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

NCT07777822 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: RMC-9805-308
• Study Type: interventional
• Target: 430
• Locations: 1 country
• Sites: 1

Brief 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.

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

Keywords

NSCLC; Non-Small Cell Lung Cancer; Non-Squamous Non Small Cell Lung Cancer; Metastatic Non-Squamous Non-Small Cell Lung Cancer; RAS; KRAS; NRAS; HRAS; RAS Mutation; Lung Cancer; G12D; RAS G12D

Outcome Measures

Primary Outcomes (1)

• 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 blinded independent central review (BICR).

  Up to approximately 5 years

Secondary Outcomes (11)

• Overall survival (OS)

  Up to approximately 5 years

• Objective response rate (ORR)

  Up to approximately 5 years

• Duration of response (DOR)

  Up to approximately 5 years

• Incidence of adverse events (AEs)

  Up to approximately 5 years

• Changes in vital signs

  Up to approximately 5 years

Study Arms (2)

Arm A: zoldonrasib + pembrolizumab + chemotherapy doublet

EXPERIMENTAL

study drug in combination with pembrolizumab and platinum-based chemotherapy doublet

Drug: zoldonrasib; Drug: pembrolizumab; Drug: pemetrexed + cisplatin /carboplatin

Arm B: placebo + pembrolizumab + chemotherapy doublet

PLACEBO COMPARATOR

placebo in combination with pembrolizumab and platinum-based chemotherapy doublet

Drug: Placebo; Drug: pembrolizumab; Drug: pemetrexed + cisplatin /carboplatin

Interventions

zoldonrasib DRUG

oral tablets

Arm A: zoldonrasib + pembrolizumab + chemotherapy doublet

Placebo DRUG

oral tablets

Arm B: placebo + pembrolizumab + chemotherapy doublet

pembrolizumab DRUG

IV infusion or Subcutaneous injection

Arm A: zoldonrasib + pembrolizumab + chemotherapy doublet; Arm B: placebo + pembrolizumab + chemotherapy doublet

pemetrexed + cisplatin /carboplatin DRUG

IV infusion of either pemetrexed + cisplatin or pemetrexed + carboplatin

Also known as: Platinum-based chemotherapy doublet

Arm A: zoldonrasib + pembrolizumab + chemotherapy doublet; Arm B: placebo + pembrolizumab + chemotherapy doublet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Revolution Medicines, Inc.: lead

Study Sites (1)

Florida Clinical Trials Group, LLC

Plantation, Florida, 33322, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

pembrolizumab; Pemetrexed; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Central Study Contacts

Revolution Medicines Study Director

CONTACT

1-844-2-REVMED; medinfo@revmed.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2026
• First Posted: August 20, 2026
• Study Start: August 14, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): February 1, 2031
• Last Updated: August 20, 2026

Record last verified: 2026-08

Locations

US (1)