RMC-5127 for advanced cancers with KRAS G12V mutation
Phase 1/1b, Multicenter, Open-Label, Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant Solid Tumors
This trial will test whether the experimental drug RMC-5127, alone or with daraxonrasib or cetuximab, helps adults with advanced KRAS G12V-mutant solid tumors.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 574 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Revolution Medicines, Inc. Industry-sponsored |
| Drugs / interventions | cetuximab |
| Locations | 5 sites (Grand Rapids, Michigan and 4 other locations) |
| Trial ID | NCT07349537 on ClinicalTrials.gov |
What this trial studies
This open-label, multicenter Phase 1/1b trial enrolls adults with advanced KRAS G12V-mutant solid tumors to characterize safety, tolerability, pharmacokinetics, and preliminary antitumor activity of RMC-5127 as monotherapy and in two combination regimens. Participants are assigned to one of three arms—RMC-5127 alone, RMC-5127 plus daraxonrasib, or RMC-5127 plus cetuximab—with each arm including a dose exploration (Part 1) followed by a dose-expansion cohort (Part 2). Dose escalation will identify recommended doses and may include food-effect cohorts for the monotherapy arm, and efficacy signals will be monitored using RECIST v1.1 tumor measurements. The study collects safety labs, pharmacokinetic samples, and tumor response data across multiple U.S. sites.
Who should consider this trial
Good fit: Ideal candidates are adults with pathologically confirmed, locally advanced or metastatic solid tumors harboring the KRAS G12V mutation, ECOG 0–1, measurable disease, and prior progression or intolerance to standard treatments.
Not a fit: Patients without a KRAS G12V mutation, with primary central nervous system tumors, prior direct KRAS-targeted therapy, or poor performance status are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, RMC-5127 could provide a new targeted treatment option for patients with KRAS G12V-mutant advanced tumors who have exhausted standard therapies.
How similar studies have performed: While KRAS G12C inhibitors have shown clinical success, therapies specifically targeting KRAS G12V are novel and have limited clinical data to date.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * At least 18 years old and has provided informed consent. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Pathologically documented, locally advanced or metastatic KRAS G12V-mutated solid tumor malignancy. * Received and progressed or been intolerant to prior standard therapy (including targeted therapy) appropriate for tumor type and stage. * Measurable per RECIST v1.1 * Adequate organ function (bone marrow, liver, kidney, coagulation). * Able to take oral medications. Exclusion Criteria: * Primary central nervous system (CNS) tumors * Prior therapy with KRAS G12V inhibitor or direct RAS-targeted therapy (eg. degraders and/or inhibitors). * Any conditions that may affect the ability to take or absorb study drug. * Major surgery within 28 days prior to receiving study drug(s). * Patient is unable or unwilling to comply with protocol-required study visits or procedures.
Where this trial is running
Grand Rapids, Michigan and 4 other locations
- START Midwest — Grand Rapids, Michigan, United States (Recruiting)
- NEXT - Dallas — Dallas, Texas, United States (Recruiting)
- Next — San Antonio, Texas, United States (Recruiting)
- START - San Antonio — San Antonio, Texas, United States (Recruiting)
- NEXT - Virginia — Fairfax, Virginia, United States (Recruiting)
Study contacts
- Study coordinator: Revolution Medicines Study Director
- Email: medinfo@revmed.com
- Phone: 1-844-2-REVMED
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.