The U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for VS-7375, an oral KRAS G12D inhibitor developed by Verastem Oncology in collaboration with GenFleet Therapeutics. This clearance paves the way for the initiation of a Phase 1/2a clinical trial focused on treating advanced solid tumors characterized by the KRAS G12D mutation, including pancreatic, colorectal and non-small cell lung cancers.
VS-7375 is a next-generation small molecule designed to inhibit both the active (GTP-bound) and inactive (GDP-bound) forms of the KRAS G12D protein, a mutation present in approximately 26% of KRAS-mutant tumors. This dual mechanism is intended to increase tumor response rates and enhance compatibility with combination therapies, potentially setting a new standard in targeting one of oncology’s most challenging mutations.
The upcoming U.S. trial will build upon promising preclinical and early clinical data from China, where VS-7375 demonstrated good oral bioavailability, no dose-limiting toxicities and partial tumor responses in heavily pre-treated patients with pancreatic and lung cancers. In the Phase 1 portion of the U.S. study, dosing will begin based on efficacious levels identified in GenFleet’s trials, with plans to escalate based on observed responses. The Phase 2a part will assess VS-7375 as both a monotherapy and in combination with other agents.
Importantly, preliminary data on VS-7375’s clinical performance will be presented at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting in Chicago. The rapid oral presentation will offer early insights into the potential of VS-7375 to fill a major therapeutic gap, as there are currently no FDA-approved treatments specifically targeting KRAS G12D mutations.
With this clearance, Verastem and GenFleet aim to address a substantial unmet need, offering hope for patients facing aggressive cancers that historically have had limited targeted treatment options
Disclaimer: This article is for general informational purposes only and is based on publicly available sources as of April 26, 2025. It does not constitute medical advice, diagnosis or treatment. For medical concerns or decisions regarding participation in clinical trials, please consult qualified healthcare professionals.
