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

Purpose

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.

Conditions

  • NSCLC
  • Non-small Cell Lung Cancer
  • Non-Small Cell Lung Cancer NSCLC
  • Non-Squamous Non Small Cell Lung Cancer
  • Lung Cancer (NSCLC)
  • Metastatic NSCLC - Non-Small Cell Lung Cancer
  • Metastatic Non-Squamous Non-Small Cell Lung Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)
Masking Description
Chemotherapy and pembrolizumab administration will be open label. This study is double-blind with respect to zoldonrasib versus placebo. Treatment assignments will remain blinded to Investigator, study center staff, patient, Sponsor and study vendors.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A: zoldonrasib + pembrolizumab + chemotherapy doublet 		study drug in combination with pembrolizumab and platinum-based chemotherapy doublet
  • Drug: zoldonrasib
    oral tablets
  • Drug: pembrolizumab
    IV infusion or Subcutaneous injection
  • Drug: pemetrexed + cisplatin /carboplatin
    IV infusion of either pemetrexed + cisplatin or pemetrexed + carboplatin
    Other names:
    • Platinum-based chemotherapy doublet
Placebo Comparator
Arm B: placebo + pembrolizumab + chemotherapy doublet 		placebo in combination with pembrolizumab and platinum-based chemotherapy doublet
  • Drug: Placebo
    oral tablets
  • Drug: pembrolizumab
    IV infusion or Subcutaneous injection
  • Drug: pemetrexed + cisplatin /carboplatin
    IV infusion of either pemetrexed + cisplatin or pemetrexed + carboplatin
    Other names:
    • Platinum-based chemotherapy doublet

Recruiting Locations

Florida Clinical Trials Group, LLC
Plantation, Florida 33322
Contact:
Sandra Perez
772-297-3057
perezs@floridactg.com

More Details

Status
Recruiting
Sponsor
Revolution Medicines, Inc.

Study Contact

Revolution Medicines Study Director
1-844-2-REVMED
medinfo@revmed.com

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).