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

• ClinicalTrials.gov Identifier: NCT05379985
• Recruitment Status: Recruiting
• First Posted: May 18, 2022
• Last Update Posted: February 23, 2024
• Sponsor: Revolution Medicines, Inc.
• Information provided by (Responsible Party): Revolution Medicines, Inc.

Tracking Information

• First Submitted Date: May 13, 2022
• First Posted Date: May 18, 2022
• Last Update Posted Date: February 23, 2024
• Actual Study Start Date: May 31, 2022
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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 ]

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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).
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non-small Cell Lung Cancer (NSCLC)
• Colorectal Cancer (CRC)
• Pancreatic Ductal Adenocarcinoma (PDAC)
• Advanced Solid Tumors

Intervention

Drug: RMC-6236

Oral Tablets

Study Arms

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)

Intervention: Drug: RMC-6236

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 23, 2023): 474
• Original Estimated Enrollment (submitted: May 13, 2022): 141
• Estimated Study Completion Date: December 2025
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Revolution Medicines, Inc.; (650) 779-2300; rmc-6236_ct-inquiry@revmed.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05379985
• Other Study ID Numbers: 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: Not Provided
• Current Responsible Party: Revolution Medicines, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Revolution Medicines, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Revolution Medicines, Inc.
• Verification Date: February 2024