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NCT07621718PHASE3Recruiting

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 )

Revolution Medicines, Inc.

Start Date

5/22/2026

Completion Date

4/22/2030

Summary

The purpose of this study is to evaluate the efficacy of an investigational RAS(ON) inhibitor administered in combination with chemotherapy compared to placebo in combination with chemotherapy.

Detailed Description

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

Age Range: 18 years to No maximum

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.

Interventions

DRUG

Zoldonrasib

DRUG

Placebo

DRUG

Oxaliplatin

DRUG

Leucovorin (Calcium Folinate)

DRUG

5-Fluorouracil

DRUG

Irinotecan

DRUG

Gemcitabine (GEM)

DRUG

Nab-paclitaxel

Interested in This Trial?

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Conditions

Pancreatic CancerPancreatic Cancer MetastaticPDACPDAC - Pancreatic Ductal AdenocarcinomaPancreatic Ductal Adenocarcinoma (PDAC)Pancreatic Adenocarcinoma MetastaticPancreatic AdenocarcinomaPancreatic Adenosquamous Carcinoma

Locations

Mayo Clinic Arizona

Phoenix, Arizona 85054

United States

The University of Arizona Cancer Center-North Campus

Tucson, Arizona 85719

United States

Yale University

New Haven, Connecticut 06511

United States

University of Florida

Gainesville, Florida 32610

United States

Mayo Clinic Florida

Jacksonville, Florida 32224

United States

Moffitt Cancer Center

Tampa, Florida 33612

United States

Piedmont Cancer Institute

Atlanta, Georgia 30318

United States

Piedmont Healthcare

Atlanta, Georgia 30318

United States

University of Chicago Medical Center

Chicago, Illinois 60637

United States

Johns Hopkins University

Baltimore, Maryland 21287

United States

Dana Farber Cancer Institute

Boston, Massachusetts 02215

United States

Mayo Clinic Rochester

Rochester, Minnesota 55905

United States

Astera Cancer Care

East Brunswick, New Jersey 08816

United States

Rutgers Cancer University

New Brunswick, New Jersey 08901

United States

Columbia University Irving Medical Center

New York, New York 10032

United States

Duke Cancer Center

Durham, North Carolina 27710

United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee 37232

United States

University of Texas MD Anderson Cancer Center

Houston, Texas 77030

United States

Royal Marsden Hospital

London, SW3 6JJ

United Kingdom