RASolute 302: A Phase 3 Multicenter, Open-label, Randomized Study of Daraxonrasib (RMC-6236) Versus Investigator's Choice of Standard of Care Therapy in Patients With Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)

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Investigational drug late phase More information Active drug More information Moderate burden on patient More information

Trial Details

Sponsor: Revolution Medicines, Inc. (industry)

Phase: 3

Start date: Oct. 16, 2024

Planned enrollment: 460

Trial ID: NCT06625320
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More trial details at ClinicalTrials.gov More info

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Investigational Drug AI Analysis

chevron Show for: RMC-6236 (A122)

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Goal: To determine whether the RAS(ON) inhibitor daraxonrasib (RMC-6236) improves progression-free survival and overall survival compared with investigator’s choice of standard chemotherapy in previously treated metastatic PDAC.

Patients: Adults (ECOG 0–1) with histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma, measurable disease by RECIST 1.1, adequate organ function, and documented RAS mutation status (mutant or wild type). One prior systemic line with a 5-FU–based or gemcitabine-based regimen is required. Key exclusions include prior direct RAS-targeted therapy, CNS metastases, major recent surgery, and conditions impairing oral drug absorption.

Design: Global, multicenter, open-label, randomized 1:1 Phase 3 trial comparing RMC-6236 versus investigator’s choice of standard-of-care chemotherapy. Stratification and blinded independent central review are used for efficacy assessments; enrollment planned for 460 participants.

Treatments: Experimental: RMC-6236 (daraxonrasib), an oral, multi-selective RAS(ON) inhibitor that forms a tri-complex with cyclophilin A and KRAS, blocking downstream effector binding to active, GTP-bound RAS. It targets both mutant and wild-type canonical RAS isoforms with particular activity in KRAS G12X tumors. In Phase 1/1b studies, RMC-6236 showed encouraging activity in previously treated PDAC, including an objective response rate of approximately 27% and median PFS of about 8 months in KRAS G12X second-line cohorts, with a generally manageable safety profile (predominantly grade 1–2 rash, diarrhea, nausea). Active comparator: Investigator’s choice of standard chemotherapy—gemcitabine plus nab-paclitaxel, modified FOLFIRINOX, liposomal irinotecan plus 5-FU/leucovorin, or FOLFOX, consistent with accepted regimens in the post–first-line setting.

Outcomes: Primary endpoints: PFS by BICR and OS in the RAS G12-mutant population. Key secondary endpoints: PFS and OS in the all-patient population; objective response rate (BICR and investigator) in RAS G12-mutant and all-patient populations; duration of response and time to response; patient-reported outcomes with time to deterioration on EORTC QLQ-PAN26 and QLQ-C30; safety (incidence of adverse events); and pharmacokinetics of RMC-6236. Assessments are planned for up to approximately 3 years.

Burden on patient: Moderate. As a Phase 3 trial, visit frequency and imaging are expected to mirror standard practice in metastatic PDAC, with periodic CT/MRI for RECIST assessments and routine labs. The oral investigational arm may reduce infusion visits compared with chemotherapy; however, on-treatment monitoring, safety labs, and patient-reported outcome questionnaires add visit time. The RMC-6236 arm includes pharmacokinetic blood sampling, particularly early in treatment, increasing blood draw frequency. No mandatory biopsies are specified, and there is no CNS imaging requirement unless clinically indicated, limiting additional procedural burden. Overall, burden is comparable to standard second-line PDAC care with added PK and PRO assessments.

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Institut Paoli Calmettes

Marseille, 13009, France

No email / No phone

Status: Active, not recruiting

Gustave Roussy

Villejuif, 94805, France

No email / No phone

Status: Active, not recruiting

Hopital Paul Brousse

Villejuif, 94804, France

No email / No phone

Status: Active, not recruiting

Centre Eugene Marquis

Rennes, 35042, France

No email / No phone

Status: Active, not recruiting

Nationales Centrum fur

Heidelberg, 69120, Germany

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Status: Recruiting

Charité Universitätsmedizin, Campus Berlin Mitte

Berlin, 13353, Germany

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Status: Recruiting

Universitatsklinikum Ulm

Ulm, 89081, Germany

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Status: Recruiting

Universitatsklinikum Ulm, Zentru

München, 81377, Germany

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Status: Recruiting

IEO-Istituto Europeo di Oncologia

Milan, Italy

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Status: Active, not recruiting

