Phase 3 Study of RMC-6236 in Patients with Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)

Phase 3

Recruiting

• Conditions: Pancreatic Cancer; PDAC; PDAC - Pancreatic Ductal Adenocarcinoma
• Interventions: Drug: RMC-6236; Drug: Gemcitabine; Drug: nab-paclitaxel; Drug: Irinotecan; Drug: Liposomal irinotecan; Drug: 5-fluorouracil; Drug: leucovorin; Drug: Oxaliplatin

• Registration Number: NCT06625320
• Lead Sponsor: Revolution Medicines, Inc.

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...

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Study Timeline

• Study First Submitted: 2024-09-20
• Status Verified: 2024-10
• Study First Submitted QC: 2024-10-01
• Study First Posted: 2024-10-03
• Study Start: 2024-10-16
• Last Update Submitted: 2024-12-09
• Last Update Posted: 2024-12-13
• Primary Completion: 2026-06
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 460

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. 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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RMC-6236	RMC-6236	Study drug
Investigator's choice of standard of care therapy	Gemcitabine	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)
Investigator's choice of standard of care therapy	nab-paclitaxel	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)
Investigator's choice of standard of care therapy	Irinotecan	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)
Investigator's choice of standard of care therapy	Liposomal irinotecan	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)
Investigator's choice of standard of care therapy	5-fluorouracil	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)
Investigator's choice of standard of care therapy	Oxaliplatin	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)
Investigator's choice of standard of care therapy	leucovorin	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)

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS) in the RAS G12-mutant population	Up to approximately 3 years	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)
Overall survival (OS) in the RAS G12-mutant population	Up to approximately 3 years	OS is defined as the time from randomization until death from any cause.

Secondary Outcome Measures

Name	Time	Method
PFS in the all-patient population	Up to approximately 3 years	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.
Objective response in the RAS G12 and all-patient populations	Up to approximately 3 years	Objective response is defined as partial response (PR) or completed response (CR) per RECIST v1.1, assessed by BICR.
OS in the all-patient population	Up to approximately 3 years	OS is defined as the time from randomization until death from any cause.
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	Up to approximately 3 years	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.
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	Up to approximately 3 years	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.
Objective response per investigator in RAS G12 and all- patient populations	Up to approximately 3 years	Objective response is defined as PR or CR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by the investigator.
Duration of response (DOR) in RAS G12 and all-patient populations	Up to approximately 3 years	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.
Time to response (TTR) in RAS G12 and all-patient populations	Up to approximately 3 years	TTR is defined as time from randomization to first evidence of objective response (PR or CR), as assessed by BICR and by the investigator.
Percentage of patients with adverse events (AEs)	Up to approximately 3 years
Pharmacokinetics of RMC-6236 in RAS G12 and all-patient populations	Up to approximately 3 years	Pharmacokinetics are defined by blood concentrations of RMC-6236 over time.

Trial Locations

Locations (7)

UCLA; 🇺🇸 Los Angeles, California, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States

Virginia Cancer Specialists; 🇺🇸 Fairfax, Virginia, United States

Pan-American Center for Oncology Trials; 🇵🇷 San Juan, Puerto Rico