Recruiting

Phase 1

Phase 2

RAS(ON) Inhibitor CombinationsStudy of RAS(ON) Inhibitors in Patients With Advanced RAS-mutated NSCLC

Sponsor:

Revolution Medicines, Inc.

Code:

NCT06162221

Conditions

Non-Small Cell Lung Cancer, NSCLC

KRAS, NRAS, HRAS-mutated NSCLC

KRAS G12C-mutated Solid Tumors, Lung Cancer

Lung Cancer Stage IV, Advanced Solid Tumor, Cancer

RAS G12D-mutated NSCLC

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

RMC-6291

RMC-6236

Pembrolizumab

Cisplatin

Carboplatin

Study Details

Brief summary:

The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors as a monotherapy or combined with Standard(s) of Care (SOC) or with each other.

The first four subprotocols include the following:

Subprotocol A: RMC-6291 +/- RMC-6236 + SOC Subprotocol B: RMC-6236 + SOC Subprotocol C: RMC-9805 +/- RMC-6236 + SOC Subprotocol D: RMC-9805

Conditions

Non-Small Cell Lung Cancer, NSCLC

KRAS, NRAS, HRAS-mutated NSCLC

KRAS G12C-mutated Solid Tumors, Lung Cancer

Lung Cancer Stage IV, Advanced Solid Tumor, Cancer

RAS G12D-mutated NSCLC

Study ID

NCT06162221

Start date

Jan 18, 2024

Status verified date

Jun, 2026

Completion date

Dec, 2028

Anticipated

Primary completion date

Jun, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion criteria:

All Patients (unless otherwise noted):

≥ 18 years of age
ECOG PS is 0 to 1
Adequate organ function as outlined by the study
Received prior standard therapy appropriate for tumor type and stage
Must have pathologically documented, locally advanced or metastatic KRAS G12C-mutated solid tumor malignancy (not amenable to curative surgery) (Subprotocol A)
Must have pathologically documented, locally advanced or metastatic RAS-mutated NSCLC (Subprotocol B)
Must have pathologically documented, locally advanced or metastatic RAS G12D-mutated NSCLC (Subprotocol C and Subprotocol D)

Exclusion criteria:

All Patients:

Primary central nervous system (CNS) tumors
Impaired gastrointestinal (GI) function that may significantly alter the absorption of RMC drugs
Major surgery < 28 days of first dose
Active or history of interstitial lung disease (ILD) or pneumonitis requiring steroids

Other inclusion/exclusion criteria may apply.

Study Design

Enrollment

616 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Subprotocol A: KRAS G12C-Mutated Solid Tumors

RMC-6291 (BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)

experimental: Subprotocol B: RAS-mutated NSCLC

RMC-6236 (QD) and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)

experimental: Subprotocol C: RAS G12D-mutated NSCLC

RMC-9805 (QD or BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W).

experimental: Subprotocol D: RAS G12D-mutated NSCLC

RMC-9805 (QD)

Interventions

RMC-6291

Oral tablet

RMC-6236

Oral tablet

Pembrolizumab

IV Infusion

Cisplatin

IV Infusion

Carboplatin

IV Infusion

Pemetrexed

IV infusion

RMC-9805

Oral Tablet

Primary outcome measure

Adverse events [ Time Frame: Up to 5 years ]
Dose limiting toxicities [ Time Frame: 21 days ]

Central Contacts and Locations

Central contacts

Revolution Medicines

1-844-2-REVMED medinfo@RevMed.com

Locations

Banner MD Anderson Cancer Center

Recruiting

Gilbert, Arizona, United States, 85234

UC Davis, Davis Comprehensive Cancer Center

Recruiting

Sacramento, California, United States, 95817

Contacts

Thanina Amirat

916-734-3186 tamirat@ucdavis.edu

University of California, San Diego Moores Cancer Center

Recruiting

San Diego, California, United States, 92037

Contacts

Kathy Velasco

858-822-5677 kcvelasco@health.ucsd.edu

UCSF Medical Center - Mission Bay

Recruiting

San Francisco, California, United States, 94158

Contacts

415-866-7866 lisa.tan@ucsf.edu

Stanford University - Stanford Cancer Institute

Recruiting

Stanford, California, United States, 94305

Contacts

650-498-6000 secure-thoraciccancertrials@lists.stanford.edu

Georgetown University Medical Center

Recruiting

Washington D.C., District of Columbia, United States, 20007

Contacts

Shannon Raue

202-784-5097 sr1657@georgetown.edu

Boca Raton Clinical Research Associates

Recruiting

Plantation, Florida, United States, 33322

Contacts

Sandra Perez

561-447-0614 sperez@brcrglobal.com

H Lee Moffitt Cancer Center and Research Institute

Recruiting

Tampa, Florida, United States, 33612

Contacts

Ana Aminpour

813-745-0287 anahid.aminpour@moffitt.org

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Thoracic KRAS Referrals

877-442-3324 dfcitopkrasmetclinicalresearch@partners.org

Nebraska Cancer Specialist

Recruiting

Grand Island, Nebraska, United States, 68803

New York University Langone Health

Recruiting

New York, New York, United States, 10016

Contacts

Salman Punekar

212-731-6228 Salman.punekar@nyulangone.org

Columbia University Medical Center

Recruiting

New York, New York, United States, 10032

Contacts

212-342-5162 Cancerclinicaltrials@cumc.columbia.edu

University Hospitals Cleveland Medical Center

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

216-844-3951

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

iddcreferrals@upmc.edu

Baptist Medical Center

Recruiting

Memphis, Tennessee, United States, 38120

Tennessee Oncology

Recruiting

Nashville, Tennessee, United States, 37203

The University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Alison Shaw

713-563-1235 ANTran1@mdanderson.org

NEXT Oncology Dallas

Recruiting

Irving, Texas, United States, 75039

Contacts

Idara Ukpong

972-893-8800 iukpong@nextoncology.com

NEXT Oncology Virginia

Recruiting

Fairfax, Virginia, United States, 22031

Contacts

Blake Patterson

703-783-4505 bpatterson@nextoncology.com

More Information

Sponsor

Revolution Medicines, Inc.

Last update posted

Oct 19, 2026

Last verified

Jun, 2026

Keywords

NSCLC
KRAS G12C
RAS Mutation
KRAS G12X
Non-Small Cell Lung Cancer
Lung Cancer
Lung Cancer Stage IV
Advanced Solid Tumor
Cancer
RAS G12D

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-24. This information was provided to ClinicalTrials.gov by Revolution Medicines, Inc. on 2026-10-19. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.