RecruitingInterventionalPhase 3

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

NCT ID: NCT07491445Sponsor: Revolution Medicines, Inc.Last updated: 2026-06-18

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).

Arms & interventions

Drugdaraxonrasib
oral tablets
Druggemcitabine
intravenous (IV) infusion
Drugnab-paclitaxel
IV infusion

Outcome measures

Primary

Progression free survival (PFS)
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.
Time frame: Up to approximately 2 years
Overall survival (OS)
OS is defined as the time from randomization until death from any cause.
Time frame: Up to approximately 2 years

Secondary

Objective response rate (ORR)
Time frame: Up to approximately 2 years
Duration of response (DOR)
Time frame: Up to approximately 2 years
Concentration of daraxonrasib in Arm A and B
Time frame: Up to Cycle 5 Day 1 (each cycle is 28 days)
Health-related outcome assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26)
Time frame: 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)
Time frame: Up to approximately 2 years
Incidence of adverse events (AEs)
Time frame: Up to approximately 2 years
Changes in vital signs
Time frame: Up to approximately 2 years
Changes in clinical laboratory test values
Time frame: Up to approximately 2 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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 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 v1.1. * 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.