Verastem Oncology's VS-7375 Fast-Tracked for KRAS G12D Pancreatic Cancer

Verastem Oncology, a biopharmaceutical firm focused on developing innovative treatments for cancers driven by the RAS/MAPK pathway, has received a significant regulatory boost from the U.S. Food and Drug Administration (FDA). The company announced that its investigational drug, VS-7375, has been granted Fast Track Designation (FTD) for two critical applications: as a first-line treatment for patients with KRAS G12D-mutated locally advanced or metastatic pancreatic adenocarcinoma, and for those with the same mutation who have undergone at least one prior systemic treatment.

The Fast Track process is designed to expedite the development and review of drugs that address serious conditions and fill unmet medical needs. This FDA designation for VS-7375 emphasizes its potential as a breakthrough therapy for a mutation that currently lacks approved targeted treatments. Verastem Oncology's President and CEO, Dan Paterson, highlighted the importance of this designation, especially given the absence of FDA-approved therapies targeting KRAS G12D mutations for patients.

Verastem is currently enrolling patients for a Phase 1/2a clinical trial in the U.S. to evaluate the safety and effectiveness of VS-7375 in advanced KRAS G12D mutant solid tumors, including pancreatic cancer. The study began with a monotherapy dose escalation phase, starting at a 400mg daily dose, informed by promising results from a Phase 1/2 study conducted in China by GenFleet Therapeutics, Verastem's partner. Initial findings presented at the American Society of Clinical Oncology (ASCO) revealed encouraging safety and efficacy data, fueling optimism about the drug's potential.

Looking ahead, Verastem plans to explore higher dose levels of VS-7375, building on the positive outcomes observed in GenFleet’s study. Once the dose-escalation phase is completed successfully, the company will determine the optimal Phase 2 dose and further investigate the monotherapy's efficacy in patients with advanced pancreatic cancer and non-small cell lung cancer. Simultaneously, the company will assess the combination of VS-7375 with cetuximab, an established cancer therapy, in advanced solid tumors. If early results are promising, Verastem intends to launch a combination expansion cohort focusing on colorectal cancer.

The mutation targeted by VS-7375, KRAS G12D, is notably prevalent, representing 26% of all KRAS mutations found in human cancers. This mutation is most frequently identified in pancreatic, colorectal, endometrial, and non-small cell lung cancers. Despite its prevalence, no specific treatments have been approved by the FDA for KRAS G12D mutations, underscoring the importance of Verastem's efforts.

VS-7375 stands out as a potent and selective oral inhibitor, designed to target the KRAS G12D mutation both in its active and inactive states. This drug is a product of Verastem's collaborative efforts with GenFleet Therapeutics, which involve multiple oncology programs focused on RAS/MAPK pathway cancers. The collaboration grants Verastem exclusive rights to develop and commercialize these compounds outside of GenFleet's primary markets in China and its territories.

Verastem's journey with VS-7375 began with the clearance of their Investigational New Drug (IND) application by the FDA in April 2025, leading to the initiation of the Phase 1/2a clinical trial in June 2025. GenFleet's IND for the same compound, known in China as GFH375, was approved a year earlier, with the first patient dosed in July 2024.

The collaboration between Verastem and GenFleet Therapeutics aims to push the boundaries of cancer treatment by focusing on the RAS/MAPK pathway, with VS-7375 emerging as a promising candidate in this endeavor. Verastem Oncology remains committed to developing novel therapies that improve the lives of individuals battling these challenging cancers.