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

Primary Purpose

Non-small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC)

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RMC-6236
Sponsored by
Revolution Medicines, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer (NSCLC) focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UC Irvine/Chao Family Comprehensive Cancer CenterRecruiting
  • Dana Farber Cancer InstituteRecruiting
  • Perlmutter Cancer Center at NYU Langone HealthRecruiting
  • Memorial Sloan-Kettering Cancer CenterRecruiting
  • Columbia UniversityRecruiting
  • Christ Hospital Cancer CenterRecruiting
  • Sarah Cannon Research InstituteRecruiting
  • University of Texas at AustinRecruiting
  • Mary Crowley Cancer ResearchRecruiting
  • The University of Texas MD Anderson Cancer CenterRecruiting
  • Next OncologyRecruiting
  • Huntsman Cancer InstituteRecruiting
  • Next Oncology VirginiaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental: RMC-6236

Arm Description

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)

Outcomes

Primary Outcome Measures

Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs, including incidence and severity of findings in laboratory values and vital signs
Number of Participants with Dose-Limiting Toxicity (DLT)

Secondary Outcome Measures

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

Full Information

First Posted
May 13, 2022
Last Updated
October 23, 2023
Sponsor
Revolution Medicines, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05379985
Brief Title
Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS
Official Title
A Multicenter Open-Label Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 31, 2022 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Revolution Medicines, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
474 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental: RMC-6236
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
RMC-6236
Intervention Description
Oral Tablets
Primary Outcome Measure Information:
Title
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
Title
Number of Participants with Dose-Limiting Toxicity (DLT)
Time Frame
21 days
Secondary Outcome Measure Information:
Title
Maximum Observed Blood Concentration (Cmax) of RMC-6236
Time Frame
up to 15 weeks
Title
Time to Reach Maximum Blood Concentration (Tmax) of RMC-6236
Time Frame
up to 15 weeks
Title
Area Under Blood Concentration Time Curve (AUC) of RMC-6236
Time Frame
up to 15 weeks
Title
Elimination Half-Life of RMC-6236 (t1/2)
Time Frame
up to 15 weeks
Title
Ratio of accumulation of RMC-6236 from a single dose to steady state with repeated dosing
Time Frame
up to 15 weeks
Title
Overall Response Rate (ORR)
Description
Overall response rate per RECIST v1.1
Time Frame
up to 2.5 years
Title
Duration of Response (DOR)
Description
Duration of response per RECIST v1.1
Time Frame
up to 2.5 years
Title
Disease Control Rate (DCR)
Description
Disease control rate per RECIST v1.1
Time Frame
up to 2.5 years
Title
Time to Response (TTR)
Description
Time to response per RECIST v1.1
Time Frame
up to 2.5 years
Title
Progression-Free Survival (PFS)
Description
Progression-free survival per RECIST v1.1
Time Frame
up to 2.5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Revolution Medicines, Inc.
Phone
(650) 779-2300
Email
rmc-6236_ct-inquiry@revmed.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Revolution Medicines, Inc.
Organizational Affiliation
Revolution Medicines, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
UC Irvine/Chao Family Comprehensive Cancer Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Recruiting
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Name
Perlmutter Cancer Center at NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Individual Site Status
Recruiting
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Name
Christ Hospital Cancer Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Individual Site Status
Recruiting
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Texas at Austin
City
Austin
State/Province
Texas
ZIP/Postal Code
78712
Country
United States
Individual Site Status
Recruiting
Facility Name
Mary Crowley Cancer Research
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Individual Site Status
Recruiting
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
Next Oncology
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Individual Site Status
Recruiting
Facility Name
Next Oncology Virginia
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

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

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