Verastem: GFH375 resulted in 41% ORR in Phase 1/2 study

Verastem (VSTM) Oncology on Sunday announced updated efficacy and safety data from partner GenFleet Therapeutics’ Phase 1/2 monotherapy study in China of GFH375, an oral KRAS G12D inhibitor for patients with KRAS G12D mutant advanced pancreatic ductal adenocarcinoma. Among 59 heavily pre-treated patients with advanced disease, who received two or more prior lines of therapy, an overall response rate of 41% was achieved at the monotherapy recommended Phase 2 dose of 600 mg daily. The updated data were featured in a late-breaking abstract for oral presentation by GenFleet Therapeutics at the European Society for Medical Oncology Congress 2025 on October 19, 2025, in Berlin, Germany. GenFleet reported that 66 patients with advanced KRAS G12D mutant PDAC were treated with 600 mg QD of GFH375 monotherapy. In the study, 95.5% of patients were diagnosed with stage IV disease at study entry, and 68.2% of patients had received at least two prior lines of anticancer therapies, with 92.4% of patients receiving gemcitabine-based regimens and more than 50% receiving fluorouracil or irinotecan-containing regimens. As of the data cutoff of September 27, 2025, 59 efficacy-evaluable patients had at least one post-treatment tumor assessment and achieved an ORR of 40.7% and a disease control rate of 96.7% with the majority of patients experiencing a reduction in target lesions. Overall survival observed at month four was 92.2%. The median OS was not reached as of the data cutoff, with a median follow-up time of 5.65 months. The median progression-free survival was 5.52 months with a median follow-up time of 5.65 months and a 4-month PFS rate of 78.2%. At evaluation, 31 of patients were still on treatment with the longest duration of treatment eclipsing one year. The safety profile in PDAC patients was consistent with the previously reported data at recent medical congresses. As of the data cutoff date of August 27, 2025, the most frequent treatment-related adverse events occurring in greater than or equal to20% of patients included diarrhea, neutrophil count decreased, vomiting, nausea, anemia, white blood cell count decreased, decreased appetite, hypoalbuminemia, platelet count decreased, asthenia, aspartate aminotransferase increased, and alanine transferase increased. Grade 3 TRAEs occurred in 20 patients and a Grade 4 TRAE occurred in one patient. Of the 66 patients in the safety population, four patients had a dose reduction and two patients discontinued due to TRAEs. No TRAE-related deaths were reported. The mean relative dose intensity was 93%. The Phase 1/2a study will be conducted in the U.S., with the potential to expand globally, and will evaluate the safety and efficacy of VS-7375 in patients with advanced KRAS G12D mutant solid tumors. The starting dose for the Phase 1 study of 400 mg is based on the dose identified in the initial data from the GenFleet study to accelerate the trial’s progress. Verastem plans to dose escalate across levels where responses were observed in GenFleet’s study and will assess in the Phase 2a portion the efficacy and safety of VS-7375, both as monotherapy and in combination, in patients with advanced solid tumors, such as pancreatic, colorectal, and non-small cell lung cancers.