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NCT Number: NCT07777822

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

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.

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Key information

Conditions

NSCLC Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Cancer (NSCLC) Lung Diseases Lung Neoplasms Metastatic NSCLC - Non-Small Cell Lung Cancer Metastatic Non-Squamous Non-Small Cell Lung Cancer Neoplasms Neoplasms by Site Non-Small Cell Lung Cancer NSCLC Non-Squamous Non Small Cell Lung Cancer Non-small Cell Lung Cancer Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Florida Clinical Trials Group, LLC

Plantation, Florida, 33322, United States

Location status: Recruiting

Location contact

Sandra Perez

CONTACT

[email protected]

772-297-3057 ext. Ext 102

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Zoldonrasib

Drug

oral tablets

Placebo

Drug

oral tablets

Pembrolizumab

Drug

IV infusion or Subcutaneous injection

Pemetrexed + Cisplatin /Carboplatin

Drug

IV infusion of either pemetrexed + cisplatin or pemetrexed + carboplatin

Other names: Platinum-based chemotherapy doublet

Primary outcomes

  1. Progression free survival (PFS)

    Time frame: Up to approximately 5 years

    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).

Secondary outcomes

  1. Overall survival (OS)

    Time frame: Up to approximately 5 years

    OS is defined as the time from randomization until death from any cause.

  2. Objective response rate (ORR)

    Time frame: Up to approximately 5 years

    Objective response is defined as partial response (PR) or complete response (CR) as assessed per RECIST v1.1 by BICR.

  3. Duration of response (DOR)

    Time frame: Up to approximately 5 years

    DOR is defined as time from first evidence of objective response (PR or CR) to disease progression or death due to any cause, whichever occurs first. Response and progression are per RECIST v1.1, as assessed by BICR.

  4. Incidence of adverse events (AEs)

    Time frame: Up to approximately 5 years

    Percentage of patients with AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5

  5. Changes in vital signs

    Time frame: Up to approximately 5 years

    Number of patients with changes in vital signs.

  6. Changes in clinical laboratory test values

    Time frame: Up to approximately 5 years

    Number of patients with changes in clinical laboratory test values.

  7. Quality of life as assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

    Time frame: Up to approximately 5 years

    EORTC QLQ-C30 is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea and vomiting, and pain), 7 single item scales (pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a 2-item global health status/quality of life scale. Change from baseline in EORTC QLQ-C30 physical functioning scale and global health status will be assessed. Higher scores on functional scales reflect better functioning, whereas higher scores on symptom scales reflect higher symptom burden.

  8. Time to confirmed deterioration in physical function and global health status, as measured by EORTC QLQ-C30

    Time frame: Up to approximately 5 years

    Time to confirmed deterioration in physical functioning subscale and overall global health status scale, as measured by EORTC QLQ-C30. Higher scores on the Higher scores on the EORTC QLQ-C30 functional scales reflect better functioning, whereas higher scores on symptom the scales reflect higher symptom burden. Time to confirmed deterioration in EORTC QLQ-C30 physical functioning subscale and overall health status scale is defined as the time from randomization until the date of the first clinically meaningful deterioration, or death.

  9. Changes in Non-Small Cell Lung Cancer (NSCLC)-related symptoms, measured by the NSCLC-Symptom Assessment Questionnaire (NSCLC-SAQ)

    Time frame: Up to approximately 5 years

    The NSCLC-SAQ is a participant reported outcome measure with seven items assessing key NSCLC symptoms such as: cough, pain, dyspnea, fatigue, and appetite. Change from baseline in pulmonary symptoms of cough and dyspnea will be evaluated, with higher scores indicating more severe symptoms.

  10. Time to Confirmed Deterioration of NSCLC-related symptoms, as measured by NSCLC-SAQ

    Time frame: Up to approximately 5 years

    Time to confirmed deterioration in patient-reported pulmonary symptoms of cough and dypsnea, as measured by NSCLC-SAQ. Higher scores for the pulmonary symptoms on the NSCLC-SAQ indicate more severe symptoms. Time to confirmed deterioration in NSCLC-SAQ measures is defined as the time from randomization until the date of the first clinically meaningful deterioration, or death.

  11. Concentration of zoldonrasib in Arm A

    Time frame: Up to Cycle 5 Day 1 (each cycle is 21 days)

    Pre-dose trough and post-dose blood concentrations of zoldonrasib at selected visits.

Study contacts

Contact information is provided by the study sponsor or research team.

Revolution Medicines Study Director

CONTACT

[email protected]

1-844-2-REVMED

Sponsors and collaborators

Lead sponsor

Revolution Medicines, Inc.

Industry

Registry information

Official study title

A Randomized, Double-blind, Phase 3 Study of Pembrolizumab + Pemetrexed + Platinum Chemotherapy With or Without Zoldonrasib (RMC-9805) as First Line Treatment in Patients With Metastatic Non-squamous RAS G12D-Mutated Non-small Cell Lung Cancer (RASolve 308)

Acronym: RASolve 308

Important dates

Study start
2026
Primary completion
2029
Study completion
2031
First posted
Aug 20, 2026
Registry last updated
Aug 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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