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

NCT07491445 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: RMC-6236-303
• Study Type: interventional
• Target: 900
• Locations: 15 countries
• Sites: 76

Brief 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.

Conditions

Pancreatic Cancer; Pancreatic Cancer Metastatic; PDAC; Pancreatic Adenocarcinoma Metastatic; PDAC - Pancreatic Ductal Adenocarcinoma; Pancreatic Ductal Adenocarcinoma (PDAC); Pancreatic Adenocarcinoma; Pancreatic Adenosquamous Carcinoma

Keywords

Pancreatic Cancer; PDAC; Pancreatic Ductal Adenocarcinoma; RAS; KRAS; NRAS; HRAS; RAS Wild-Type; RAS Mutation; Pancreatic Cancer Metastatic; Pancreatic Adenocarcinoma Metastatic; Pancreatic Adenosquamous Carcinoma; Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Progression free survival (PFS)

  PFS is defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is per response evaluation criteria in solid tumors (RECIST) v1.1 and as assessed by Investigator.

  Up to approximately 2 years

• Overall survival (OS)

  OS is defined as the time from randomization until death from any cause.

  Up to approximately 2 years

Secondary Outcomes (8)

• Objective response rate (ORR)

  Up to approximately 2 years

• Duration of response (DOR)

  Up to approximately 2 years

• Concentration of daraxonrasib in Arm A and B

  Up to Cycle 5 Day 1 (each cycle is 28 days)

• Health-related outcome assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26)

  Up to approximately 2 years

• Quality of life as assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

  Up to approximately 2 years

Study Arms (3)

Arm A: daraxonrasib

EXPERIMENTAL

study drug

Drug: daraxonrasib

Arm B: daraxonrasib + gemcitabine and nab-paclitaxel

EXPERIMENTAL

study drug in combination with chemotherapy

Drug: daraxonrasib; Drug: gemcitabine; Drug: nab-paclitaxel

Arm C: gemcitabine and nab-paclitaxel

ACTIVE COMPARATOR

SOC chemotherapy

Drug: gemcitabine; Drug: nab-paclitaxel

Interventions

daraxonrasib DRUG

oral tablets

Arm A: daraxonrasib; Arm B: daraxonrasib + gemcitabine and nab-paclitaxel

gemcitabine DRUG

intravenous (IV) infusion

Arm B: daraxonrasib + gemcitabine and nab-paclitaxel; Arm C: gemcitabine and nab-paclitaxel

nab-paclitaxel DRUG

IV infusion

Arm B: daraxonrasib + gemcitabine and nab-paclitaxel; Arm C: gemcitabine and nab-paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Revolution Medicines, Inc.: lead

Study Sites (82)

Mayo Clinic - Scottsdale

Phoenix, Arizona, 85054, United States

ACTIVE NOT RECRUITING

Honor Health Research Institute

Scottsdale, Arizona, 85258, United States

ACTIVE NOT RECRUITING

University of California Los Angeles Health - Hematology/Oncology

Los Angeles, California, 90095, United States

ACTIVE NOT RECRUITING

University of California San Francisco

San Francisco, California, 94158, United States

ACTIVE NOT RECRUITING

Mayo Clinic Cancer Center- Florida

Jacksonville, Florida, 32224, United States

ACTIVE NOT RECRUITING

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

ACTIVE NOT RECRUITING

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

ACTIVE NOT RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

ACTIVE NOT RECRUITING

Henry Ford Health System

Detroit, Michigan, 48202, United States

ACTIVE NOT RECRUITING

Mayo Clinic Cancer Center- Rochester

Rochester, Minnesota, 55905, United States

ACTIVE NOT RECRUITING

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, 89052, United States

ACTIVE NOT RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

ACTIVE NOT RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

ACTIVE NOT RECRUITING

University of Cincinnati Cancer Center

Cincinnati, Ohio, 45219, United States

ACTIVE NOT RECRUITING

Taylor Cancer Research Center

Maumee, Ohio, 43537, United States

ACTIVE NOT RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

ACTIVE NOT RECRUITING

SCRI - Texas Oncology Dallas

Dallas, Texas, 95246, United States

ACTIVE NOT RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

ACTIVE NOT RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

ACTIVE NOT RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

ACTIVE NOT RECRUITING

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

ACTIVE NOT RECRUITING

St. George Hospital

Kogarah, New South Wales, 2217, Australia

RECRUITING

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

RECRUITING

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

RECRUITING

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

RECRUITING

Epworth HealthCare

East Melbourne, Victoria, 3002, Australia

RECRUITING

Austin Health, Olivia Newton-John Cancer Research & Wellness Centre

Heidelberg, Victoria, 3084, Australia

RECRUITING

Krankenhaus der Barmherzigen Brüder Wien-Klinisch wissenschaftliche Studien

Vienna, 1020, Austria

RECRUITING

Institut Jules Bordet

Anderlecht, 1070, Belgium

RECRUITING

UZ Leuven (Univ Ziekenhuis Leuven)

