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

Advanced Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05379985
• Other study ID #: RMC-6236-001
• Status: Recruiting
• Phase: Phase 1
• Start date: May 31, 2022
• Est. completion date: December 2025

Study information

• Verified date: February 2024
• Source: Revolution Medicines, Inc.
• Contact: Revolution Medicines, Inc.
• Phone: (650) 779-2300
• Email: rmc-6236_ct-inquiry[@]revmed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 474
• Est. completion date: December 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• RMC-6236
Oral Tablets

Locations

Country	Name	City	State
United States	University of Texas at Austin	Austin	Texas
United States	Johns Hopkins University	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Christ Hospital Cancer Center	Cincinnati	Ohio
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	Next Oncology Virginia	Fairfax	Virginia
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Columbia University	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Perlmutter Cancer Center at NYU Langone Health	New York	New York
United States	UC Irvine/Chao Family Comprehensive Cancer Center	Orange	California
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Next Oncology	San Antonio	Texas
United States	UCLA	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Revolution Medicines, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs, including incidence and severity of findings in laboratory values and vital signs		up to 2.5 years
Primary	Number of Participants with Dose-Limiting Toxicity (DLT)		21 days
Secondary	Maximum Observed Blood Concentration (Cmax) of RMC-6236		up to 15 weeks
Secondary	Time to Reach Maximum Blood Concentration (Tmax) of RMC-6236		up to 15 weeks
Secondary	Area Under Blood Concentration Time Curve (AUC) of RMC-6236		up to 15 weeks
Secondary	Elimination Half-Life of RMC-6236 (t1/2)		up to 15 weeks
Secondary	Ratio of accumulation of RMC-6236 from a single dose to steady state with repeated dosing		up to 15 weeks
Secondary	Overall Response Rate (ORR)	Overall response rate per RECIST v1.1	up to 2.5 years
Secondary	Duration of Response (DOR)	Duration of response per RECIST v1.1	up to 2.5 years
Secondary	Disease Control Rate (DCR)	Disease control rate per RECIST v1.1	up to 2.5 years
Secondary	Time to Response (TTR)	Time to response per RECIST v1.1	up to 2.5 years
Secondary	Progression-Free Survival (PFS)	Progression-free survival per RECIST v1.1	up to 2.5 years