FDA OKs Investigational New Drug Application for VS-7375 in Solid Tumors

The FDA has cleared the investigational new drug application of VS-7375 for clinical evaluation in advanced solid tumors including pancreatic cancer, colorectal cancer and non-small cell lung cancer.

The U.S. Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application of VS-7375, an oral KRAS G12D (ON/OFF) inhibitor for clinical evaluation in advanced solid tumors including pancreatic cancer, colorectal cancer and non-small cell lung cancer, according to a news release from Verastem Oncology.

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

The company announced that an abstract from its partner GenFleet Therapeutics has been accepted for a rapid oral presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 30 to June 3 in Chicago. The abstract highlights preliminary dose escalation results from the phase 1/2 study of VS-7375 (also known as GFH375), conducted by GenFleet.

Verastem will conduct a phase 1/2a trial in the U.S., with possible global expansion, to evaluate the safety and efficacy of VS-7375 in patients with advanced KRAS G12D-mutant solid tumors.

The phase 1 portion will begin at a dose identified as effective in initial GenFleet data to help accelerate the trial. Verastem plans to escalate dosing at levels where responses were seen in GenFleet’s study.

The phase 2a portion will assess VS-7375 as both a monotherapy and combination therapy in advanced solid tumors, including pancreatic, colorectal and non-small cell lung cancers.

“We believe there remains a significant opportunity to improve on the efficacy seen to date with other KRAS G12D-selective agents,” Paterson continued in the news release. “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. We look forward to our partner GenFleet’s oral presentation that will include updated safety and efficacy data from the phase 1 study at the ASCO annual meeting.”

The ASCO 2025 presentation, titled “A first-in-human phase 1/2 study of GFH375, a highly selective and potent oral KRAS G12D inhibitor in patients with KRAS G12D-mutant advanced solid tumors,” will be featured during the Rapid Oral Abstract Session on Developmental Therapeutics — Molecularly Targeted Agents and Tumor Biology. It is scheduled for June 2 from 8 to 9:30 a.m. CDT.

VS-7375 is an investigational oral KRAS G12D dual ON/OFF inhibitor being developed through a collaboration between Verastem Oncology and GenFleet Therapeutics. Described as a potential best-in-class compound, VS-7375 received clearance from the FDA for its IND application in April 2025, with a phase 1/2a trial expected to begin in the middle of 2025. In China, GenFleet’s IND application was approved in June 2024, and the first patient was dosed the following month.

According to the release, KRAS G12D accounts for 26% of all KRAS mutations, making it the most common KRAS mutation across human cancers. It is most frequently found in pancreatic cancers (37%), followed by colorectal (12.5%), endometrial (8%) and non-small cell lung cancers (5%). No therapies have been approved by the FDA that specifically target KRAS G12D mutations.

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