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

NCT05379985 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: RMC-6236-001
• Study Type: interventional
• Target: 754
• Locations: 1 country
• Sites: 16

Brief Summary

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

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs, including incidence and severity of findings in laboratory values and vital signs

  up to 2.5 years

• Number of Participants with Dose-Limiting Toxicity (DLT)

  21 days

Secondary Outcomes (10)

• Maximum Observed Blood Concentration (Cmax) of RMC-6236

  up to 15 weeks

• Time to Reach Maximum Blood Concentration (Tmax) of RMC-6236

  up to 15 weeks

• Area Under Blood Concentration Time Curve (AUC) of RMC-6236

  up to 15 weeks

• Elimination Half-Life of RMC-6236 (t1/2)

  up to 15 weeks

• Ratio of accumulation of RMC-6236 from a single dose to steady state with repeated dosing

  up to 15 weeks

Study Arms (1)

Experimental: RMC-6236

EXPERIMENTAL

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)

Drug: RMC-6236

Interventions

RMC-6236 DRUG

Oral Tablets

Experimental: RMC-6236

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Revolution Medicines, Inc.: lead

Study Sites (16)

UC Irvine/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

RECRUITING

UCLA

Santa Monica, California, 90404, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21287, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

RECRUITING

Columbia University

New York, New York, 10032, United States

RECRUITING

Christ Hospital Cancer Center

Cincinnati, Ohio, 45219, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

University of Texas at Austin

Austin, Texas, 78712, United States

RECRUITING

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Next Oncology

San Antonio, Texas, 78229, United States

RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

Next Oncology Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Related Publications (3)

• 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. Erratum In: Cancer Discov. 2025 Oct 6;15(10):2186. doi: 10.1158/2159-8290.CD-25-1519.

  PMID: 38593348 DERIVED

• 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.

  PMID: 38589574 DERIVED

• 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.

  PMID: 37590355 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Lung Neoplasms; Colonic Neoplasms; Neoplasm Metastasis; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Intestinal Neoplasms; Gastrointestinal Neoplasms; Neoplastic Processes; Thoracic Neoplasms; Melanoma

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Carcinoma, Ductal; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Ductal, Lobular, and Medullary; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Revolution Medicines, Inc.

  Revolution Medicines, Inc.

  STUDY DIRECTOR

Central Study Contacts

Revolution Medicines, Inc.

CONTACT

1-844-273-8633; medinfo@revmed.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2022
• First Posted: May 18, 2022
• Study Start: May 31, 2022
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): July 26, 2027
• Last Updated: November 12, 2025

Record last verified: 2025-11

Locations

US (16)