Phase 3 Study of Daraxonrasib (RMC-6236) in Patients With Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)
- Conditions
- Pancreatic CancerPDACPDAC - Pancreatic Ductal Adenocarcinoma
- Interventions
- Registration Number
- NCT06625320
- Lead Sponsor
- Revolution Medicines, Inc.
- Brief Summary
The purpose of this study is to evaluate the safety and efficacy of a novel RAS(ON) inhibitor compared to standard(s) of care (SOC) treatment.
- Detailed Description
This is a global, randomized, open-label, Phase 3 study designed to evaluate whether treatment with RMC-6236 will improve progression free survival (PFS) or overall survival (OS) compared to Investigator's choice of standard of care chemotherapy in patients with metastatic PDAC who were previously treated with one prior line of therapy with 5-fluorouracil (5-FU) based or gemcitabine-based regimen.
Patients will be randomized in a 1:1 ratio to receive RMC-6236 (Arm A) or Investigator's choice of standard of care chemotherapy (Arm B).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 460
- At least 18 years old and has provided informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Histologically or cytologically confirmed PDAC with metastatic disease.
- Measurable disease per RECIST 1.1.
- Adequate organ function (bone marrow, liver, kidney, coagulation)
- Documented RAS mutation status, either mutant or wild-type. RAS mutations defined as nonsynonymous mutations in KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61).
- Able to take oral medications.
- Prior therapy with direct RAS-targeted therapy (eg. degraders and/or inhibitors).
- History of or known central nervous system metastatic disease.
- Any conditions that may affect the ability to take or absorb study treatment
- Major surgery within 4 weeks prior to randomization.
- Patient is unable or unwilling to comply with protocol-required study visits or procedures
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RMC-6236 RMC-6236 Study drug Investigator's choice of standard of care therapy Gemcitabine Patients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments: * Gemcitabine and nab-paclitaxel (GnP) * Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX) * Liposomal irinotecan (Nal-IRI + 5-FU/LV) * Oxaliplatin, leucovorin and 5-FU IV (FOLFOX) Investigator's choice of standard of care therapy nab-paclitaxel Patients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments: * Gemcitabine and nab-paclitaxel (GnP) * Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX) * Liposomal irinotecan (Nal-IRI + 5-FU/LV) * Oxaliplatin, leucovorin and 5-FU IV (FOLFOX) Investigator's choice of standard of care therapy Irinotecan Patients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments: * Gemcitabine and nab-paclitaxel (GnP) * Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX) * Liposomal irinotecan (Nal-IRI + 5-FU/LV) * Oxaliplatin, leucovorin and 5-FU IV (FOLFOX) Investigator's choice of standard of care therapy Liposomal irinotecan Patients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments: * Gemcitabine and nab-paclitaxel (GnP) * Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX) * Liposomal irinotecan (Nal-IRI + 5-FU/LV) * Oxaliplatin, leucovorin and 5-FU IV (FOLFOX) Investigator's choice of standard of care therapy 5-fluorouracil Patients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments: * Gemcitabine and nab-paclitaxel (GnP) * Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX) * Liposomal irinotecan (Nal-IRI + 5-FU/LV) * Oxaliplatin, leucovorin and 5-FU IV (FOLFOX) Investigator's choice of standard of care therapy Oxaliplatin Patients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments: * Gemcitabine and nab-paclitaxel (GnP) * Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX) * Liposomal irinotecan (Nal-IRI + 5-FU/LV) * Oxaliplatin, leucovorin and 5-FU IV (FOLFOX) Investigator's choice of standard of care therapy leucovorin Patients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments: * Gemcitabine and nab-paclitaxel (GnP) * Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX) * Liposomal irinotecan (Nal-IRI + 5-FU/LV) * Oxaliplatin, leucovorin and 5-FU IV (FOLFOX)
- Primary Outcome Measures
Name Time Method Progression free survival (PFS) in the RAS G12-mutant population Up to approximately 3 years PFS is defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is per response evaluation criteria in solid tumors (RECIST) v1.1 and as assessed by blinded independent central review (BICR)
Overall survival (OS) in the RAS G12-mutant population Up to approximately 3 years OS is defined as the time from randomization until death from any cause.
