Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors

Last updated: April 14, 2025
Sponsor: Revolution Medicines, Inc.
Overall Status: Active - Recruiting

Phase

1/2

Condition

Pancreatic Cancer

Colon Cancer; Rectal Cancer

Colorectal Cancer

Treatment

nab-paclitaxel

RMC-9805

mFOLFOX6 regimen

Clinical Study ID

NCT06445062
RMC-GI-102
  • Ages > 18
  • All Genders

Study Summary

The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard(s) of Care (SOC) or with novel agents.

The current subprotocols include the following:

Subprotocol A: RMC-6236 + 5-fluorouracil-based regimens

Subprotocol B: RMC-6236 + cetuximab with or without mFOLFOX6

Subprotocol C: RMC-6236 + gemcitabine + nab-paclitaxel

Subprotocol D: RMC-9805 with or without RMC-6236 + 5-fluorouracil-based regimens

Subprotocol E: RMC-9805 with or without RMC-6236 + cetuximab with or without mFOLFOX6

Subprotocol F: RMC-9805 with or without RMC-6236 + gemcitabine + nab-paclitaxel

Eligibility Criteria

Inclusion

Inclusion Criteria:

All Patients (unless otherwise noted):

  • ≥ 18 years of age

  • ECOG PS is 0 to 1

  • Adequate organ function as outlined by the study

  • Pathologically or cytologically documented pancreatic carcinoma or poorlydifferentiated pancreatic carcinoma with metastatic disease or RAS-mutated,histologically or cytologically confirmed colorectal adenocarcinoma with documentedunresectable or metastatic disease (Subprotocol A, B, and C)

  • Presence of RAS G12D mutation (Subprotocol D, E, F)

Exclusion

Exclusion Criteria:

All Patients:

  • Primary central nervous system (CNS) tumors

  • Impaired gastrointestinal (GI) function that may significantly alter the absorptionof RMC drugs

  • Major surgery within 28 days of first dose

Other inclusion/exclusion criteria may apply.

Study Design

Total Participants: 1130
Treatment Group(s): 8
Primary Treatment: nab-paclitaxel
Phase: 1/2
Study Start date:
May 24, 2024
Estimated Completion Date:
July 15, 2027

Study Description

The platform study design allows combinations of RAS(ON) inhibitors with other anticancer agents to be evaluated in patients with RAS-mutated solid tumors with a focus on GI cancers.

This is an open-label platform study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard of Care (SOC) or with novel agents, and to define the Recommended Phase 2 Dose and Schedule (RP2DS). Enrollment of patients with RAS mutations will be specified in each subprotocol.

Subprotocol A is an open-label, multicenter study of RMC-6236 in combination with 5-fluorouracil-based regimens in patients with treatment-naïve unresectable or metastatic colorectal cancer or treatment-naïve metastatic pancreatic ductal adenocarcinoma. Subprotocol B is an open-label, multicenter study of RMC-6236 in combination with cetuximab with or without mFOLFOX6 in patients with unresectable or metastatic colorectal cancer or patients with previously treated or treatment-naïve metastatic pancreatic ductal adenocarcinoma. Subprotocol C is an open-label, multicenter study of RMC-6236 in combination with gemcitabine and nab-paclitaxel in patients with treatment-naïve metastatic pancreatic ductal adenocarcinoma. Subprotocol D is an open-label, multicenter study of RMC-9805 with or without RMC-6236 in combination with 5-fluorouracil-based regimens in patients with RAS G12D-mutant unresectable or metastatic colorectal cancer or metastatic pancreatic ductal adenocarcinoma. Subprotocol E is an open-label, multicenter study of RMC-9805 with or without RMC-6236 in combination with cetuximab-based therapies with or without mFOLFOX6 in patients with RAS G12D-mutant unresectable or metastatic colorectal cancer or metastatic pancreatic ductal adenocarcinoma. Subprotocol F is an open-label, multicenter study of RMC-9805 with or without RMC-6236 in combination with gemcitabine and nab-paclitaxel in patients with RAS G12D-mutant metastatic pancreatic ductal adenocarcinoma.

Each subprotocol consists of two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion.

Connect with a study center

  • Mayo Clinic Hospital

    Phoenix, Arizona 85054
    United States

    Active - Recruiting

  • HonorHealth Research Institute

    Scottsdale, Arizona 85258
    United States

    Active - Recruiting

  • UCLA Hematology/Oncology- Santa Monica

    Los Angeles, California 90404
    United States

    Active - Recruiting

  • University of Colorado Hospital-Anschutz Cancer Pavilion

    Aurora, Colorado 88045
    United States

    Active - Recruiting

  • Mayo Clinic Cancer Center

    Jacksonville, Florida 32224
    United States

    Active - Recruiting

  • Moffitt Cancer Center

    Tampa, Florida 33612
    United States

    Active - Recruiting

  • The Sidney Kimmel Comprehensive Cancer Center at John Hopkins

    Baltimore, Maryland 21287
    United States

    Active - Recruiting

  • Dana Farber Cancer Institute

    Boston, Massachusetts 02215
    United States

    Active - Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts 02114
    United States

    Active - Recruiting

  • Mayo Clinic

    Rochester, Minnesota 55905
    United States

    Active - Recruiting

  • Columbia University Medical Center

    New York, New York 10032
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Cancer Center Main Campus

    New York, New York 10065
    United States

    Active - Recruiting

  • Duke University Medical Center

    Durham, North Carolina 27710
    United States

    Active - Recruiting

  • University of Cincinnati Medical Center

    Cincinnati, Ohio 45267
    United States

    Active - Recruiting

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania 19104
    United States

    Active - Recruiting

  • SCRI Oncology Partners

    Nashville, Tennessee 37203
    United States

    Active - Recruiting

  • Baylor College of Medicine

    Houston, Texas 77030
    United States

    Active - Recruiting

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas 77030
    United States

    Active - Recruiting

  • NEXT Oncology Dallas

    Irving, Texas 75039
    United States

    Active - Recruiting

  • Huntsman Cancer Institute, University of Utah

    Salt Lake City, Utah 84112
    United States

    Active - Recruiting

  • Virginia Cancer Specialists

    Fairfax, Virginia 22314
    United States

    Active - Recruiting

  • Fred Hutchinson Cancer Center

    Seattle, Washington 98109
    United States

    Active - Recruiting

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