Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS

NCT ID: NCT05379985

Last Updated: 2025-11-12

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

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

754 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-31

Study Completion Date

2027-07-26

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Evaluate the safety and tolerability of RMC-6236 in adults with specific RAS mutant advanced solid tumors.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This is a Phase 1/2, multicenter open-label study to evaluate the safety, tolerability, pharmacokinetics (PK), and clinical activity of escalating doses of RMC-6236 in adult patients with advanced solid tumors harboring specific RAS mutations, and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose \[RP2D\] within investigated patient population groups. RMC-6236 is a potent, orally bioavailable RAS-MULTI(ON) inhibitor, selective for the active RAS(ON) form of both wild type and mutant variants of the canonical RAS isoforms (HRAS, NRAS, and KRAS).

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

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

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

KRAS Non-small Cell Lung Cancer Lung Cancer Colorectal Cancer Colon Cancer Metastatic Cancer Pancreatic Cancer Pancreatic Ductal Adenocarcinoma NSCLC CRC PDAC Pancreatic Neoplasms Carcinoma, Pancreatic Ductal Colorectal Neoplasms Colonic Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Lung Neoplasms Carcinoma, Non-Small-Cell Lung Neoplastic Processes Thoracic Neoplasms Antineoplastic Agents Melanoma Gynecological Cancers RAS

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Experimental: RMC-6236

Enrollment into dose exploration may be from any advanced solid tumor type with KRAS p.G12 mutations.

Enrollment into dose expansion/optimization may be from groups consisting of patients with a single histotype/genotype (for example, KRAS G12-mutated NSCLC, PDAC, CRC, RAS mutant NSCLC, Melanoma, gynecological cancer or other solid tumors not previously specified).

RAS mutant is defined as any nonsynonymous mutation of KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61)

Group Type EXPERIMENTAL

RMC-6236

Intervention Type DRUG

Oral Tablets

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

RMC-6236

Oral Tablets

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Histologically confirmed advanced solid tumor with specific KRAS G12 mutations (dose escalation) or RAS mutations (dose optimization/expansion) identified through deoxyribonucleic acid (DNA) sequencing. PDAC with wild-type RAS (expansion).
* Treatment naive or have received prior standard therapy appropriate for tumor type and stage
* Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate organ function

Exclusion Criteria

* Primary central nervous system (CNS) tumors
* Active, untreated brain metastases
* Known or suspected impairment of gastrointestinal function that may prohibit ability to swallow or absorb an oral medication
* History of any other unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol prior/concomitant therapy
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Revolution Medicines, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Revolution Medicines, Inc.

Role: STUDY_DIRECTOR

Revolution Medicines, Inc.

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

UC Irvine/Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status RECRUITING

UCLA

Santa Monica, California, United States

Site Status RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

Site Status RECRUITING

Johns Hopkins University

Baltimore, Maryland, United States

Site Status RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Perlmutter Cancer Center at 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

Columbia University

New York, New York, United States

Site Status RECRUITING

Christ Hospital Cancer Center

Cincinnati, Ohio, United States

Site Status RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status RECRUITING

University of Texas at Austin

Austin, Texas, United States

Site Status RECRUITING

Mary Crowley Cancer Research

Dallas, Texas, United States

Site Status RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Next Oncology

San Antonio, Texas, United States

Site Status RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status RECRUITING

Next Oncology Virginia

Fairfax, Virginia, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Revolution Medicines, Inc.

Role: CONTACT

Phone: 1-844-273-8633

Email: [email protected]

References

Explore related publications, articles, or registry entries linked to this study.

Jiang J, Jiang L, Maldonato BJ, Wang Y, Holderfield M, Aronchik I, Winters IP, Salman Z, Blaj C, Menard M, Brodbeck J, Chen Z, Wei X, Rosen MJ, Gindin Y, Lee BJ, Evans JW, Chang S, Wang Z, Seamon KJ, Parsons D, Cregg J, Marquez A, Tomlinson ACA, Yano JK, Knox JE, Quintana E, Aguirre AJ, Arbour KC, Reed A, Gustafson WC, Gill AL, Koltun ES, Wildes D, Smith JAM, Wang Z, Singh M. Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers. Cancer Discov. 2024 Jun 3;14(6):994-1017. doi: 10.1158/2159-8290.CD-24-0027.

Reference Type DERIVED
PMID: 38593348 (View on PubMed)

Holderfield M, Lee BJ, Jiang J, Tomlinson A, Seamon KJ, Mira A, Patrucco E, Goodhart G, Dilly J, Gindin Y, Dinglasan N, Wang Y, Lai LP, Cai S, Jiang L, Nasholm N, Shifrin N, Blaj C, Shah H, Evans JW, Montazer N, Lai O, Shi J, Ahler E, Quintana E, Chang S, Salvador A, Marquez A, Cregg J, Liu Y, Milin A, Chen A, Ziv TB, Parsons D, Knox JE, Klomp JE, Roth J, Rees M, Ronan M, Cuevas-Navarro A, Hu F, Lito P, Santamaria D, Aguirre AJ, Waters AM, Der CJ, Ambrogio C, Wang Z, Gill AL, Koltun ES, Smith JAM, Wildes D, Singh M. Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy. Nature. 2024 May;629(8013):919-926. doi: 10.1038/s41586-024-07205-6. Epub 2024 Apr 8.

Reference Type DERIVED
PMID: 38589574 (View on PubMed)

Schulze CJ, Seamon KJ, Zhao Y, Yang YC, Cregg J, Kim D, Tomlinson A, Choy TJ, Wang Z, Sang B, Pourfarjam Y, Lucas J, Cuevas-Navarro A, Ayala-Santos C, Vides A, Li C, Marquez A, Zhong M, Vemulapalli V, Weller C, Gould A, Whalen DM, Salvador A, Milin A, Saldajeno-Concar M, Dinglasan N, Chen A, Evans J, Knox JE, Koltun ES, Singh M, Nichols R, Wildes D, Gill AL, Smith JAM, Lito P. Chemical remodeling of a cellular chaperone to target the active state of mutant KRAS. Science. 2023 Aug 18;381(6659):794-799. doi: 10.1126/science.adg9652. Epub 2023 Aug 17.

Reference Type DERIVED
PMID: 37590355 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

RMC-6236-001

Identifier Type: -

Identifier Source: org_study_id