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

Revolution Medicines

Status and phase: Enrolling; Phase 3

Conditions: PDAC - Pancreatic Ductal Adenocarcinoma; PDAC; Pancreatic Cancer

Treatments: Drug: 5-fluorouracil; Drug: leucovorin; Drug: Liposomal irinotecan; Drug: Oxaliplatin; Drug: Gemcitabine; Drug: nab-paclitaxel; Drug: Irinotecan; Drug: RMC-6236

Study type: Interventional

Funder types: Industry

Identifiers

NCT06625320

RMC-6236-302

Details and patient eligibility

About

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.

Full 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).

Enrollment: 460 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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460 participants in 2 patient groups

RMC-6236

Experimental group

Description:

Study drug

Treatment:

Drug: RMC-6236

Investigator's choice of standard of care therapy

Active Comparator group

Description:

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)

Treatment:

Drug: Irinotecan

Drug: nab-paclitaxel

Drug: Gemcitabine

Drug: Oxaliplatin

Drug: Liposomal irinotecan

Drug: leucovorin

Drug: 5-fluorouracil