GenFleet Therapeutics (2595.HK), a commercial-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, announced the initiation of registrational phase III study (GFH375X1301) for GFH375, an oral KRAS G12D (ON/OFF) inhibitor, in patients with pretreated KRAS G12D-mutated metastatic pancreatic cancer. The trial has been initiated at Peking University Cancer Hospital, building on GFH375’s position as one of the fastest advancing oral KRAS G12D inhibitors in clinical development.
Multiple trials evaluating GFH375 (known as VS-7375 outside of China) as monotherapy and in combination regimens are currently underway by GenFleet in China and by GenFleet’s partner Verastem Oncology outside of China; these include a China-based trial investigating GFH375 in combination with chemotherapy (albumin-bound paclitaxel and gemcitabine, AG) as first-line treatment of advanced pancreatic ductal adenocarcinoma (PDAC). In addition, GFH375/VS-7375 has been granted Fast Track Designation by the U.S. FDA for locally advanced and metastatic KRAS G12D-mutated PDAC across all lines of settings.
This multicenter, open-label, randomized and controlled study (GFH375X1301) will be conducted across about 40 sites and plans to enroll approximately 320 metastatic pancreatic cancer patients who had received at least one prior standard systemic therapy. According to Frost & Sullivan, the global incidence of pancreatic cancer is projected to exceed 770,000 new cases in 2037, highlighting the disease as an aggressive malignancy with a five-year survival rate below 10%. Current standard-of-care relies largely on chemotherapy, with objective response rates of only 10–20% in second- and third-line settings and no established standard regimen beyond third line. Nearly 40% of pancreatic cancer patients harbor KRAS G12D mutation, yet no targeted therapy for this mutation has been approved worldwide. KRAS G12D is an independent prognostic biomarker associated with poor response rate and overall survival in PDAC; the KRAS mutation also plays a vital role in regulatory T-cell (Treg) conversion, potentially contributing to an immune-suppressive tumor microenvironment and reducing the response to immune checkpoint inhibitors.
“This is the first-in-world registrational clinical study of an oral KRAS G12D inhibitor for the treatment of pancreatic cancer. It is a significant milestone that underscores our strength in clinical research and operation, as well as GenFleet’s integrated development to build a leading-edge RAS-targeted matrix. GFH375, which entered clinical stage last year, has already generated promising phase I/II monotherapy data this year and moved ahead into multiple trials as monotherapy and in combination regimens. We look forward to a positive outcome from this registrational study (GFH375X1301) to benefit patients. We also anticipate further breakthroughs from other assets in our RAS-targeted matrix, complemented by our cachexia-targeting bispecific antibody therapy, together shaping a synergistic portfolio against pancreatic cancer.”stated Yu Wang, M.D.,Ph.D., Chief Medical Officer of GenFleet.
