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NCT07805954PHASE3Recruiting

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

Revolution Medicines, Inc.

Start Date

8/28/2026

Completion Date

4/1/2030

Summary

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.

Detailed 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).

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

daraxonrasib

DRUG

gemcitabine

DRUG

nab-paclitaxel

DRUG

zoldonrasib

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Conditions

Pancreatic CancerPancreatic Cancer MetastaticPDACPDAC - Pancreatic Ductal AdenocarcinomaPancreatic Ductal Adenocarcinoma (PDAC)Pancreatic Adenocarcinoma MetastaticPancreatic AdenocarcinomaPancreatic Adenosquamous Carcinoma

Locations

Moffitt Cancer Center

Tampa, Florida 33612

United States