Pancreatic Cancer, PDAC, PDAC - Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
Pancreatic Cancer, PDAC, Pancreatic Ductal Adenocarcinoma, RAS, KRAS, NRAS, HRAS, RAS Wild-Type, RAS Q61 Mutation, RAS G12 Mutation, RAS G13 Mutation
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).
Interventions
DRUGRMC-6236
Oral Tablets
DRUGGemcitabine
intravenous (IV) infusion
DRUGnab-paclitaxel
IV infusion
DRUGIrinotecan
IV infusion
DRUGLiposomal irinotecan
IV infusion
DRUG5-fluorouracil
IV infusion
DRUGleucovorin
IV infusion
DRUGOxaliplatin
IV infusion
Sponsors
Revolution Medicines, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| OS in the all-patient population | Up to approximately 3 years | OS is defined as the time from randomization until death from any cause. |
Countries
France, Germany, Italy, Japan, Puerto Rico, Spain, United States
Outcome results
None listed