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

Study Overview

Phase 3 Study of Daraxonrasib (RMC-6236) 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.

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).

Pancreatic Cancer
PDAC
PDAC - Pancreatic Ductal Adenocarcinoma

DRUG: RMC-6236
DRUG: Gemcitabine
DRUG: nab-paclitaxel
DRUG: Irinotecan
DRUG: Liposomal irinotecan
DRUG: 5-fluorouracil
DRUG: leucovorin
DRUG: Oxaliplatin

RMC-6236-302

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2024-09-20	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-04-17
First Submitted that Met QC Criteria 2024-10-01	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-04-23
First Posted (ACTUAL) 2024-10-03	Results First Posted N/A	Last Verified 2024-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

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	DRUG: Gemcitabine intravenous (IV) infusion DRUG: nab-paclitaxel IV infusion DRUG: Irinotecan IV infusion DRUG: Liposomal irinotecan IV infusion DRUG: 5-fluorouracil IV infusion DRUG: leucovorin IV infusion DRUG: Oxaliplatin IV infusion

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

DRUG: Gemcitabine

intravenous (IV) infusion

DRUG: nab-paclitaxel

IV infusion

DRUG: Irinotecan

IV infusion

DRUG: Liposomal irinotecan

IV infusion

DRUG: 5-fluorouracil

IV infusion

DRUG: leucovorin

IV infusion

DRUG: Oxaliplatin

IV infusion

Primary Outcome Measures	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	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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Revolution Medicines

Phone Number: 1-844-2-REVMED

Email: medinfo@revmed.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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. Eligible 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.

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Study Director, Revolution Medicines

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record