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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 : December 27, 2022
Sponsor:
Information provided by (Responsible Party):
Revolution Medicines, Inc.

Tracking Information
First Submitted Date  ICMJE May 13, 2022
First Posted Date  ICMJE May 18, 2022
Last Update Posted Date December 27, 2022
Actual Study Start Date  ICMJE May 31, 2022
Estimated Primary Completion Date June 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 28, 2022)
  • 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 ]
  • Number of Participants with Dose-Limiting Toxicity (DLT) [ Time Frame: 21 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 13, 2022)
  • Incidence and severity of treatment-emergent AEs and serious AEs, including incidence and severity of findings in laboratory values and vital signs [ Time Frame: up to 2.5 years ]
  • Number of Participants with Dose-Limiting Toxicity (DLT) [ Time Frame: 21 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2022)
  • Maximum Observed Blood Concentration (Cmax) of RMC-6236 [ Time Frame: up to 15 weeks ]
  • Time to Reach Maximum Blood Concentration (Tmax) of RMC-6236 [ Time Frame: up to 15 weeks ]
  • Area Under Blood Concentration Time Curve (AUC) of RMC-6236 [ Time Frame: up to 15 weeks ]
  • Elimination Half-Life of RMC-6236 (t1/2) [ Time Frame: 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 ]
  • Overall Response Rate (ORR) [ Time Frame: up to 2.5 years ]
    Overall response rate per RECIST v1.1
  • Duration of Response (DOR) [ Time Frame: up to 2.5 years ]
    Duration of response per RECIST v1.1
  • Disease Control Rate (DCR) [ Time Frame: up to 2.5 years ]
    Disease control rate per RECIST v1.1
  • Time to Response (TTR) [ Time Frame: up to 2.5 years ]
    Time to response per RECIST v1.1
  • Progression-Free Survival (PFS) [ Time Frame: up to 2.5 years ]
    Progression-free survival per RECIST v1.1
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of RMC-6236 in Subjects With Advanced Solid Tumors Harboring Specific Mutations in KRAS
Official Title  ICMJE Phase 1/1b Multicenter Open-Label Study of RMC-6236 in Subjects With Advanced Solid Tumors Harboring Specific Mutations in KRAS
Brief Summary Evaluate the safety and tolerability of RMC-6236 in adults with KRAS p.G12 mutant advanced solid tumors, KRAS p.G12C excluded.
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 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-small Cell Lung Cancer (NSCLC)
  • Colorectal Cancer (CRC)
  • Pancreatic Ductal Adenocarcinoma (PDAC)
  • Advanced Solid Tumors
Intervention  ICMJE Drug: RMC-6236
Oral Tablets
Study Arms  ICMJE 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).

Intervention: Drug: RMC-6236
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 13, 2022)		 141
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2025
Estimated Primary Completion Date June 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Revolution Medicines, Inc. (650) 779-2300 rmc-6236_ct-inquiry@revmed.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05379985
Other Study ID Numbers  ICMJE RMC-6236-001
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Revolution Medicines, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Revolution Medicines, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Revolution Medicines, Inc. Revolution Medicines, Inc.
PRS Account Revolution Medicines, Inc.
Verification Date December 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP