Phase 3 Study of Daraxonrasib (RMC-6236) in Patients With Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)

NCT ID: NCT06625320

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 501 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-16
• Study Completion Date: 2027-12-31

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of a novel RAS(ON) inhibitor compared to standard(s) of care (SOC) treatment.

Detailed Description

This is a global, randomized, open-label, Phase 3 study designed to evaluate whether treatment with RMC-6236 will improve progression free survival (PFS) or overall survival (OS) compared to Investigator's choice of standard of care chemotherapy in patients with metastatic PDAC who were previously treated with one prior line of therapy with 5-fluorouracil (5-FU) based or gemcitabine-based regimen.

Patients will be randomized in a 1:1 ratio to receive RMC-6236 (Arm A) or Investigator's choice of standard of care chemotherapy (Arm B).

Conditions

Pancreatic Cancer; PDAC; PDAC - Pancreatic Ductal Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RMC-6236

Study drug

Group Type: EXPERIMENTAL

RMC-6236

Intervention Type: DRUG

Oral Tablets

Investigator's choice of standard of care therapy

Patients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments:

• Gemcitabine and nab-paclitaxel (GnP)
• Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX)
• Liposomal irinotecan (Nal-IRI + 5-FU/LV)
• Oxaliplatin, leucovorin and 5-FU IV (FOLFOX)

Group Type: ACTIVE_COMPARATOR

Gemcitabine

Intervention Type: DRUG

intravenous (IV) infusion

nab-paclitaxel

Intervention Type: DRUG

IV infusion

Irinotecan

Intervention Type: DRUG

IV infusion

Liposomal irinotecan

Intervention Type: DRUG

IV infusion

5-fluorouracil

Intervention Type: DRUG

IV infusion

leucovorin

Intervention Type: DRUG

IV infusion

Oxaliplatin

Intervention Type: DRUG

IV infusion

Interventions

RMC-6236

Oral Tablets

Intervention Type: DRUG

Gemcitabine

intravenous (IV) infusion

Intervention Type: DRUG

nab-paclitaxel

IV infusion

Intervention Type: DRUG

Irinotecan

IV infusion

Intervention Type: DRUG

Liposomal irinotecan

IV infusion

Intervention Type: DRUG

5-fluorouracil

IV infusion

Intervention Type: DRUG

leucovorin

IV infusion

Intervention Type: DRUG

Oxaliplatin

IV infusion

Intervention Type: DRUG

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 PDAC with metastatic disease.
• Measurable disease per RECIST 1.1.
• Adequate organ function (bone marrow, liver, kidney, coagulation)
• Documented RAS mutation status, either mutant or wild-type. RAS mutations defined as nonsynonymous mutations in KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61).
• Able to take oral medications.

Exclusion Criteria

• Prior therapy with direct RAS-targeted therapy (eg. degraders and/or inhibitors).
• History of or known central nervous system metastatic disease.
• Any conditions that may affect the ability to take or absorb study treatment
• Major surgery within 4 weeks prior to randomization.
• Patient is unable or unwilling to comply with protocol-required study visits or procedures

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Revolution Medicines, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Revolution Medicines

Locations

Hopital Paul Brousse

Villejuif, , France

Gustave Roussy

Villejuif, , France

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Mayo Clinic Cancer Center - Phoenix

Phoenix, Arizona, United States

City of Hope-Duarte

Duarte, California, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

UCLA

Los Angeles, California, United States

UC San Diego Health Moores Cancer Center

San Diego, California, United States

Mission Hall UCSF

San Francisco, California, United States

Rocky Mountain Cancer

Aurora, Colorado, United States

Mayo Clinic Cancer Center - Florida

Jacksonville, Florida, United States

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Cancer Care Centers of Brevard Inc

Palm Bay, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

The Queen's Medical Center

Honolulu, Hawaii, United States

The University of Chicago Medical Center

Chicago, Illinois, United States

Johns Hopkins

Baltimore, Maryland, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Mayo Clinic Cancer Center - Rochester

Rochester, Minnesota, United States

Washington University

St Louis, Missouri, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

NYU Lagone Health

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Oregon Health and Science University

Portland, Oregon, United States

Abramson Cancer Center Clinical Research Unit

Philadelphia, Pennsylvania, United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Sarah Cannon Research Institute (Tennessee)

Nashville, Tennessee, United States

Texas Oncology Sammons

Dallas, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Texas Oncology - Central South

Irving, Texas, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Institut Paoli Calmettes

Marseille, , France

Centre Eugene Marquis

Rennes, , France

Charité Universitätsmedizin, Campus Berlin Mitte

Berlin, , Germany

Nationales Centrum fur

Heidelberg, , Germany

Universitatsklinikum Ulm, Zentru

München, , Germany

Universitatsklinikum Ulm

Ulm, , Germany

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

IEO-Istituto Europeo di Oncologia

Milan, , Italy

IOV-Istituto Oncologico

Padua, , Italy

Azienda Ospedaliera

Pisa, , Italy

National Cancer Center

Chiba, , Japan

Aichi Cancer Center

Nagoya, , Japan

Osaka International Cancer

Osaka, , Japan

National Cancer Center Hospital

Tokyo, , Japan

Cancer Institute Hospital of JFCR

Tokyo, , Japan

Kanagawa Cancer Center

Yokohama, , Japan

Pan-American Center for Oncology Trials

San Juan, , Puerto Rico

Hospital Unversitari

Barcelona, , Spain

Hospital 12 de Octubre

Madrid, , Spain

Clinica Universidad de Navarra

Pamplona, , Spain

Hospital Clinico de Valencia

Valencia, , Spain

Countries

United States; France; Germany; Italy; Japan; Puerto Rico; Spain

Other Identifiers

RMC-6236-302

Identifier Type: -

Identifier Source: org_study_id