Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS
- Conditions
- Pancreatic Ductal Adenocarcinoma (PDAC)Non-small Cell Lung Cancer (NSCLC)Colorectal Cancer (CRC)Advanced Solid Tumors
- Interventions
- Registration Number
- NCT05379985
- Lead Sponsor
- Revolution Medicines, Inc.
- 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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 614
- Histologically confirmed advanced solid tumor with specific KRAS G12 mutations (dose escalation) or RAS mutations (dose optimization/expansion) identified through deoxyribonucleic acid (DNA) sequencing. PDAC with wild-type RAS (expansion).
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Experimental: RMC-6236 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, 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)
- Primary Outcome Measures
Name Time Method 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 Number of Participants with Dose-Limiting Toxicity (DLT) 21 days
- Secondary Outcome Measures
Name Time Method Time to Response (TTR) up to 2.5 years Time to response per RECIST v1.1
Maximum Observed Blood Concentration (Cmax) of RMC-6236 up to 15 weeks Time to Reach Maximum Blood Concentration (Tmax) of RMC-6236 up to 15 weeks Ratio of accumulation of RMC-6236 from a single dose to steady state with repeated dosing up to 15 weeks Area Under Blood Concentration Time Curve (AUC) of RMC-6236 up to 15 weeks Elimination Half-Life of RMC-6236 (t1/2) up to 15 weeks Duration of Response (DOR) up to 2.5 years Duration of response per RECIST v1.1
Progression-Free Survival (PFS) up to 2.5 years Progression-free survival per RECIST v1.1
Disease Control Rate (DCR) up to 2.5 years Disease control rate per RECIST v1.1
Overall Response Rate (ORR) up to 2.5 years Overall response rate per RECIST v1.1
Trial Locations
- Locations (16)
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
UC Irvine/Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
UCLA
🇺🇸Santa Monica, California, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Perlmutter Cancer Center at NYU Langone Health
🇺🇸New York, New York, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Columbia University
🇺🇸New York, New York, United States
Christ Hospital Cancer Center
🇺🇸Cincinnati, Ohio, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
University of Texas at Austin
🇺🇸Austin, Texas, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Next Oncology
🇺🇸San Antonio, Texas, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Next Oncology Virginia
🇺🇸Fairfax, Virginia, United States