RASolute 303: A Phase 3 Global, Multicenter, Open-label, Randomized, 3-Arm Study of Daraxonrasib Monotherapy or Daraxonrasib Plus Gemcitabine and Nab-paclitaxel Versus Gemcitabine and Nab-paclitaxel as a First-Line Treatment for Patients With Metastatic Pancreatic Adenocarcinoma
Overview
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Revolution Medicines, Inc.
- Enrollment
- 900
- Locations
- 2
- Primary Endpoint
- Progression free survival (PFS)
Overview
Brief Summary
The purpose of this study is to evaluate the safety and efficacy of an investigational RAS(ON) inhibitor administered as monotherapy or in combination with chemotherapy, compared with standard of care (SOC) chemotherapy alone.
Detailed Description
This is a global, randomized, open-label, Phase 3 study designed to evaluate whether treatment with daraxonrasib monotherapy or daraxonrasib plus gemcitabine and nab-paclitaxel will improve progression-free survival and/or overall survival compared with standard gemcitabine and nab-paclitaxel when given as first-line treatment in patients with metastatic pancreatic adenocarcinoma.
Patients will be randomized to one of three arms: daraxonrasib (Arm A), daraxonrasib + gemcitabine and nab-paclitaxel (Arm B), or gemcitabine and nab-paclitaxel (Arm C).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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
- •Histologically or cytologically confirmed pancreatic adenocarcinoma.
- •Diagnosis of metastatic disease ≤ 6 weeks prior to informed consent.
- •Documented RAS mutation status, either mutant or wild-type.
- •Measurable disease per RECIST v1.
- •Adequate organ function (bone marrow, liver, kidney, coagulation).
- •Able to take oral medications.
Exclusion Criteria
- •Prior treatment with systemic anticancer therapy in metastatic setting or prior RAS-targeted therapy in any treatment setting.
- •Active or known history of untreated central nervous system metastatic disease.
- •Any conditions that may affect the ability to take or absorb study drug.
- •Major surgery within 28 days prior to randomization.
- •Patient is unable or unwilling to comply with protocol-required study visits or procedures.
Arms & Interventions
Arm C: gemcitabine and nab-paclitaxel
SOC chemotherapy
Intervention: nab-paclitaxel (Drug)
Arm A: daraxonrasib
study drug
Intervention: daraxonrasib (Drug)
Arm B: daraxonrasib + gemcitabine and nab-paclitaxel
study drug in combination with chemotherapy
Intervention: gemcitabine (Drug)
Arm B: daraxonrasib + gemcitabine and nab-paclitaxel
study drug in combination with chemotherapy
Intervention: nab-paclitaxel (Drug)
Arm B: daraxonrasib + gemcitabine and nab-paclitaxel
study drug in combination with chemotherapy
Intervention: daraxonrasib (Drug)
Arm C: gemcitabine and nab-paclitaxel
SOC chemotherapy
Intervention: gemcitabine (Drug)
Outcomes
Primary Outcomes
Progression free survival (PFS)
Time Frame: Up to approximately 2 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 Investigator.
Overall survival (OS)
Time Frame: Up to approximately 2 years
OS is defined as the time from randomization until death from any cause.
Secondary Outcomes
- Health-related outcome assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26)(Up to approximately 2 years)
- Quality of life as assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)(Up to approximately 2 years)
- Incidence of adverse events (AEs)(Up to approximately 2 years)
- Objective response rate (ORR)(Up to approximately 2 years)
- Duration of response (DOR)(Up to approximately 2 years)
- Concentration of daraxonrasib in Arm A and B(Up to Cycle 5 Day 1 (each cycle is 28 days))
- Changes in vital signs(Up to approximately 2 years)
- Changes in clinical laboratory test values(Up to approximately 2 years)