Study of RMC-6291 in Combination With RMC-6236 in Participants With Advanced KRAS G12C Mutant Solid Tumors
- Conditions
- Colorectal CancerPancreatic Ductal AdenocarcinomaNon-Small Cell Lung Cancer (NSCLC)
- Interventions
- Drug: Assigned interventions
- Registration Number
- NCT06128551
- Lead Sponsor
- Revolution Medicines, Inc.
- Brief Summary
This study is to evaluate the safety, tolerability, and PK profiles of RMC-6291 and RMC-6236 in adults with KRAS G12C-mutated solid tumors.
- Detailed Description
This is an open-label, multicenter, Phase 1b study of RMC-6291 in combination with RMC-6236 in participants with advanced KRAS G12C-mutated solid tumors, to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose and schedule (RP2DS) and provide a preliminary assessment of the antitumor activity of RMC-6291 in participants with KRASG12C tumors.
The study consists of two parts: Part 1 - Dose-Escalation and Part 2 Dose-Expansion.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 210
-
18 years of age
-
Histology: pathologically documented, KRAS G12C-mutated, advanced or metastatic solid tumors not amendable to curative therapy
- Part 1. Dose Escalation: solid tumors, previously treated
- Part 2. Dose Expansion:
i. NSCLC, previously treated with immunotherapy, chemotherapy, and KRAS G12C (OFF) inhibitors, ii. NSCLC, previously treated with immunotherapy and chemotherapy, naïve to KRAS G12C (OFF) inhibitors, iii. NSCLC, previously treated with immunotherapy, chemotherapy, with untreated, asymptomatic central nervous system (CNS) metastases <2 cm in size iv. Solid tumors, previously treated, naïve to KRAS G12C (OFF) inhibitors.
-
ECOG performance status 0 or 1
-
Adequate organ function
- Primary central nervous system (CNS) tumors
- Active brain metastases
- Known impairment of GI function that would alter the absorption
- Major surgical procedures within 28 days or non-study related minor procedures within 7 days of treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description RMC-6291 and RMC-6236 Assigned interventions Dose escalation 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 vitals signs
Dose Limiting Toxicities 21 days Number of participants with dose limiting toxicities
- Secondary Outcome Measures
Name Time Method Maximum Observed Blood Concentration of RMC-6291 and RMC-6236 up to 21 weeks Cmax
Elimination Half-Life of RMC-6291 and RMC-6236 up to 21 weeks t1/2
Overall Response Rate (ORR) up to 3 years Overall response rate RECIST v1.1
Progression-Free Survival (PFS) up to 3 years Progression-free survival per RECIST v1.1
Disease Control Rate up to 3 years Disease Control rate per RECIST v1.1
Time to Reach Maximum Blood Concentration of RMC-6291 and RMC-6236 up to 21 weeks Tmax
Area Under Blood Concentration Time Curve of RMC-6291 and RMC-6236 up to 21 weeks AUC
Ratio of accumulation of RMC-6291 and RMC-6236 from a single dose to steady state with repeated dosing up to 21 weeks accumulation ratio
Duration of Response (DOR) up to 3 years Duration of response per RECIST v1.1
Time to Response (TTR) up to 3 years Time to response per RECIST v1.1
Trial Locations
- Locations (53)
City of Hope
🇺🇸Duarte, California, United States
UC IRVINE Health
🇺🇸Orange, California, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
Henry Ford Cancer
🇺🇸Detroit, Michigan, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Institut Bergonie
🇫🇷Bordeaux, France
Hospital Louise Pradel
🇫🇷Bron, France
Oscar Lambret Center of Lillle
🇫🇷Lille, France
Centre Leon Berard
🇫🇷Lyon, France
CHU Nantes
🇫🇷Nantes, France
Institute of Cancer of Strasbourg
🇫🇷Strasbourg, France
Klinikum Esslingen GmbH
🇩🇪Esslingen, Germany
Krankenhaus Bethanien Moers
🇩🇪Moers, Germany
Klinkum Nurnberg Paracelsus Medical Unviersity
🇩🇪Nurnberg, Germany
Centro Di Riferimento Oncologico
🇮🇹Aviano, Italy
S.C. Oncologic Falck
🇮🇹Milano, Italy
Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale"
🇮🇹Napoli, Italy
San Luigi Hospital
🇮🇹Orbassano, Italy
Institut Catala d'Oncologia Hospital
🇪🇸Barcelona, Spain
Fundacion MD Anderson Cancer Center
🇪🇸Madrid, Spain
START Madrid
🇪🇸Madrid, Spain
Hosptial Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hosptial Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
UC Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Stanford Cancer Institute
🇺🇸Stanford, California, United States
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
START Midwest
🇺🇸Grand Rapids, Michigan, United States
Columbia University
🇺🇸New York, New York, United States
NYU Langone Health
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Sarah Cannon Research Institue
🇺🇸Nashville, Tennessee, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
MD Anderson
🇺🇸Houston, Texas, United States
NEXT Dallas
🇺🇸Irving, Texas, United States
NEXT Oncology San Antonio
🇺🇸San Antonio, Texas, United States
START Texas
🇺🇸San Antonio, Texas, United States
NEXT Oncology Virginia
🇺🇸Fairfax, Virginia, United States
West Cancer Institute
🇫🇷Angers, France
Cancer Institute of Montpellier
🇫🇷Montpellier, France
Universitäts Klinikum Köln
🇩🇪Köln, Germany
Department of Medical Oncology - Azienda Ospedaliero Uniersitaria delle Marche
🇮🇹Ancona, Italy
Institute Romagnolo per lo Studio Tumori
🇮🇹Meldola, Italy
AUSL Romagna - S.M. delle Croci Hospital
🇮🇹Ravenna, Italy
Netherlands Cancer Institute Antoni van Leeuwenhoek
🇳🇱Amsterdam, Netherlands
Pan American Center for Oncology Trials
🇵🇷San Juan, Puerto Rico
START Barcelona - Hospital HM Nou Delfos
🇪🇸Barcelona, Spain
University Clinic of Navarra
🇪🇸Pamplona, Spain
NEXT Oncology - Quirónsalud Madrid University Hospital
🇪🇸Madrid, Spain
La Fe University and Polytechnic Hospital
🇪🇸Valencia, Spain