GENFLEET-B(02595): GFH375 Two globally pioneering combined therapies for pancreatic cancer enter Phase II trials, including a RAS-targeted drug combined with a dual antibody scheme for cachexia and a dual RAS inhibitor scheme with different mechanisms of action.

GENFLEET-B (02595) announced that its board of directors is pleased to declare the recent launch of a three-arm parallel controlled Phase II clinical study of GFH375 (an oral KRAS G12D ON/OFF inhibitor). GFH375 will enter into two new combination therapy regimens to be compared against monotherapy in the Phase II study, targeting patients with KRAS G12D mutant locally advanced unresectable or metastatic pancreatic cancer. This multicenter, open-label, randomized controlled study will be conducted at numerous centers across mainland China, with the lead center being Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine. The two combination regimens included in the study are GFH375 combined with the worlds first dual antibody for cachexia GFS202A (GDF15/IL-6 dual antibody) and GFH375 combined with GFH276 (pan-RAS ON inhibitor). In February 2026, GFH375/VS-7575 received breakthrough therapy designation in China for monotherapy in KRAS G12D mutant metastatic pancreatic cancer, and it has also been granted Fast Track designation by the U.S. FDA in 2025 for treating KRAS G12D mutant metastatic pancreatic ductal adenocarcinoma (PDAC). The KRAS G12D mutation occurs in about 40% of pancreatic cancer patients, and the incidence of cachexia in pancreatic cancer patients is the highest among all cancer types, exceeding 60%. A recent feature report published in Nature focused on the treatment status of patients with pancreatic cancer cachexia and presented observational studies involving nearly a thousand cancer patients as part of the multinational cachexia research initiative CANCAN (Cancer Cachexia Action Network, spearheaded by the National Cancer Institute of the USA and the Cancer Research UK). In addition to revealing the association between elevated GDF15 and tumors as well as cachexia, several fundamental studies cited in the article indicate that elevated GDF15 may anomalously link tumor, immune, and brain pathological interactions, becoming a significant cause of symptoms such as weight loss and treatment intolerance; meanwhile, increased levels of inflammatory factor IL-6 can lead to decreased dopamine release, consequently inhibiting feeding and behavior in mice. Clinical trial results of overseas GDF15 monoclonal antibodies or IL-6 monoclonal antibodies in combination with standard treatment for PDAC suggest significant improvements in patient constitution and treatment tolerance, or enhancements in anti-tumor efficacy and overall survival rates; the combination of KRAS G12D inhibitors with cachexia therapies is expected to yield synergistic effects. GFH375 has entered the world's first Phase III registration study of an oral KRAS G12D inhibitor (monotherapy for metastatic pancreatic cancer); preliminary research data for GFS202A was also selected for poster presentation at the ASCO annual meeting in 2026, demonstrating excellent safety and therapeutic potential, with patient appetite improvement, and dose-dependent increases in weight and skeletal muscle content. In addition, the combination of selective and pan-RAS inhibitors is expected to achieve deeper and more sustained tumor remission in clinical treatment and delay the onset of resistance; animal studies conducted by the Jinfang research team on KRAS G12D mutant PDAC also showed that the combination of GFH375 and GFH276 surpassed the efficacy of either agent alone. The overseas RAS pathway company Revolution Medicines has initiated clinical trials for the molecular glue KRAS G12D inhibitor (RMC-9805) and pan-RAS inhibitor (RMC-6236) in the treatment of PDAC, with preliminary data presented at the 2026 EMSO GI conference demonstrating objective response rates superior to single-agent therapies.