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

NCT ID: NCT07349537

Last Updated: 2026-02-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

574 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-08

Study Completion Date

2028-10-31

Brief Summary

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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

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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.

Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: RMC-5127 Monotherapy

Dose Escalation and Dose Expansion

Group Type EXPERIMENTAL

RMC-5127

Intervention Type DRUG

oral tablets

Arm B: RMC-5127 + Daraxonrasib Combination

Dose Escalation and Dose Expansion

Group Type EXPERIMENTAL

RMC-5127

Intervention Type DRUG

oral tablets

daraxonrasib

Intervention Type DRUG

oral tablets

Arm C: RMC-5127 + Cetuximab Combination

Dose Escalation and Dose Expansion

Group Type EXPERIMENTAL

RMC-5127

Intervention Type DRUG

oral tablets

cetuximab

Intervention Type DRUG

IV infusion

Interventions

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RMC-5127

oral tablets

Intervention Type DRUG

daraxonrasib

oral tablets

Intervention Type DRUG

cetuximab

IV infusion

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Revolution Medicines, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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START Midwest

Grand Rapids, Michigan, United States

Site Status RECRUITING

NEXT - Dallas

Dallas, Texas, United States

Site Status RECRUITING

NEXT

San Antonio, Texas, United States

Site Status RECRUITING

START - San Antonio

San Antonio, Texas, United States

Site Status RECRUITING

NEXT - Virginia

Fairfax, Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Revolution Medicines Study Director

Role: CONTACT

1-844-2-REVMED

Facility Contacts

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Olivia Sweeney

Role: primary

616-954-6674

NEXT TXReferrels

Role: primary

972-893-8800

Jordan Georg

Role: primary

210-580-9521

Isabel Jimenez

Role: primary

210-593-5265

Paolo Umayam

Role: primary

703-783-4546

Other Identifiers

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RMC-5127-001

Identifier Type: -

Identifier Source: org_study_id

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