Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-mutated Pancreatic Adenocarcinoma ( RASolute 305 )

Phase 3RecruitingNCT07621718

Revolution Medicines, Inc.670 enrolled

Overview

The purpose of this study is to evaluate the efficacy of an investigational RAS(ON) inhibitor administered in combination with chemotherapy compared to placebo in combination with chemotherapy.

This is a Phase 3, global, randomized, double-blind study designed to evaluate whether treatment with zoldonrasib in combination with Investigator choice of chemotherapy will improve progression-free survival or overall survival compared to placebo in combination with Investigator choice of chemotherapy when given to patients with previously untreated, 1L metastatic KRAS G12D-mutated pancreatic adenocarcinoma. Choice of chemotherapy (mFFX or GnP) will be at the discretion of the Investigator. Patients will be randomized to one of two arms: zoldonrasib + Investigator choice of chemotherapy (Arm A) or placebo + Investigator choice of chemotherapy (Arm B).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

670

Conditions

Pancreatic Cancer Pancreatic Cancer Metastatic PDAC

Interventions

ZoldonrasibDRUG

oral tablets

PlaceboDRUG

oral tablets

OxaliplatinDRUG

IV infusion

Leucovorin (Calcium Folinate)DRUG

IV infusion

5-FluorouracilDRUG

IV infusion

IrinotecanDRUG

IV infusion

Gemcitabine (GEM)DRUG

IV infusion

Nab-paclitaxelDRUG

IV infusion

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. * Diagnosis of metastatic disease ≤ 6 weeks prior to screening. * Documented KRAS G12D mutation status. * Measurable disease per RECIST v1.1. * Adequate organ function (bone marrow, liver, kidney, coagulation). * Able to take oral medications. Exclusion Criteria: * Prior treatment with systemic anticancer therapy in unresectable locally advanced or metastatic setting. * Prior systemic RAS-targeted therapy any time prior to randomization. * Presence of other known driver mutations with approved targeted therapies * Active or known history of untreated central nervous system metastatic 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.

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 assessed per response evaluation criteria in solid tumors (RECIST) v1.1 by Investigator.