FDA Greenlights VS-7375 Study for Tough-to-Treat KRAS G12D Tumors

• The FDA has cleared the investigational new drug (IND) application of VS-7375, with plans for a phase 1/2a study in mid 2025.
• VS-7375 is a KRAS G12D inhibitor intended for treatment of solid tumors.
• This clearance marks an important step forward in filling unmet needs for KRAS G12D-mutant cancer treatment.

The IND application of VS-7375 (GFH375), an investigational KRAS G12D inhibitor, has been cleared by the FDA, and a phase 1/2a study in patients with advanced solid tumors harboring a KRAS G12D mutationplans to begin enrollment mid 2025.¹

“We’re excited to advance the clinical program for VS-7375 in the US and build on the initial dose escalation work conducted by GenFleet in China that demonstrated oral bioavailability and no dose-limiting toxicities across 6 dose levels, with partial responses achieved among multiple patients with both pancreatic and advanced lung cancers,” said Dan Paterson, president and chief executive officer of Verastem Oncology, manufacturer of VS-7375, in a press release.

“We believe there remains a significant opportunity to improve on the efficacy seen to date with other KRAS G12D-selective agents. VS-7375’s dual inhibition of both the ON/OFF states has the potential to drive deep and durable cancer responses and allow for better combinability with other agents,” added Paterson.

Further, Verastem announced that an abstract on the phase 1/2 dose-escalation study of VS-7375 has been accepted into a rapid oral presentation session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting taking place May 30 to June 3, 2025, in Chicago, Illinois.

VS-7375 was approved in China in June 2024, and the first patient was dosed in the phase 1/2 dose-escalation study in July 2024.

About the Phase 1/2a Study of VS-7375

This new phase 1/2a study of VS-7375 will evaluate the safety and efficacy of VS-7375 in patients with advanced solid tumors harboring a KRAS G12D mutation. In phase 2a, investigators will evaluate VS-7375 as a monotherapy and in combination with other agents in tumors including pancreatic, colorectal, and non–small cell lung cancers.

About KRAS G12D Mutations

KRAS G12D is the most prevalent KRAS mutation in human cancers, representing 26% of all KRASmutations. KRAS G12D mutations are most commonly observed in pancreatic, colorectal, endometrial, and non–small cell lung cancers.

As there are no currently approved therapies in the US specifically targeting KRAS G12D, the clinical development of VS-7375 could prove important in filling gaps in the treatment landscape.

In January 2025, the FDA granted priority review to Verastem’s avutometinib (VS-6766) and defactinib (VS-6063) for the treatment of adult patients with recurrent low-grade serous ovarian cancer harboring a KRAS mutation.² A decision on the new drug application is expected in late June 2025.

REFERENCES:

1. Verastem Oncology announces US IND clearance of VS-7375, oral KRAS G12D (ON/OFF) inhibitor, enabling phase 1/2a trial in advanced solid tumors. News release. Verastem Oncology. April 24, 2025. Accessed April 24, 2025. https://tinyurl.com/3db7zt28

2. Verastem Oncology announces FDA acceptance and priority review of new drug application for avutometinib in combination with defactinib for the treatment of recurrent KRAS mutant low-grade serous ovarian cancer. News release. Verastem Oncology. December 30, 2024. Accessed April 24, 2025. https://tinyurl.com/dxsv27mu