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NCT07349537PHASE1Recruiting

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

Revolution Medicines, Inc.

Start Date

1/8/2026

Completion Date

10/1/2028

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

RMC-5127

DRUG

daraxonrasib

DRUG

cetuximab

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Conditions

Non-small Cell Lung Cancer (NSCLC)Colorectal Cancer (CRC)Pancreatic AdenocarcinomaPancreatic Ductal Adenocarcinoma (PDAC)PDACCRCNSCLCPancreatic CancerLung Cancer (NSCLC)Advanced Solid Tumors

Locations

Yale Cancer Center

New Haven, Connecticut 06511

United States

Johns Hopkins

Baltimore, Maryland 21231

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

START Midwest

Grand Rapids, Michigan 49546

United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York 10016

United States

NEXT - Dallas

Dallas, Texas 75039

United States

NEXT

San Antonio, Texas 78229

United States

START - San Antonio

San Antonio, Texas 78229

United States

NEXT - Virginia

Fairfax, Virginia 22031

United States