Clinical trial NCT06625320: Phase 3 Study of Daraxonrasib (RMC-6236) in Patients With Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Pancreatic Cancer
PDAC
PDAC - Pancreatic Ductal Adenocarcinoma
Keywords: Pancreatic Cancer
PDAC
Pancreatic Ductal Adenocarcinoma
RAS
KRAS
NRAS
HRAS
RAS Wild-Type
RAS Q61 Mutation
RAS G12 Mutation
RAS G13 Mutation
Lead sponsor: Revolution Medicines, Inc.
Sponsor class: INDUSTRY
First posted: 2024-10-03
Enrollment: 460
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Progression free survival (PFS) in the RAS G12-mutant population
timeFrame: Up to approximately 3 years
measure: Overall survival (OS) in the RAS G12-mutant population
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: PFS in the all-patient population
timeFrame: Up to approximately 3 years
measure: OS in the all-patient population
timeFrame: Up to approximately 3 years
measure: Objective response in the RAS G12 and all-patient populations
timeFrame: Up to approximately 3 years
measure: 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
timeFrame: Up to approximately 3 years
measure: 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
timeFrame: Up to approximately 3 years
measure: Objective response per investigator in RAS G12 and all- patient populations
timeFrame: Up to approximately 3 years
measure: Duration of response (DOR) in RAS G12 and all-patient populations
timeFrame: Up to approximately 3 years
measure: Time to response (TTR) in RAS G12 and all-patient populations
timeFrame: Up to approximately 3 years
measure: Percentage of patients with adverse events (AEs)
timeFrame: Up to approximately 3 years
measure: Pharmacokinetics of RMC-6236 in RAS G12 and all-patient populations
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Duarte
country: United States
facility: City of Hope-Duarte
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: San Diego
country: United States
facility: UC San Diego Health Moores Cancer Center
state: California
city: San Francisco
country: United States
facility: Mission Hall UCSF
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Cancer Center
state: Florida
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Palm Bay
country: United States
facility: Cancer Care Centers of Brevard Inc
state: Florida
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: NYU Lagone Health
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Abramson Cancer Center Clinical Research Unit
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute (Tennessee)
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology Sammons
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Irving
country: United States
facility: Texas Oncology - Central South
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Villejuif
country: France
facility: Hopital Paul Brousse
city: Villejuif
country: France
facility: Gustave Roussy
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milan
country: Italy
facility: IEO-Istituto Europeo di Oncologia
city: Pisa
country: Italy
facility: Azienda Ospedaliera
city: Osaka
country: Japan
facility: Osaka International Cancer
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: Cancer Institute Hospital of JFCR
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center
city: San Juan
country: Puerto Rico
facility: Pan-American Center for Oncology Trials
city: Barcelona
country: Spain
facility: Hospital Unversitari
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Valencia
country: Spain
facility: Hospital Clinico de Valencia
Study officials:
affiliation: Revolution Medicines
name: Study Director
role: STUDY_DIRECTOR
References: