Study of RMC-6291 in Combination with RMC-6236 in Participants with Advanced KRAS G12C Mutant Solid Tumors

NCT ID: NCT06128551

Last Updated: 2025-03-27

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

210 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-14

Study Completion Date

2026-11-30

Brief Summary

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This study is to evaluate the safety, tolerability, and PK profiles of RMC-6291 and RMC-6236 in adults with KRAS G12C-mutated solid tumors.

Detailed Description

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This is an open-label, multicenter, Phase 1b study of RMC-6291 in combination with RMC-6236 in participants with advanced KRAS G12C-mutated solid tumors, to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose and schedule (RP2DS) and provide a preliminary assessment of the antitumor activity of RMC-6291 in participants with KRASG12C tumors.

The study consists of two parts: Part 1 - Dose-Escalation and Part 2 Dose-Expansion.

Conditions

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Non-Small Cell Lung Cancer (NSCLC) Colorectal Cancer Pancreatic Ductal Adenocarcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

None (Open Label)

Study Groups

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RMC-6291 and RMC-6236

Dose escalation and Dose expansion

Group Type EXPERIMENTAL

Assigned interventions

Intervention Type DRUG

Drug: RMC-6291 and RMC-6236 Oral tablets

Interventions

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Assigned interventions

Drug: RMC-6291 and RMC-6236 Oral tablets

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 18 years of age
* Histology: pathologically documented, KRAS G12C-mutated, advanced or metastatic solid tumors not amendable to curative therapy

1. Part 1. Dose Escalation: solid tumors, previously treated
2. Part 2. Dose Expansion:

i. NSCLC, previously treated with immunotherapy, chemotherapy, and KRAS G12C (OFF) inhibitors, ii. NSCLC, previously treated with immunotherapy and chemotherapy, naïve to KRAS G12C (OFF) inhibitors, iii. NSCLC, previously treated with immunotherapy, chemotherapy, with untreated, asymptomatic central nervous system (CNS) metastases \<2 cm in size iv. Solid tumors, previously treated, naïve to KRAS G12C (OFF) inhibitors.
* ECOG performance status 0 or 1
* Adequate organ function

Exclusion Criteria

* Primary central nervous system (CNS) tumors
* Active brain metastases
* Known impairment of GI function that would alter the absorption
* Major surgical procedures within 28 days or non-study related minor procedures within 7 days of treatment
Minimum Eligible Age

18 Years

Maximum Eligible Age

125 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

Principal Investigators

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Revolution Medicines, Inc.

Role: STUDY_DIRECTOR

Revolution Medicines, Inc.

Locations

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City of Hope

Duarte, California, United States

Site Status RECRUITING

UC IRVINE Health

Orange, California, United States

Site Status RECRUITING

UC Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status RECRUITING

Stanford Cancer Institute

Stanford, California, United States

Site Status RECRUITING

University of Colorado Cancer Center

Aurora, Colorado, United States

Site Status RECRUITING

Florida Cancer Specialists

Sarasota, Florida, United States

Site Status RECRUITING

Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Site Status RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Henry Ford Cancer

Detroit, Michigan, United States

Site Status RECRUITING

START Midwest

Grand Rapids, Michigan, United States

Site Status RECRUITING

Columbia University

New York, New York, United States

Site Status RECRUITING

NYU Langone Health

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

University of Oklahoma

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

Sarah Cannon Research Institue

Nashville, Tennessee, United States

Site Status RECRUITING

Mary Crowley Cancer Research

Dallas, Texas, United States

Site Status RECRUITING

MD Anderson

Houston, Texas, United States

Site Status RECRUITING

NEXT Dallas

Irving, Texas, United States

Site Status RECRUITING

NEXT Oncology San Antonio

San Antonio, Texas, United States

Site Status RECRUITING

START Texas

San Antonio, Texas, United States

Site Status RECRUITING

NEXT Oncology Virginia

Fairfax, Virginia, United States

Site Status RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status NOT_YET_RECRUITING

