RecruitingInterventionalPhase 1

Phase 1/1b, Multicenter, Open-Label, Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant Solid Tumors

NCT ID: NCT07349537Sponsor: Revolution Medicines, Inc.Last updated: 2026-06-01

Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of RMC-5127 as a monotherapy and in combination with either daraxonrasib or cetuximab in adults with KRAS G12V-mutant solid tumors.

Detailed description

This is an open-label, multicenter, Phase 1/1b study of RMC-5127 in adults with advanced KRAS G12V-mutant solid tumors to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of three arms: RMC-5127 monotherapy arm, RMC-5127 plus daraxonrasib combination arm, and RMC-5127 plus cetuximab combination arm. All arms consist of two parts: Part 1- dose exploration and Part 2- dose expansion. Both parts of the monotherapy arm may include Food Effect Cohorts.

Arms & interventions

DrugRMC-5127
oral tablets
Drugdaraxonrasib
oral tablets
Drugcetuximab
IV infusion

Outcome measures

Primary

Number of patients with adverse events (AEs)
Number of patients with AEs as assessed by Common Terminology Criteria for Adverse Events CTCAE v5
Time frame: Up to approximately 3 years
Changes in vital signs
Number of patients with changes from baseline in vital signs
Time frame: Up to approximately 3 years
Changes in electrocardiogram (ECG) test values
Number of patients with changes from baseline in ECG test values
Time frame: Up to approximately 3 years
Changes in clinical laboratory test values
Number of patients with changes from baseline in clinical laboratory test values
Time frame: Up to approximately 3 years
Dose Limiting Toxicities
Number of patients with dose limiting toxicities
Time frame: Up to 28 days

Secondary

Cmax concentrations of RMC-5127 and daraxonrasib
Time frame: Up to Cycle 5 Day 1 (each cycle is up to 28 days)
Tmax concentration of RMC-5127 and daraxonrasib
Time frame: Up to Cycle 5 Day 1 (each cycle is up to 28 days)
AUC concentrations of RMC-5127 and daraxonrasib
Time frame: Up to Cycle 5 Day 1 (each cycle is up to 28 days)
Ratio of accumulation of RMC-5127
Time frame: Up to Cycle 5 Day 1 (each cycle is up to 28 days)
Half-Life of RMC-5127 and daraxonrasib
Time frame: Up to Cycle 5 Day 1 (each cycle is up to 28 days)
Objective Response Rate (ORR)
Time frame: Up to approximately 3 years
Duration of Response (DOR)
Time frame: Up to approximately 3 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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.