology has planned to open a registrational phase III study including multiple regimens of VS-7375 in combination with anti-EGFR therapy or chemotherapy, with PFS (progression-free survival) and objective response rate (ORR) serving as dual primary endpoints and overall survival (OS) as secondary endpoint; Verastem has reached alignment with the U.S. Food and Drug Administration (FDA) on the phase 3 study design.
“We are pleased to see the preliminary efficacy of GFH375 in combination with cetuximab treating CRC in China, as well as the encouraging efficacy data of GFH375/VS-7375 demonstrated across multiple overseas trials. GFH375 is the world’s first oral KRAS G12D inhibitor to have entered phase III studies for the treatment of NSCLC and pancreatic cancer. Furthermore, the product is expected to enter the world’s first front-line phase III study overseas, evaluating a KRAS G12D inhibitor in combination with an anti-EGFR therapy (as a first-line chemo-free regimen) by the end of this year. We anticipate more innovative monotherapy and combination regimens of GFH375/VS-7375 will bring hope to global patients.”stated Yu Wang, M.D., Ph.D., Chief Medical Officer of GenFleet.
Preliminary data from a combination study in China: GFH375 plus cetuximab in pretreated CRC and in first-line PDAC
Sponsored by GenFleet, the study (GFH375X1202) includes a combination regimen of GFH375 (600 mg QD) plus cetuximab (500 mg/m² Q2W) that demonstrated encouraging preliminary efficacy and a favorable safety/tolerability profile in patients with pretreated CRC and first-line PDAC.
As of September 16, 2026, 54 CRC patients had completed at least one post-treatment tumor assessment. Among them, 100% had distant metastases (57% with lung metastasis, 50% with liver metastasis, 46% with peritoneal metastasis) upon enrollment; the majority of this CRC cohort were treated in ≥3rd-line setting post-enrollment (94% of all patients received ≥3rd-line treatment, and 50% of all patients received ≥4th-line treatment); the overall ORR was 44% in this cohort, and the disease control rate (DCR) was 89%; the median PFS was 7.3 months (with median follow-up of 5.4 months), the 4-month PFS rate was 78%. In addition, 24 treatment-naïve PDAC patients had completed at least one post-treatment assessment, of whom 96% had distant metastases (liver metastasis 58%, peritoneal metastasis 29%, lung metastasis 14%) upon enrollment; the ORR was 71% and DCR was 100%; 21 patients remained on treatment.
As of July 22, 2026, a total of 78 CRC and PDAC patients demonstrated a favorable safety/tolerability profile after treatment of GFH375 (600 mg QD) in combination with cetuximab (500 mg/m² Q2W). The most common treatment-related adverse events (TRAEs) included diarrhea, vomiting, nausea and rash, mostly Grade 1-2 and generally manageable. No TRAEs-related dose discontinuation occurred; no individual Grade 3 TRAE had an incidence exceeding 5% and there were no Grade 4-5 TRAEs. The cutaneous toxicities observed in this combination regimen were consistent with the published literature on EGFR antibodies, representing common adverse reactions well-recognized for cetuximab. Compared with previously reported GFH375 monotherapy safety data, no new safety signals were identified in GFH375-related data from this combination regimen. No overlapping toxicities between the two agents were observed; preliminary data indicated less frequency and severity of hepatic and hematologic TRAEs compared with late-line GFH375 monotherapy.
Overseas clinical progress of VS-7375 in multiple monotherapy and combination trials; a first-line phase III PDAC study to be opened by year end
Preliminary data from multiple overseas monotherapy and combination trials of VS-7375 sponsored by Verastem also demonstrated promising therapeutic prospects and a favorable safety profile in Caucasian patients across different dose levels.
In the PDAC trial of VS-7375 monotherapy at 900 mg QD, 22 patients were treated in ≥2nd-line setting post-enrollment, with at least one dose of treatment as of data cutoff date; as of October 7, 2026, the confirmed ORR (cORR) was 41% in this patient cohort and the DCR was 86% (with median follow-up of 6.4 months); 2 patients achieved complete responses, with one confirmed and the other still on treatment; the majority of patients (16/22) remained on treatment. The confirmed ORR reached 50% among the 8 patients (8/22) that received 2nd-line treatment post-enrollment. Verastem has planned to open a registrational phase III study in first-line PDAC by the end of 2026, to evaluate VS-7375 at 900 mg QD in combination with anti-EGFR therapy or chemotherapy (AG or mFOLFIRINOX). Additionally, monotherapy or combination regimens of VS-7375 are also being evaluated in phase 2 registration-directed trials for treatment of NSCLC and CRC.
As of September 29, 2026, 48 solid tumor patients were treated with VS-7375 monotherapy at 900 mg QD with a median relative dose intensity level of 97% and demonstrated a favorable and manageable safety profile across tumor types. TRAEs were primarily low-grade gastrointestinal (GI), including nausea, vomiting and diarrhea, and the vast majority were effectively treated with standard supportive care measures; no clinically meaningful cytopenias or liver function abnormalities were reported; compared with previously reported data, no clinically meaningful cumulative toxicity was observed with long-term dosing. There were no overlapping adverse events observed in VS-7375 combined with anti-EGFR therapy; GI TRAEs in the combinations with standard-of-care therapies were comparable to VS-7375 monotherapy, together with no meaningful differences in liver function test elevations or increased risk of hematologic and neuropathy TRAEs.
Reference:
1. Pharmacovigilance analysis of cutaneous adverse drug reactions for cetuximab, panitumumab, and necitumumab based on EudraVigilance and WHO VigiAccess, Frontiers in Pharmacology, 2026
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. Outside of China, GenFleet’s partner Verastem Oncology is evaluating VS-7375 in TARGET-D 202, a registration-directed phase 2 study in NSCLC.
GenFleet received the Breakthrough Therapy Designations granted by China’s CDE in 2026 for GFH375 in pretreated KRAS G12D-mutant NSCLC and metastatic pancreatic cancer respectively; Verastem received the Fast Track Designations granted by U.S. FDA for VS-7375 treating KRAS G12D-mutant pancreatic ductal adenocarcinoma across all lines of therapy in 2025, and treating locally advanced unresectable or metastatic KRAS G12D-mutant NSCLC in 2026.
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