Berlin, Germany — October 19, 2025 — Leads & Copy — Verastem Oncology (Nasdaq: VSTM) announced positive, updated efficacy and safety data from partner GenFleet Therapeutics’ Phase 1/2 monotherapy study in China of GFH375, an oral KRAS G12D (ON/OFF) inhibitor (VS-7375 outside of China) for patients with KRAS G12D mutant advanced pancreatic ductal adenocarcinoma (PDAC).
Among 59 heavily pre-treated patients with advanced disease, who received two or more prior lines of therapy, an overall response rate (ORR) of 41% was achieved at the monotherapy recommended Phase 2 dose (RP2D) of 600 mg daily (QD).
The updated data were featured in a late-breaking abstract for oral presentation by GenFleet Therapeutics at the European Society for Medical Oncology (ESMO) Congress 2025 on October 19, 2025, in Berlin, Germany.
According to Verastem Oncology, patients with advanced pancreatic cancer and a KRAS G12D mutation tend to have a worse prognosis compared to other KRAS mutations.
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% (24/59) (confirmed and unconfirmed) and a disease control rate (DCR) of 96.7% (57/59) with the majority of patients (91.5%) experiencing a reduction in target lesions. Overall survival (OS) 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 (PFS) 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 (47%) of patients were still on treatment with the longest duration of treatment eclipsing one year (367 days).
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 (TRAEs) occurring in ≥20% 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 (30.3%) and a Grade 4 TRAE (neutropenia) occurred in one patient (1.5%). Of the 66 patients in the safety population, four patients (6.1%) had a dose reduction and two patients (3%) discontinued due to TRAEs. No TRAE-related deaths were reported. The mean relative dose intensity was 93%.
VS-7375 is a potential best-in-class, potent, and selective oral KRAS G12D dual ON/OFF inhibitor. VS-7375 is the lead program from the Verastem Oncology discovery and development collaboration with GenFleet Therapeutics. Verastem announced in April 2025 that the U.S. Investigational New Drug (IND) application for VS-7375 was cleared and initiated a Phase 1/2a clinical trial in June 2025.
GenFleet’s IND for VS-7375 (known as GFH375 in China) was approved in China in June 2024, and the first patient was dosed in a Phase 1/2 study in July 2024.
The collaboration with GenFleet Therapeutics aims to advance three oncology discovery programs related to RAS/MAPK pathway-driven cancers.
Verastem markets AVMAPKI™ FAKZYNJA™ CO-PACK in the U.S. Our pipeline is focused on novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition, FAK inhibition, and KRAS G12D inhibition.
Dan Paterson, president and chief executive officer of Verastem Oncology, commented on the updated data.
Source: Verastem Oncology
