Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Metastatic KRAS G12D-Mutated Pancreatic Adenocarcinoma (RASolute 309)

Revolution Medicines

Status and phase: Enrolling; Phase 3

Conditions: Pancreatic Cancer Metastatic; Pancreatic Adenocarcinoma Metastatic; PDAC - Pancreatic Ductal Adenocarcinoma; PDAC; Pancreatic Adenocarcinoma; Pancreatic Adenosquamous Carcinoma; Pancreatic Ductal Adenocarcinoma (PDAC); Pancreatic Cancer

Treatments: Drug: nab-paclitaxel; Drug: zoldonrasib; Drug: daraxonrasib; Drug: gemcitabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT07805954

RMC-9805-309

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy of combination therapy with two investigational RAS(ON) inhibitors (daraxonrasib and zoldonrasib) compared to chemotherapy.

Full description

This is a global, randomized, open-label, Phase 3 study designed to evaluate whether treatment with daraxonrasib plus zoldonrasib will improve progression-free survival and/or overall survival compared with standard gemcitabine and nab-paclitaxel when given as first-line treatment in patients with metastatic KRAS G12D-mutated pancreatic adenocarcinoma.

Patients will be randomized to one of two arms: daraxonrasib + zoldonrasib (Arm A) or gemcitabine and nab-paclitaxel (Arm B).

Enrollment: 400 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 pancreatic adenocarcinoma, including adenosquamous carcinoma, not previously treated in the locally advanced unresectable or metastatic setting.
• No prior treatment in the locally advanced unresectable or metastatic setting
• Diagnosis of metastatic disease ≤ 6 weeks prior to informed consent.
• Documented KRAS G12D mutation status.
• Measurable disease per RECIST v1.1.
• Adequate organ function (bone marrow, liver, kidney, coagulation).

Exclusion criteria

• Mutation status with known driver mutations for which there are approved targeted therapies.
• Acinar cell carcinoma, pancreatic neuroendocrine tumors, tumors involving islet cells or islet cell neoplasms, and other non-adenocarcinoma pancreatic malignancies.
• Tumors determined to originate from non-pancreatic primary sites.
• Prior treatment with MAPK-pathway targeted therapy or administration of RAS-targeted vaccine in the metastatic setting.
• Active or known history of untreated central nervous system metastatic or leptomeningeal disease.
• Any conditions that may affect the ability to take or absorb study drug.
• Major surgery within 28 days prior to randomization.
• Patient is unable or unwilling to comply with protocol-required study visits or procedures.
• Additional inclusion & exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 2 patient groups

Arm A: daraxonrasib + zoldonrasib

Experimental group

Description:

combination of study drugs

Treatment:

Drug: daraxonrasib

Drug: zoldonrasib

Arm B: gemcitabine and nab-paclitaxel

Experimental group

Description:

chemotherapy

Treatment:

Drug: gemcitabine

Drug: nab-paclitaxel