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

No email / No phone

Status: Active, not recruiting

Azienda Ospedaliera

Pisa, 56126, Italy

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Status: Active, not recruiting

IOV-Istituto Oncologico

Padua, 35128, Italy

No email / No phone

Status: Active, not recruiting

Osaka International Cancer

Osaka, 541-8567, Japan

No email / No phone

Status: Recruiting

Aichi Cancer Center

Nagoya, 4648681, Japan

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Status: Recruiting

National Cancer Center

Chiba, 277-8577, Japan

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Status: Recruiting

Kanagawa Cancer Center

Yokohama, 241-8515, Japan

[email protected] / No phone

Status: Recruiting

Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

[email protected] / +813-3520-0111

Status: Recruiting

National Cancer Center Hospital

Tokyo, 104-0045, Japan

No email / +81-03-3542-2511

Status: Recruiting

Pan-American Center for Oncology Trials

San Juan, 00907, Puerto Rico

No email / No phone

Status: Active, not recruiting

Hospital Clinico de Valencia

Valencia, 46010, Spain

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Clinica Universidad de Navarra

Pamplona, 31008, Spain

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Hospital 12 de Octubre

Madrid, 28041, Spain

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Hospital Unversitari

Barcelona, 08035, Spain

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Mayo Clinic Cancer Center - Phoenix

Phoenix, Arizona, 85054, United States

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Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

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Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

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UC San Diego Health Moores Cancer Center

San Diego, California, 92037, United States

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Mission Hall UCSF

San Francisco, California, 94158, United States

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City of Hope-Duarte

Duarte, California, 91010, United States

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UCLA

Los Angeles, California, 90095, United States

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Rocky Mountain Cancer

Aurora, Colorado, 80012, United States

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Mayo Clinic Cancer Center - Florida

Jacksonville, Florida, 32224, United States

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University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

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Cancer Care Centers of Brevard Inc

Palm Bay, Florida, 32909, United States

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Status: Active, not recruiting

Moffitt Cancer Center

Tampa, Florida, 33612, United States

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Status: Active, not recruiting

The Queen's Medical Center

Honolulu, Hawaii, 96813, United States

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The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

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Status: Active, not recruiting

Johns Hopkins

Baltimore, Maryland, 21287, United States

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Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

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Status: Active, not recruiting

University of Michigan

Ann Arbor, Michigan, 48109, United States

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Status: Active, not recruiting

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

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Status: Active, not recruiting

Mayo Clinic Cancer Center - Rochester

Rochester, Minnesota, 55905, United States

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Status: Active, not recruiting

Washington University

St Louis, Missouri, 63110, United States

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Status: Active, not recruiting

Memorial Sloan Kettering Cancer Center

New York, New York, 10022, United States

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Columbia University Medical Center

New York, New York, 10032, United States

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Status: Active, not recruiting

NYU Lagone Health

New York, New York, 10016, United States

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Status: Active, not recruiting

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

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Status: Active, not recruiting

Duke University Medical Center

Durham, North Carolina, 27710, United States

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Status: Active, not recruiting

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

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Status: Active, not recruiting

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

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Oregon Health and Science University

Portland, Oregon, 97239, United States

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Status: Active, not recruiting

Abramson Cancer Center Clinical Research Unit

Philadelphia, Pennsylvania, 19104, United States

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Status: Active, not recruiting

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

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Status: Active, not recruiting

Sarah Cannon Research Institute (Tennessee)

Nashville, Tennessee, 37203, United States

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Texas Oncology - Central South

Irving, Texas, 75063, United States

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Status: Active, not recruiting

Texas Oncology Sammons

Dallas, Texas, 75246, United States

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MD Anderson Cancer Center

Houston, Texas, 77030, United States

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Status: Active, not recruiting

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

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Status: Active, not recruiting

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

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Status: Active, not recruiting

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

No email / No phone

Status: Active, not recruiting

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