Verastem Oncology has begun dosing the first patient in its U.S. Phase 1/2a study of VS-7375, an oral inhibitor targeting the KRAS G12D mutation in solid tumors. The trial, known as VS-7375-101, will assess safety, tolerability and preliminary efficacy of the drug in individuals with advanced KRAS G12D-mutant cancers.
VS-7375-101 launches with a monotherapy dose-escalation phase starting at 400mg, a dose informed by earlier work in China by Verastem’s partner, GenFleet Therapeutics. At the 2025 ASCO Annual Meeting, GenFleet reported favorable initial safety and signs of tumor response in its dose-escalation segment of the GFH375 study, as the compound is called in China.
Once the optimal monotherapy dose is identified, Verastem plans to expand cohorts of patients with metastatic pancreatic cancer and non-small cell lung cancer. A parallel arm will explore VS-7375 in combination with cetuximab, with further expansion in colorectal cancer contingent on safety and early activity.
In a statement, Verastem CEO Dan Paterson highlighted the trial’s launch as a key step following the company’s recent FDA approvals and trial advances in pancreatic cancer. Dr. John Hayslip, Verastem’s chief medical officer, noted that VS-7375’s design, intended to bind KRAS in both its active and inactive states, may build on the antitumor effects seen so far with other selective agents.
KRAS G12D is the most common single KRAS mutation, found in roughly one-quarter of all KRAS-mutated cancers, and particularly prevalent in pancreatic (37%), colorectal (12.5%), endometrial (8%) and non-small cell lung (5%) tumors. To date, no FDA-approved treatments specifically address this mutation.
Verastem and GenFleet’s collaboration on VS-7375 began with GenFleet’s IND clearance in China in June 2024 and Verastem’s U.S. IND approval in April 2025. The U.S. study will initially enroll patients at sites across the country, with plans to open additional centers internationally.
Key Trial Details
- Study: VS-7375-101, Phase 1/2a monotherapy and combination study
- Drug: VS-7375, oral KRAS G12D dual-state inhibitor
- Population: Adults with advanced KRAS G12D-mutant solid tumors
- Dose Escalation: Starting at 400 mg once daily
- Expansion Cohorts: Pancreatic cancer, non-small cell lung cancer; colorectal cancer in combination with cetuximab