Leuven, 3000, Belgium

RECRUITING

CEPON - Centro de Pesquisa Oncologicas de Santa Catarina

Florianópolis, Santa Catarina, 88034-000, Brazil

RECRUITING

CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia

São Paulo, 09060-650, Brazil

RECRUITING

Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1Z5, Canada

RECRUITING

McGill University - Dept. Oncology Clinical Research Program

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Klinikum der Universitaet Muenchen Campus Grosshadern

München, 81377, Germany

RECRUITING

The Chinese University of Hong Kong

Hong Kong, Sha Tin, Hong Kong

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

Istituto Oncologico Veneto IRCCS

Padova, 35128, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

RECRUITING

Azienda Ospedaliera Card. G. Panico

Tricase, 73039, Italy

RECRUITING

Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)

Verona, 37134, Italy

RECRUITING

National Cancer Center - East

Kashiwa, Chiba, 277-8577, Japan

RECRUITING

Cancer Institute Hospital - Japan Foundation for Cancer Research

Koto-Ku, Tokyo, 135-8550, Japan

RECRUITING

Chiba Cancer Center

Chiba, 260-8717, Japan

RECRUITING

NHO Kyushu Cancer Center

Fukuoka, 811-1395, Japan

RECRUITING

Kyushu University Hospital

Fukuoka, 812-8582, Japan

RECRUITING

Kanagawa Cancer Canter

Kanagawa, 241-0815, Japan

RECRUITING

Osaka International Cancer Institute

Osaka, 541-8567, Japan

RECRUITING

National Cancer Center - Tokyo

Tokyo, 104-0045, Japan

RECRUITING

Wakayama Medical University Hospital

Wakayama, 641-8510, Japan

RECRUITING

Yamaguchi University Hospital

Yamaguchi, 755-8505, Japan

RECRUITING

Erasmus Medisch Centrum

Rotterdam, 3015 GD, Netherlands

RECRUITING

St. Antonius Ziekenhuis

Utrecht, 3543 AZ, Netherlands

RECRUITING

National Cancer Centre Singapore

Singapore, 168583, Singapore

RECRUITING

Curie Oncology Pte Ltd

Singapore, 217562, Singapore

RECRUITING

Kyungpook National University Chilgok Hospital

Daegu, Republic of Korea, 41404, South Korea

RECRUITING

Dong-A University Hospital

Busan, 49201, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center - PPDS

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Hospital General Universitario Gregorio Marañon

Madrid, 28009, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Universitario La Paz - PPDS

Madrid, 28064, Spain

RECRUITING

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

Kaohsiung Medical University - Chung-Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

RECRUITING

China Medical University Hospital

Taichung, 40447, Taiwan

RECRUITING

National Cheng Kung University Hospital

Tainan, 704, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 100225, R.O.C, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

RECRUITING

Torbay Hospital

Torquay, Devon, TQ2 7AA, United Kingdom

RECRUITING

Queen Elizabeth Hospital - Birmingham

Birmingham, B15 2TH, United Kingdom

RECRUITING

NHS Cambridge of Addenbrooke Hospital

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

The Clatterbridge Cancer Centre

Liverpool, L7 8YA, United Kingdom

RECRUITING

Barts Hospital

London, EC1A 7BE, United Kingdom

RECRUITING

Royal Free Hospital

London, NW3 2QG, United Kingdom

RECRUITING

Guy's Hospital

London, SE1 9RT, United Kingdom

RECRUITING

Royal Marsden Hospital - London

London, SW3 6JJ, United Kingdom

RECRUITING

Sarah Cannon Research Institute UK

London, W1G 6AD, United Kingdom

RECRUITING

University College London Hospital

London, WC1E 6AG, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Revolution Medicines Study Director

CONTACT

1-844-2-REVMED; medinfo@revmed.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: March 10, 2026
• First Posted: March 24, 2026
• Study Start: March 9, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: October 2, 2026

Record last verified: 2026-09

Locations

AU (1); CA (3); KR (6); JP (10); SG (2); BR (2); GB (11); TW (5); NL (2); ES (4); US (21); IT (5); BE (2); DE (1); HK (1)