West Cancer Institute

Angers, , France

Site Status RECRUITING

Institut Bergonie

Bordeaux, , France

Site Status RECRUITING

Hospital Louise Pradel

Bron, , France

Site Status RECRUITING

Oscar Lambret Center of Lillle

Lille, , France

Site Status RECRUITING

Centre Leon Berard

Lyon, , France

Site Status RECRUITING

Cancer Institute of Montpellier

Montpellier, , France

Site Status RECRUITING

CHU Nantes

Nantes, , France

Site Status RECRUITING

Institute of Cancer of Strasbourg

Strasbourg, , France

Site Status RECRUITING

Universitäts Klinikum Köln

Cologne, , Germany

Site Status RECRUITING

Klinikum Esslingen GmbH

Esslingen am Neckar, , Germany

Site Status RECRUITING

Krankenhaus Bethanien Moers

Moers, , Germany

Site Status RECRUITING

Klinkum Nurnberg Paracelsus Medical Unviersity

Nuremberg, , Germany

Site Status RECRUITING

Department of Medical Oncology - Azienda Ospedaliero Uniersitaria delle Marche

Ancona, , Italy

Site Status RECRUITING

Centro Di Riferimento Oncologico

Aviano, , Italy

Site Status RECRUITING

Institute Romagnolo per lo Studio Tumori

Meldola, , Italy

Site Status RECRUITING

Niguarda Cancer Center

Milan, , Italy

Site Status RECRUITING

Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale"

Napoli, , Italy

Site Status RECRUITING

San Luigi Hospital

Orbassano, , Italy

Site Status RECRUITING

AUSL Romagna - S.M. delle Croci Hospital

Ravenna, , Italy

Site Status RECRUITING

Netherlands Cancer Institute Antoni van Leeuwenhoek

Amsterdam, , Netherlands

Site Status RECRUITING

Pan American Center for Oncology Trials

San Juan, Puerto Rico, Puerto Rico

Site Status RECRUITING

START Barcelona - Hospital HM Nou Delfos

Barcelona, , Spain

Site Status RECRUITING

Institut Catala d'Oncologia Hospital

Barcelona, , Spain

Site Status RECRUITING

University Clinic of Navarra

Madrid, , Spain

Site Status RECRUITING

Fundacion MD Anderson Cancer Center

Madrid, , Spain

Site Status RECRUITING

START Madrid

Madrid, , Spain

Site Status RECRUITING

Hosptial Universitario 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

NEXT Oncology - Quirónsalud Madrid University Hospital

Madrid, , Spain

Site Status RECRUITING

University Clinic of Navarra

Pamplona, , Spain

Site Status RECRUITING

Hosptial Universitario Virgen Macarena

Seville, , Spain

Site Status RECRUITING

La Fe University and Polytechnic Hospital

Valencia, , Spain

Site Status RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Site Status RECRUITING

Countries

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United States France Germany Italy Netherlands Puerto Rico Spain

Central Contacts

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Revolution Medicines, Inc.

Role: CONTACT

1-844-2-REVMED

References

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Cregg J, Edwards AV, Chang S, Lee BJ, Knox JE, Tomlinson ACA, Marquez A, Liu Y, Freilich R, Aay N, Wang Y, Jiang L, Jiang J, Wang Z, Flagella M, Wildes D, Smith JAM, Singh M, Wang Z, Gill AL, Koltun ES. Discovery of Daraxonrasib (RMC-6236), a Potent and Orally Bioavailable RAS(ON) Multi-selective, Noncovalent Tri-complex Inhibitor for the Treatment of Patients with Multiple RAS-Addicted Cancers. J Med Chem. 2025 Mar 27;68(6):6064-6083. doi: 10.1021/acs.jmedchem.4c02314. Epub 2025 Mar 8.

Reference Type DERIVED
PMID: 40056080 (View on PubMed)

Other Identifiers

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RMC-6291-101

Identifier Type: -

Identifier Source: org_study_id

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