GENFLEET-B(02595): GFH375 clinical trial for the treatment of metastatic pancreatic cancer initiated at the first research center. It is the world's first Phase III study comparing oral KRAS G12D inhibitor monotherapy to chemotherapy.

GENFLEET-B(02595) announced that the oral KRAS G12D (ON/OFF) inhibitor GFH375 has started a registration Phase III trial (GFH375X1301) for the treatment of recurrent KRAS G12D mutant metastatic pancreatic cancer patients at Peking University Cancer Hospital. Currently, the development progress of GFH375 is at the forefront of global oral KRAS G12D inhibitors. Multiple GFH375 (VS-7375 outside China) monotherapy and combination therapies are being clinically explored in China (led by GenFleet) and overseas (led by GenFleet's partner Verastem Oncology), including GFH375 combination chemotherapy (albumin paclitaxel and gemcitabine, AG) as first-line treatment for advanced pancreatic ductal adenocarcinoma (PDAC). Additionally, GFH375/VS-7375 have received FDA Fast Track designation for the treatment of locally advanced and metastatic KRAS G12D mutant PDAC patients. This multicenter, open-label, randomized Phase III trial (GFH375X1301) will be conducted at approximately 40 centers and plans to enroll around 320 recurrent metastatic pancreatic cancer patients who have received at least one standard systemic treatment. According to Sullivan data, there will be over 770,000 new cases of pancreatic cancer globally in 2037, with a high malignancy and poor prognosis, and a 5-year survival rate of less than 10%. Currently, pancreatic cancer treatment still relies mainly on chemotherapy drugs, with a second-line to third-line objective response rate (ORR) of only 10-20%, and there is no standard treatment for third-line and beyond. Research literature shows that nearly 40% of pancreatic cancer patients have a KRAS G12D mutation, and there is currently no approved targeted therapy for this globally; KRAS G12D mutation is an independent prognostic marker for poor response rate and overall survival in advanced PDAC, and plays a key role in regulating T cell transformation, promoting the formation of an immunosuppressive tumor microenvironment and leading to poor response to immune checkpoint inhibitors. Dr. Wang Yubo, Chief Medical Officer of GenFleet, said, "This is the world's first registration clinical study of an oral RAS inhibitor for pancreatic cancer treatment. This important milestone reflects the clinical research and execution capabilities of the GenFleet clinical team, as well as the company's integrated new drug development strength in RAS therapy matrix. GFH375 entered clinical trials last year and has already obtained excellent monotherapy Phase I/II study data this year, and has recently entered multiple monotherapy and combination therapy trials. We look forward to positive results from this registration study (GFH375X1301) and benefiting patients soon. We also look forward to more breakthroughs in the future with GenFleet's RAS-targeted drugs, and forming a synergistic treatment matrix targeting pancreatic cancer with the company's bispecific immunotherapy."