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NCT07777822PHASE3Recruiting

Study of Pembrolizumab + Pemetrexed + Platinum Chemotherapy With or Without Zoldonrasib as First Line Treatment in Metastatic Non-squamous RAS G12D-Mutated NSCLC

Revolution Medicines, Inc.

Start Date

8/14/2026

Completion Date

2/1/2031

Summary

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

Detailed Description

This is a Phase 3, global, randomized, double-blind study designed to evaluate whether treatment with zoldonrasib in combination with pembrolizumab and platinum-based chemotherapy doublet will improve progression-free survival compared to placebo in combination with pembrolizumab and platinum-based chemotherapy doublet when given to patients with previously untreated, 1L metastatic RAS G12D-mutated, non-squamous non-small cell lung cancer (NSCLC). Patients will be randomized to one of two arms: zoldonrasib + pembrolizumab + platinum-based chemotherapy doublet (Arm A) or placebo + pembrolizumab + platinum-based chemotherapy doublet (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, previously untreated metastatic non-squamous NSCLC. * Known PD-L1 status * Documented RAS G12D mutation status. * Measurable disease per RECIST v1.1. * Adequate organ function (bone marrow, liver, kidney, coagulation, thyroid). * Able to take oral medications. Exclusion Criteria: * Prior treatment with systemic anticancer therapy in metastatic setting for NSCLC. * Prior systemic therapy with any RAS-directed therapy. * Untreated (symptomatic or asymptomatic) central nervous system metastatic disease. * Any conditions that may affect the ability to take or absorb study drug. * Major surgery on or within 28 days prior to randomization. * Patient is unable or unwilling to comply with protocol-required study visits or procedures. * Additional inclusion and exclusion criteria may apply

Interventions

DRUG

zoldonrasib

DRUG

Placebo

DRUG

pembrolizumab

DRUG

pemetrexed + cisplatin /carboplatin

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Conditions

NSCLCNon-small Cell Lung CancerNon-Small Cell Lung Cancer NSCLCNon-Squamous Non Small Cell Lung CancerLung Cancer (NSCLC)Metastatic NSCLC - Non-Small Cell Lung CancerMetastatic Non-Squamous Non-Small Cell Lung Cancer

Locations

Florida Clinical Trials Group, LLC

Plantation, Florida 33322

United States