Verastem Oncology Gets U.S. IND Approval for VS-7375, Starting Phase 1/2a Trials in Advanced Tumors

Verastem Oncology, a biopharmaceutical enterprise focused on developing treatments for RAS/MAPK pathway-driven cancers, has made significant progress in its efforts to address critical unmet needs in cancer therapy. On April 23, 2025, the company announced that the U.S. Food and Drug Administration (FDA) has approved its Investigational New Drug (IND) application for VS-7375, an innovative oral inhibitor targeting the KRAS G12D mutation, for clinical trials. This approval sets the stage for a Phase 1/2a trial in the United States scheduled to begin in mid-2025. The study aims to explore the drug's safety and efficacy in combating advanced solid tumors, including pancreatic, colorectal, and non-small cell lung cancers.

The development of VS-7375 represents a promising advancement, particularly given that KRAS G12D is the most common KRAS mutation found in human cancers. This mutation is prevalent in a significant percentage of pancreatic, colorectal, endometrial, and non-small cell lung cancers. At present, there are no FDA-approved therapies specifically targeting KRAS G12D mutations. Verastem Oncology's approach with VS-7375, which employs a dual ON/OFF inhibition mechanism, has the potential to produce more profound and lasting responses in cancer treatment.

In collaboration with GenFleet Therapeutics, Verastem has been building on initial research conducted in China. This partnership has already yielded promising results in the preliminary dose escalation phase of the trial, with oral bioavailability confirmed and no dose-limiting toxicities observed at six different dose levels. Notably, some patients with pancreatic and advanced lung cancers have shown partial responses. These findings will be presented by GenFleet at the upcoming 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, scheduled from May 30 to June 3 in Chicago, Illinois.

GenFleet Therapeutics has played a crucial role in advancing the development of VS-7375. The collaboration between the two companies focuses on three oncology discovery programs aimed at addressing RAS/MAPK pathway-driven cancers. As part of this partnership, Verastem holds an exclusive option to license the compounds after achieving specific milestones in Phase 1 trials. VS-7375, also known as GFH375 in China, was selected as the lead program in December 2023, and the corresponding license was exercised in January 2025. This agreement grants Verastem rights to develop and commercialize the drug outside GenFleet's territories, which include mainland China, Hong Kong, Macau, and Taiwan.

The upcoming Phase 1/2a study in the United States will incorporate findings from GenFleet's research to expedite the trial process. By leveraging an effective dose identified in initial studies, Verastem plans to conduct dose escalation trials and assess the compound's efficacy and safety as both a standalone treatment and in combination with other therapies.

Verastem Oncology continues to prioritize the development of innovative small-molecule drugs targeting critical cancer signaling pathways. The company's commitment to addressing the needs of patients with RAS/MAPK pathway-driven cancers remains at the forefront of its research and development efforts.

Overall, the approval of the IND application for VS-7375 marks a significant milestone for Verastem, and the forthcoming clinical trials hold promise for advancing cancer treatment options. As the company moves forward, it remains focused on its mission to bring novel therapies to patients in dire need of effective treatment solutions.