- Secondary Outcome Measures
Name Time Method PFS in the all-patient population Up to approximately 3 years PFS is defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is per RECIST v1.1 and as assessed by BICR.
Objective response in the RAS G12 and all-patient populations Up to approximately 3 years Objective response is defined as partial response (PR) or completed response (CR) per RECIST v1.1, assessed by BICR.
OS in the all-patient population Up to approximately 3 years OS is defined as the time from randomization until death from any cause.
Time to deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26) in the RAS G12 and all-patient populations Up to approximately 3 years TTD is defined as the time from randomization to the first occurrence of deterioration as defined by a change of at least 10 points, or death, whichever occurs first, in each subscale in EORTC QLQ-PAN26.
Time to deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in the RAS G12 and all-patient populations Up to approximately 3 years TTD is defined as the time from randomization to the first occurrence of deterioration as defined by a change of at least 10 points, or death, whichever occurs first, in each subscale and global QoL score in EORTC QLQ-C30.
Objective response per investigator in RAS G12 and all- patient populations Up to approximately 3 years Objective response is defined as PR or CR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by the investigator.
Duration of response (DOR) in RAS G12 and all-patient populations Up to approximately 3 years DOR is defined as time from first evidence of objective response (PR or CR) to disease progression or death due to any cause, whichever occurs first, as assessed by BICR and by the investigator.
Time to response (TTR) in RAS G12 and all-patient populations Up to approximately 3 years TTR is defined as time from randomization to first evidence of objective response (PR or CR), as assessed by BICR and by the investigator.
Percentage of patients with adverse events (AEs) Up to approximately 3 years Pharmacokinetics of RMC-6236 in RAS G12 and all-patient populations Up to approximately 3 years Pharmacokinetics are defined by blood concentrations of RMC-6236 over time.
Trial Locations
- Locations (47)
Hospital 12 de Octubre
🇪🇸Madrid, Spain
City of Hope-Duarte
🇺🇸Duarte, California, United States
University of Miami Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Osaka International Cancer
🇯🇵Osaka, Japan
Hospital Unversitari
🇪🇸Barcelona, Spain
Hospital Clinico de Valencia
🇪🇸Valencia, Spain
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Mayo Clinic
🇺🇸Phoenix, Arizona, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
UCLA
🇺🇸Los Angeles, California, United States
UC San Diego Health Moores Cancer Center
🇺🇸San Diego, California, United States
Mission Hall UCSF
🇺🇸San Francisco, California, United States
Rocky Mountain Cancer
🇺🇸Aurora, Colorado, United States
Mayo Clinic Cancer Center
🇺🇸Jacksonville, Florida, United States
Cancer Care Centers of Brevard Inc
🇺🇸Palm Bay, Florida, United States
Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
NYU Lagone Health
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
Abramson Cancer Center Clinical Research Unit
🇺🇸Philadelphia, Pennsylvania, United States
Sarah Cannon Research Institute (Tennessee)
🇺🇸Nashville, Tennessee, United States
Texas Oncology Sammons
🇺🇸Dallas, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Texas Oncology - Central South
🇺🇸Irving, Texas, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Institut Paoli Calmettes
🇫🇷Marseille, France
Centre Eugene Marquis
🇫🇷Rennes, France
Hopital Paul Brousse
🇫🇷Villejuif, France
Gustave Roussy
🇫🇷Villejuif, France
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milan, Italy
IEO-Istituto Europeo di Oncologia
🇮🇹Milan, Italy
Azienda Ospedaliera
🇮🇹Pisa, Italy
National Cancer Center Hospital
🇯🇵Tokyo, Japan
Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Japan
Kanagawa Cancer Center
🇯🇵Yokohama, Japan
Pan-American Center for Oncology Trials
🇵🇷San Juan, Puerto Rico
Clinica Universidad de Navarra
🇪🇸Pamplona, Spain