Study of RMC-9805 in Participants With KRAS G12D-Mutant Solid Tumors
- Conditions
- Pancreatic Ductal Adenocarcinoma (PDAC)Non-small Cell Lung Cancer (NSCLC)Colorectal Cancer (CRC)Advanced Solid Tumors
- Interventions
- Registration Number
- NCT06040541
- Lead Sponsor
- Revolution Medicines, Inc.
- Brief Summary
This study is to evaluate the safety and tolerability of RMC-9805 as monotherapy and in combination with RMC-6236 in adults with KRAS G12D-mutant solid tumors.
- Detailed Description
This is an open-label, multicenter, Phase 1/1b study of RMC-9805, a selective and orally bioavailable KRAS G12D(ON) inhibitor, in subjects with KRASG12D-mutant solid tumors to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of two arms: RMC-9805 monotherapy arm and RMC-9805 plus RMC-6236 combination arm. Both arms consist of two parts: Part 1- dose exploration and Part 2- dose expansion.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 444
- Pathologically documented, locally advanced or metastatic solid tumor with a KRAS G12D-mutation
- Received and progressed or been intolerant to prior standard therapy (including targeted therapy) appropriate for tumor type and stage
- ECOG performance status 0 or 1
- Adequate organ function
- Primary central nervous system (CNS) tumors
- Known or suspected leptomeningeal or active brain metastases or spinal cord compression
- Known or suspected impairment of gastrointestinal function that may prohibit ability to swallow or absorb an oral medication
- Participant was previously treated with an investigational KRAS G12D inhibitor, pan- or multi-RAS inhibitor, or had prior therapy with any direct RAS-targeted therapy (eg, degraders and inhibitors)
Other inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RMC-9805 plus RMC-6236 combination arm RMC-9805 Dose exploration and dose expansion RMC-9805 plus RMC-6236 combination arm RMC-6236 Dose exploration and dose expansion RMC-9805 monotherapy arm RMC-9805 Dose exploration and dose expansion
- Primary Outcome Measures
Name Time Method Adverse events Up to 3 years Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs and clinically significant changes in laboratory values, ECGs, and vital signs
Dose Limiting Toxicities 21 days Number of participants with Dose Limiting Toxicities (DLTs)
- Secondary Outcome Measures
Name Time Method Ratio of accumulation of RMC-9805 from a single dose to steady state with repeated dosing as monotherapy and in combination with RMC-6236, and ratio of accumulation of RMC-6236 in combination with RMC-9805 up to 21 weeks accumulation ratio
Duration of Response (DOR) up to 3 years Assess per RECIST v1.1
Disease Control Rate (DCR) up to 3 years Assess per RECIST v1.1
Area Under Blood Concentration Time Curve (AUC) of RMC-9805 as monotherapy and in combination with RMC-6236, and AUC of RMC-6236 in combination with RMC-9805 up to 21 weeks AUC
Progression-Free Survival (PFS) up to 3 years Assess per RECIST v1.1
Elimination Half-Life (t1/2) of RMC-9805 as monotherapy and in combination with RMC-6236, and t1/2 of RMC-6236 in combination with RMC-9805 up to 21 weeks t1/2
Time to Response (TTR) up to 3 years Assess per RECIST v1.1
Maximum Observed Blood Concentration (Cmax) of RMC-9805 as monotherapy and in combination with RMC-6236, and Cmax of RMC-6236 in combination with RMC-9805 up to 21 weeks Cmax
Time to Reach Maximum Blood Concentration (Tmax) of RMC-9805 as monotherapy and in combination with RMC-6236, and Tmax of RMC-6236 in combination with RMC-9805 up to 21 weeks Tmax
Overall Response Rate (ORR) up to 3 years Assess per RECIST v1.1
Trial Locations
- Locations (17)
University of California, Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Smilow Cancer Hospital (Yale University)
🇺🇸New Haven, Connecticut, United States
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
NYU Langone
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Duke Cancer Center
🇺🇸Durham, North Carolina, United States
Carolina BioOncology Institute
🇺🇸Huntersville, North Carolina, United States
The Christ Hospital
🇺🇸Cincinnati, Ohio, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
University of Texas, MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
START
🇺🇸San Antonio, Texas, United States
NEXT Oncology Virginia
🇺🇸Fairfax, Virginia, United States