We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluation of RMC-6236 in Subjects With Advanced Solid Tumors Harboring Specific Mutations in KRAS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05379985
Recruitment Status : Recruiting
First Posted : May 18, 2022
Last Update Posted : September 13, 2022
Sponsor:
Information provided by (Responsible Party):
Revolution Medicines, Inc.

Brief Summary:
Evaluate the safety and tolerability of RMC-6236 in adults with KRAS p.G12 mutant advanced solid tumors, KRAS p.G12C excluded.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer (NSCLC) Colorectal Cancer (CRC) Pancreatic Ductal Adenocarcinoma (PDAC) Advanced Solid Tumors Drug: RMC-6236 Phase 1

Detailed Description:
This is a Phase 1/1b, open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetics (PK), and clinical activity of escalating doses of RMC-6236 in adult subjects with KRAS p.G12 mutant advanced solid tumors, p.G12C excluded, and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose [RP2D] within investigated subject population groups. RMC-6236 is a potent, orally bioavailable RASMUTLI(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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 141 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/1b Multicenter Open-Label Study of RMC-6236 in Subjects With Advanced Solid Tumors Harboring Specific Mutations in KRAS
Actual Study Start Date : May 31, 2022
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental: RMC-6236

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

Dose Expansion may proceed with one or more groups consisting of subjects with a single histotype/genotype (for example, KRAS p.G12 mutant NSCLC, PDAC, or CRC).

Drug: RMC-6236
Oral Tablets




Primary Outcome Measures :
  1. 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 ]
  2. Number of Participants with Dose-Limiting Toxicity (DLT) [ Time Frame: 21 days ]

Secondary Outcome Measures :
  1. Maximum Observed Blood Concentration (Cmax) of RMC-6236 [ Time Frame: up to 15 weeks ]
  2. Time to Reach Maximum Blood Concentration (Tmax) of RMC-6236 [ Time Frame: up to 15 weeks ]
  3. Area Under Blood Concentration Time Curve (AUC) of RMC-6236 [ Time Frame: up to 15 weeks ]
  4. Elimination Half-Life of RMC-6236 (t1/2) [ Time Frame: up to 15 weeks ]
  5. Ratio of accumulation of RMC-6236 from a single dose to steady state with repeated dosing [ Time Frame: up to 15 weeks ]
  6. Overall Response Rate (ORR) [ Time Frame: up to 2.5 years ]
    Overall response rate per RECIST v1.1

  7. Duration of Response (DOR) [ Time Frame: up to 2.5 years ]
    Duration of response per RECIST v1.1

  8. Disease Control Rate (DCR) [ Time Frame: up to 2.5 years ]
    Disease control rate per RECIST v1.1

  9. Time to Response (TTR) [ Time Frame: up to 2.5 years ]
    Time to response per RECIST v1.1

  10. Progression-Free Survival (PFS) [ Time Frame: up to 2.5 years ]
    Progression-free survival per RECIST v1.1



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed advanced solid tumor with KRAS p.G12A, KRAS p.G12D, KRAS p.G12R, KRAS p.G12S, or KRAS p.G12V mutations 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 to 1
  • Adequate organ function

Exclusion Criteria:

  • Tumor harboring the KRAS p.G12C mutation
  • Primary central nervous system (CNS) tumors
  • Known or suspected leptomeningeal or brain metastases or spinal cord compression
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05379985


Contacts
Layout table for location contacts
Contact: Revolution Medicines, Inc. (650) 779-2300 rmc-6236_ct-inquiry@revmed.com

Locations
Layout table for location information
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Perlmutter Cancer Center at NYU Langone Health Recruiting
New York, New York, United States, 10016
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10021
United States, Ohio
Christ Hospital Cancer Center Recruiting
Cincinnati, Ohio, United States, 45219
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Mary Crowley Cancer Research Recruiting
Dallas, Texas, United States, 75230
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Next Oncology Recruiting
San Antonio, Texas, United States, 78229
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
United States, Virginia
Next Oncology Virginia Recruiting
Fairfax, Virginia, United States, 22031
Sponsors and Collaborators
Revolution Medicines, Inc.
Investigators
Layout table for investigator information
Study Director: Revolution Medicines, Inc. Revolution Medicines, Inc.
Layout table for additonal information
Responsible Party: Revolution Medicines, Inc.
ClinicalTrials.gov Identifier: NCT05379985    
Other Study ID Numbers: RMC-6236-001
First Posted: May 18, 2022    Key Record Dates
Last Update Posted: September 13, 2022
Last Verified: June 2022

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Revolution Medicines, Inc.:
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Adenocarcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type