GenFleet Therapeutics (Shanghai) Inc. (Stock Code: 2595) presented phase I/II data on its oral KRAS G12D (ON/OFF) inhibitor, GFH375, in pancreatic ductal adenocarcinoma (PDAC) at the ESMO Congress 2025 in Berlin on October 19, 2025. The presentation highlighted results in heavily pretreated patients with advanced KRAS G12D-mutant PDAC, with the recommended Phase II dose established at 600 mg once daily.

Efficacy results in 59 patients included an objective response rate of 40.7%, accompanied by a disease control rate reaching 96.7%. A median progression-free survival of 5.52 months was observed, and the 4-month overall survival rate stood at 92.2%. Most patients (91.5%) experienced a reduction in target lesions. The median overall survival had not been reached by the data cutoff.

Safety data revealed that the most frequent treatment-related adverse events were diarrhea, decreased neutrophil count, and vomiting, which were predominantly grade 1 or 2 in severity. Only one grade 4 event was noted, and there were no grade 5 events reported. GFH375 has also been granted IND clearance by the NMPA in June 2024, followed by an FDA Fast Track Designation for advanced or metastatic PDAC with KRAS G12D mutation. The compound emerged from a collaboration between GenFleet and Verastem, with Verastem having development and commercialization rights outside of China.