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Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-mutated Pancreatic Adenocarcinoma ( RASolute 305 )

NCT07621718 · Revolution Medicines, Inc.
In plain English

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Official title
RASolute 305: A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Investigator Choice of Chemotherapy (Modified FOLFIRINOX or Gemcitabine Plus Nab-Paclitaxel) With or Without Zoldonrasib (RMC-9805) as First-line Treatment in Patients With Metastatic KRAS G12D-mutated Pancreatic Adenocarcinoma
About this study
This is a Phase 3, global, randomized, double-blind study designed to evaluate whether treatment with zoldonrasib in combination with Investigator choice of chemotherapy will improve progression-free survival or overall survival compared to placebo in combination with Investigator choice of chemotherapy when given to patients with previously untreated, 1L metastatic KRAS G12D-mutated pancreatic adenocarcinoma. Choice of chemotherapy (mFFX or GnP) will be at the discretion of the Investigator. Patients will be randomized to one of two arms: zoldonrasib + Investigator choice of chemotherapy (Arm A) or placebo + Investigator choice of chemotherapy (Arm B).
Eligibility criteria
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 screening. * Documented KRAS G12D mutation status. * 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 unresectable locally advanced or metastatic setting. * Prior systemic RAS-targeted therapy any time prior to randomization. * Presence of other known driver mutations with approved targeted therapies * 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.
Study design
Enrollment target: 670 participants
Allocation: randomized
Masking: double
Age groups: adult, older_adult
Timeline
Starts: 2026-05-22
Estimated completion: 2030-04-22
Last updated: 2026-06-02
Interventions
Drug: ZoldonrasibDrug: PlaceboDrug: OxaliplatinDrug: Leucovorin (Calcium Folinate)Drug: 5-FluorouracilDrug: IrinotecanDrug: Gemcitabine (GEM)Drug: Nab-paclitaxel
Primary outcomes
  • Progression free survival (PFS) (Up to approximately 4 years)
  • Overall survival (OS) (Up to approximately 4 years)
Sponsor
Revolution Medicines, Inc. · industry
Contacts & investigators
ContactRevolution Medicines Study Director · contact · medinfo@revmed.com · 1-844-2-REVMED
All locations (1)
Piedmont HealthcareRecruiting
Atlanta, Georgia, United States
Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-mutated Pancreatic Adenocarcinoma ( RASolute 305 ) · TrialPath