Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant Solid Tumors

May 28, 2026 updated by: Revolution Medicines, Inc.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

574

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Revolution Medicines Study Director
  • Phone Number: 1-844-2-REVMED
  • Email: medinfo@revmed.com

Study Locations

  • United States
    • Michigan
      • Grand Rapids, Michigan, United States, 49546
    • Texas
      • Dallas, Texas, United States, 75039
      • San Antonio, Texas, United States, 78229
      • San Antonio, Texas, United States, 78229
    • Virginia
      • Fairfax, Virginia, United States, 22031

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: RMC-5127 Monotherapy
Dose Escalation and Dose Expansion
Drug: RMC-5127
oral tablets
Experimental: Arm B: RMC-5127 + Daraxonrasib Combination
Dose Escalation and Dose Expansion
Drug: daraxonrasib
oral tablets
Drug: RMC-5127
oral tablets
Experimental: Arm C: RMC-5127 + Cetuximab Combination
Dose Escalation and Dose Expansion
Drug: cetuximab
IV infusion
Drug: RMC-5127
oral tablets

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cmax concentrations of RMC-5127 and daraxonrasib
Time Frame: Up to Cycle 5 Day 1 (each cycle is up to 28 days)
Maximum blood concentration (Cmax) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and Cmax of daraxonrasib in combination with RMC-5127 over time as applicable
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)
Time to reach maximum blood concentration (Tmax) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and Tmax of daraxonrasib in combination with RMC-5127 over time as applicable
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)
Area under the blood concentration time curve (AUC) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and AUC of daraxonrasib in combination with RMC-5127 over time as applicable
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)
Ratio of accumulation of RMC-5127 from a single dose to steady state with repeated dosing as monotherapy and in combination with darabxrasib or cetuximab over time as applicable
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)
Elimination Half-Life (t1/2) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and t1/2 of daraxonrasib in combination with RMC-5127 over time as applicable
Up to Cycle 5 Day 1 (each cycle is up to 28 days)
Objective Response Rate (ORR)
Time Frame: Up to approximately 3 years
ORR per response evaluation criteria in solid tumors (RECIST) v1.1
Up to approximately 3 years
Duration of Response (DOR)
Time Frame: Up to approximately 3 years
DOR per RECIST v1.1
Up to approximately 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Revolution Medicines, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 8, 2026

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

October 1, 2028

Study Registration Dates

First Submitted

January 9, 2026

First Submitted That Met QC Criteria

January 9, 2026

First Posted (Actual)

January 16, 2026

Study Record Updates

Last Update Posted (Actual)

June 1, 2026

Last Update Submitted That Met QC Criteria

May 28, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RMC-5127-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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