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

Phase 3RecruitingNCT07805954

Revolution Medicines, Inc.400 enrolled

Overview

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.

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

400

Conditions

Pancreatic Cancer Pancreatic Cancer Metastatic PDAC PDAC - Pancreatic Ductal Adenocarcinoma

Interventions

daraxonrasibDRUG

oral tablets

gemcitabineDRUG

intravenous (IV) infusion

nab-paclitaxelDRUG

IV infusion

zoldonrasibDRUG

oral tablets

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Progression free survival (PFS)

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 Investigator.