Phase 3 Study of Daraxonrasib (RMC-6236) in Patients With Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) (RASolute 302)

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Cancer; PDAC; PDAC - Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: 5-fluorouracil; Drug: Oxaliplatin; Drug: nab-paclitaxel; Drug: Irinotecan; Drug: RMC-6236; Drug: leucovorin; Drug: Gemcitabine; Drug: Liposomal irinotecan

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).

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Rennes, France, 35042
    • Centre Eugene Marquis
  • Villejuif, France, 94804
    • Hôpital Paul Brousse
  • Villejuif, France, 94805
    • Gustave Roussy
• Germany
  • Berlin, Germany, 13353
    • Charité Universitätsmedizin, Campus Berlin Mitte
  • Heidelberg, Germany, 69120
    • Nationales Centrum fur
  • München, Germany, 81377
    • Universitatsklinikum Ulm, Zentru
  • Ulm, Germany, 89081
    • Universitatsklinikum Ulm
• Italy
  • Milan, Italy
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milan, Italy
    • IEO-Istituto Europeo di Oncologia
  • Padova, Italy, 35128
    • IOV-Istituto Oncologico
  • Pisa, Italy, 56126
    • Azienda Ospedaliera
• Japan
  • Chiba, Japan, 277-8577
    • National Cancer Center
  • Nagoya, Japan, 4648681
    • Aichi Cancer Center
  • Osaka, Japan, 541-8567
    • Osaka International Cancer
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital
  • Tokyo, Japan, 135-8550
    • Cancer Institute Hospital of JFCR
  • Yokohama, Japan, 241-8515
    • Kanagawa Cancer Center
• Puerto Rico
  • San Juan, Puerto Rico, 00907
    • Pan-American Center for Oncology Trials
• Spain
  • Barcelona, Spain, 08035
    • Hospital Unversitari
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra
  • Valencia, Spain, 46010
    • Hospital Clinico de Valencia
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Cancer Center - Phoenix
  • California
    • Duarte, California, United States, 91010
      • City of Hope-Duarte
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA
    • San Diego, California, United States, 92037
      • UC San Diego Health Moores Cancer Center
    • San Francisco, California, United States, 94158
      • Mission Hall UCSF
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Cancer Center - Florida
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Comprehensive Cancer Center
    • Palm Bay, Florida, United States, 32909
      • Cancer Care Centers of Brevard Inc
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • The Queen's Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center - Rochester
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10022
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10016
      • NYU Lagone Health
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center Clinical Research Unit
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute (Tennessee)
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology Sammons
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • Irving, Texas, United States, 75063
      • Texas Oncology - Central South
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RMC-6236; Study drug	Drug: RMC-6236; Oral Tablets
Active Comparator: 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)	Drug: 5-fluorouracil; IV infusion; Drug: Oxaliplatin; IV infusion; Drug: nab-paclitaxel; IV infusion; Drug: Irinotecan; IV infusion; Drug: leucovorin; IV infusion; Drug: Gemcitabine; intravenous (IV) infusion; Drug: Liposomal irinotecan; IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS) in the RAS G12-mutant population	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 blinded independent central review (BICR)	Up to approximately 3 years
Overall survival (OS) in the RAS G12-mutant population	OS is defined as the time from randomization until death from any cause.	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS in the all-patient population	PFS is defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is per RECIST v1.1 and as assessed by BICR.	Up to approximately 3 years
OS in the all-patient population	OS is defined as the time from randomization until death from any cause.	Up to approximately 3 years
Objective response in the RAS G12 and all-patient populations	Objective response is defined as partial response (PR) or completed response (CR) per RECIST v1.1, assessed by BICR.	Up to approximately 3 years
Time to deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26) in the RAS G12 and all-patient populations	TTD is defined as the time from randomization to the first occurrence of deterioration as defined by a change of at least 10 points, or death, whichever occurs first, in each subscale in EORTC QLQ-PAN26.	Up to approximately 3 years
Time to deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in the RAS G12 and all-patient populations	TTD is defined as the time from randomization to the first occurrence of deterioration as defined by a change of at least 10 points, or death, whichever occurs first, in each subscale and global QoL score in EORTC QLQ-C30.	Up to approximately 3 years
Objective response per investigator in RAS G12 and all- patient populations	Objective response is defined as PR or CR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by the investigator.	Up to approximately 3 years
Duration of response (DOR) in RAS G12 and all-patient populations	DOR is defined as time from first evidence of objective response (PR or CR) to disease progression or death due to any cause, whichever occurs first, as assessed by BICR and by the investigator.	Up to approximately 3 years
Time to response (TTR) in RAS G12 and all-patient populations	TTR is defined as time from randomization to first evidence of objective response (PR or CR), as assessed by BICR and by the investigator.	Up to approximately 3 years
Percentage of patients with adverse events (AEs)		Up to approximately 3 years
Pharmacokinetics of RMC-6236 in RAS G12 and all-patient populations	Pharmacokinetics are defined by blood concentrations of RMC-6236 over time.	Up to approximately 3 years

Collaborators and Investigators

• Sponsor: Revolution Medicines, Inc.
• Investigators: Study Director: Study Director, Revolution Medicines

Publications and helpful links

General Publications

• O'Reilly EM, Wainberg ZA, Hendifar AE, Borad MJ, Pietrantonio F, Pant S, Hammel P, Cremolini C, Manji GA, Oberstein PE, Garrido-Laguna I, Springfeld C, Azad NS, Ueno M, Chui SY, Zhang Y, Patel H, Lee Y, Salman Z, Wolpin BM; RASolute 302 Trial Investigators. Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer. N Engl J Med. 2026 May 31. doi: 10.1056/NEJMoa2605555. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: September 20, 2024
• First Submitted That Met QC Criteria: October 1, 2024
• First Posted (Actual): October 3, 2024

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma; KRAS; NRAS; PDAC; RAS; HRAS; RAS Wild-Type; RAS Q61 Mutation; RAS G12 Mutation; RAS G13 Mutation
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Camptothecin; Alkaloids; Enzymes and Coenzymes; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Oxaliplatin; Irinotecan; Gemcitabine; Fluorouracil; Leucovorin; 130-nm albumin-bound paclitaxel; irinotecan sucrosofate
• Other Study ID Numbers: RMC-6236-302

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No