VS-7375 for adults with KRAS G12D-mutated advanced solid tumors.
A Phase 1/2, Open-label Study of VS-7375, a KRAS G12D (ON/OFF) Inhibitor, as Monotherapy and in Combination, in Patients With Advanced KRAS G12D-Mutated Solid Tumors
This trial tests VS-7375, alone and combined with other cancer drugs, in adults with unresectable or metastatic solid tumors that have the KRAS G12D mutation.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 295 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Verastem, Inc. Industry-sponsored |
| Drugs / interventions | chemotherapy, immunotherapy, radiation |
| Locations | 14 sites (Los Angeles, California and 13 other locations) |
| Trial ID | NCT07020221 on ClinicalTrials.gov |
What this trial studies
This is a Phase 1/2, multicenter, dose-escalation and expansion trial of VS-7375 given alone and in combination with several standard therapies in patients whose tumors harbor the KRAS G12D mutation. Phase 1 will define safety, tolerability, and recommended doses, while Phase 2 will explore anti-tumor activity in specific tumor cohorts such as pancreatic, colorectal, and non–small cell lung cancers. Key eligibility includes adults with measurable, advanced or metastatic disease, ECOG 0–1, and adequate organ and cardiac function. The trial is being conducted at multiple academic centers in the United States and includes endpoints for safety and objective response by RECIST v1.1.
Who should consider this trial
Good fit: Adults (≥18) with locally advanced unresectable or metastatic solid tumors confirmed to carry a KRAS G12D mutation, measurable disease, ECOG 0–1, and adequate organ and cardiac function are the intended participants.
Not a fit: Patients without the KRAS G12D mutation, with poor performance status, inadequate organ function, or who cannot meet required treatment washout periods or recovery from recent procedures likely will not benefit from this study.
Why it matters
Potential benefit: If successful, VS-7375 could provide a targeted treatment option that shrinks tumors or prolongs disease control for patients with KRAS G12D-mutant cancers who currently have few targeted therapies.
How similar studies have performed: Targeting KRAS G12D is a relatively new approach with limited clinical precedent—while KRAS G12C inhibitors have shown success, effective G12D-directed therapies remain largely unproven in humans.
Eligibility criteria
Show full inclusion / exclusion criteria
Key Inclusion Criteria: * Individuals ≥18 years of age. * Agreement to sign and date an informed consent form (ICF) approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC). * Histologic or cytologic evidence of locally advanced unresectable or metastatic solid tumor harboring a KRAS G12D mutation. * Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Adequate organ function * Adequate cardiac function * Recovered from all AEs due to previous therapies to Grade ≤1 or baseline. * Agreement to use highly effective contraception Key Exclusion Criteria: * Underwent major surgical procedure as defined by the Investigator, other than for diagnosis, within 4 weeks prior to Cycle 1 Day 1, * Receipt of chemotherapy, targeted therapy, or radiotherapy (excluding palliative radiation) within 4 weeks or 5 half-lives, whichever is shorter, or immunotherapy within 4 weeks prior to Cycle 1 Day 1 * Treatment with any investigational drug at least 4 weeks or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1. * History of treatment with direct and specific KRAS G12D inhibitors. * Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases. * Inability to swallow oral medications. * Evidence or history of uncontrolled, clinically significant hematological, renal, hepatic, endocrine, pulmonary, gastrointestinal, cardiovascular, psychiatric, coagulation, neurologic, dermatologic, autoimmune, or allergic disease * Individuals who are pregnant or breastfeeding.
Where this trial is running
Los Angeles, California and 13 other locations
- Cedars-Sinai Medical Center — Los Angeles, California, United States (Recruiting)
- Johns Hopkins University — Baltimore, Maryland, United States (Recruiting)
- Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)
- University of Michigan — Ann Arbor, Michigan, United States (Recruiting)
- Washington University School of Medicine — St Louis, Missouri, United States (Recruiting)
- Laura & Isaac Perlmutter Cancer Center at NYU Langone — New York, New York, United States (Recruiting)
- Univ of Pennsylvania, Abramson Cancer Center — Philadelphia, Pennsylvania, United States (Recruiting)
- SCRI Oncology Partners — Nashville, Tennessee, United States (Recruiting)
- MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
- Huntsman Cancer Institute — Salt Lake City, Utah, United States (Recruiting)
- University of Virginia — Charlottesville, Virginia, United States (Recruiting)
- Virginia Cancer Specialists — Fairfax, Virginia, United States (Recruiting)
- Virginia Mason Medical Center — Seattle, Washington, United States (Recruiting)
- Peninsula and Southeast Oncology — Frankston, Victoria, Australia (Recruiting)
Study contacts
- Study coordinator: Verastem Call Center
- Email: clinicaltrials@verastem.com
- Phone: 1 781 292 4204
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.