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

February 21, 2024 updated by: Revolution Medicines, Inc.

A Multicenter Open-Label Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase 1/1b, 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).

Study Type

Interventional

Enrollment (Estimated)

474

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Orange, California, United States, 92868
        • Recruiting
        • UC Irvine/Chao Family Comprehensive Cancer Center
      • Santa Monica, California, United States, 90404
        • Recruiting
        • UCLA
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins University
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana Farber Cancer Institute
    • New York
      • New York, New York, United States, 10021
        • Recruiting
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University
      • New York, New York, United States, 10016
        • Recruiting
        • Perlmutter Cancer Center at NYU Langone Health
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Recruiting
        • Christ Hospital Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon Research Institute
    • Texas
      • Austin, Texas, United States, 78712
        • Recruiting
        • University of Texas at Austin
      • Dallas, Texas, United States, 75230
        • Recruiting
        • Mary Crowley Cancer Research
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas Md Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • Next Oncology
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Next Oncology Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.
  • 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

Other inclusion/exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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, PDAC, CRC, 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
Oral Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs, including incidence and severity of findings in laboratory values and vital signs
Time Frame: up to 2.5 years
up to 2.5 years
Number of Participants with Dose-Limiting Toxicity (DLT)
Time Frame: 21 days
21 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Observed Blood Concentration (Cmax) of RMC-6236
Time Frame: up to 15 weeks
up to 15 weeks
Time to Reach Maximum Blood Concentration (Tmax) of RMC-6236
Time Frame: up to 15 weeks
up to 15 weeks
Area Under Blood Concentration Time Curve (AUC) of RMC-6236
Time Frame: up to 15 weeks
up to 15 weeks
Elimination Half-Life of RMC-6236 (t1/2)
Time Frame: up to 15 weeks
up to 15 weeks
Ratio of accumulation of RMC-6236 from a single dose to steady state with repeated dosing
Time Frame: up to 15 weeks
up to 15 weeks
Overall Response Rate (ORR)
Time Frame: up to 2.5 years
Overall response rate per RECIST v1.1
up to 2.5 years
Duration of Response (DOR)
Time Frame: up to 2.5 years
Duration of response per RECIST v1.1
up to 2.5 years
Disease Control Rate (DCR)
Time Frame: up to 2.5 years
Disease control rate per RECIST v1.1
up to 2.5 years
Time to Response (TTR)
Time Frame: up to 2.5 years
Time to response per RECIST v1.1
up to 2.5 years
Progression-Free Survival (PFS)
Time Frame: up to 2.5 years
Progression-free survival per RECIST v1.1
up to 2.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Revolution Medicines, Inc.

Investigators

  • Study Director: Revolution Medicines, Inc., Revolution Medicines, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 31, 2022

Primary Completion (Estimated)

June 1, 2024

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

May 13, 2022

First Submitted That Met QC Criteria

May 13, 2022

First Posted (Actual)

May 18, 2022

Study Record Updates

Last Update Posted (Estimated)

February 23, 2024

Last Update Submitted That Met QC Criteria

February 21, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RMC-6236-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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