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NCT07491445PHASE3Recruiting

Study of Daraxonrasib and Daraxonrasib + GnP as First-line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma

Revolution Medicines, Inc.

Start Date

3/9/2026

Completion Date

3/1/2029

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).

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 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.

Interventions

DRUG

daraxonrasib

DRUG

gemcitabine

DRUG

nab-paclitaxel

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Conditions

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

Locations

Honor Health Research Institute

Scottsdale, Arizona 85258

United States

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida 33612

United States

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland 21287

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

Comprehensive Cancer Centers of Nevada

Henderson, Nevada 89052

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

University of Cincinnati Cancer Center

Cincinnati, Ohio 45219

United States

Taylor Cancer Research Center

Maumee, Ohio 43537

United States

SCRI Oncology Partners

Nashville, Tennessee 37203

United States

SCRI - Texas Oncology Dallas

Dallas, Texas 95246

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

Virginia Cancer Specialists

Fairfax, Virginia 22031

United States

Virginia Mason Medical Center

Seattle, Washington 98101

United States

Calvary Mater Newcastle

Waratah, New South Wales 2298

Australia

National Cancer Center - East

Kashiwa, Chiba 277-8577

Japan

Cancer Institute Hospital - Japan Foundation for Cancer Research

Koto-Ku, Tokyo 135-8550

Japan

NHO Kyushu Cancer Center

Fukuoka, 811-1395

Japan

Kanagawa Cancer Canter

Kanagawa, 241-0815

Japan

Wakayama Medical University Hospital

Wakayama, 641-8510

Japan

Yamaguchi University Hospital

Yamaguchi, 755-8505

Japan