KEYMAKER-U01 Substudy 01J: A Study of Pembrolizumab Plus MK-1084 in Participants With Non-Small Cell Lung Cancer (NSCLC) With Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) G12C Mutations (MK-3475-01J/KEYMAKER-U01J)

NCT ID: NCT07252739

Last Updated: 2026-01-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

130 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-19

Study Completion Date

2033-01-14

Brief Summary

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Researchers want to learn if using a study medicine called MK-1084 can help treat NSCLC. MK-1084 is a type of treatment called targeted therapy for the Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C gene change. The goal of this study is to learn about the safety of MK-1084 and to learn how many people have the cancer get smaller or go away during the study treatment.

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Detailed Description

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Conditions

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Malignant Neoplasm

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Some outcome measures will be assessed by blinded independent central review (BICR), with assessor(s) blinded to intervention assignment.

Study Groups

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Arm 1

Participants receive 400 mg of Pembrolizumab every 6 weeks, Carbo platin every 3 weeks and 500 mg/m\^2 of Pemetrexed every 3 weeks.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

Intravenous administration

Carboplatin

Intervention Type DRUG

Intravenous administration

Pemetrexed

Intervention Type DRUG

Intravenous administration

Arm 2

Participants receive 400 mg of Pembrolizumab every 6 weeks, and MK-1084 dose regimen

Group Type EXPERIMENTAL

MK-1084

Intervention Type DRUG

Oral Administration

Pembrolizumab

Intervention Type BIOLOGICAL

Intravenous administration

Arm 3

Participants receive 400 mg of Pembrolizumab every 6 weeks, 500 mg/m\^2 Cetuximab every 2 weeks, and MK-1084 dose regimen

Group Type EXPERIMENTAL

MK-1084

Intervention Type DRUG

Oral Administration

Pembrolizumab

Intervention Type BIOLOGICAL

Intravenous administration

Cetuximab

Intervention Type BIOLOGICAL

Intravenous administration

Interventions

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MK-1084

Oral Administration

Intervention Type DRUG

Pembrolizumab

Intravenous administration

Intervention Type BIOLOGICAL

Cetuximab

Intravenous administration

Intervention Type BIOLOGICAL

Carboplatin

Intravenous administration

Intervention Type DRUG

Pemetrexed

Intravenous administration

Intervention Type DRUG

Other Intervention Names

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Keytruda MK-3475

Eligibility Criteria

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Inclusion Criteria

* Has histologically or cytologically confirmed diagnosis of advanced or metastatic nonsquamous Non-Small Cell Lung Cancer (NSCLC)
* Has tumor tissue or circulating tumor deoxyribonucleic acid (ctDNA) that demonstrates the presence of Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutations
* Can provide an archival tumor tissue sample or newly obtained core, incisional, excisional biopsy of a tumor lesion not previously irradiated
* Has recovered to ≤Grade 1 or baseline from any Adverse events (AEs) due to previous anticancer therapies and/or ≤Grade 2 neuropathy and/or endocrine-related AEs adequately treated with hormone replacement
* Has well controlled human immunodeficiency virus (HIV) on antiretroviral therapy (ART) if HIV-infected
* Has undetectable hepatitis B (HBV) viral load and have received HBV antiviral therapy for at least 4 weeks if hepatitis B surface antigen (HBsAg) positive
* Has undetectable hepatitis C (HCV) viral load if HCV-infected

Exclusion Criteria

* Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
* Has HIV-infection with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease
* Has uncontrolled, clinically significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of corrected QT interval corrected for heart rate by Fridericia's formula (QTcF) interval to \>470 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention
* Has received prior systemic anticancer therapy for advanced or metastatic NSCLC
* Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE) (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis
* Has received previous treatment with an agent targeting KRAS
* Has received prior systemic anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) and has not recovered to grade ≤ 1 or baseline from AE associated with anticancer therapy before allocation/randomization
* Has received radiation therapy to the lung that is \>30 Gray within 6 months of start of study intervention
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has a known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has a history of stem cell/solid organ transplant
* Has not adequately recovered from major surgery or has ongoing surgical complications
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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Clermont Oncology Center ( Site 0041)

Clermont, Florida, United States

Site Status RECRUITING

COMMUNAL NONPROFIT ENTERPRISE "CLINICAL CENTER OF ONCOLOGY, HEMATOLOGY, TRANSPLANTOLOGY AND PALLIATI ( Site 0139)

Cherkasy, Cherkasy Oblast, Ukraine

Site Status RECRUITING

Communal Non-Commercial Enterprise "Prykarpatski Clinical On-Surgery department #2 ( Site 0132)

Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine

Site Status RECRUITING

Communal Noncommercial Enterprise "Podillia Regional Oncolog-Cardiothoracic department ( Site 0131)

Vinnitsya, Vinnytsia Oblast, Ukraine

Site Status RECRUITING

VISION PARTNER Medical Centre ( Site 0135)

Kyiv, , Ukraine

Site Status RECRUITING

LIMITED LIABILITY COMPANY "MEDICAL CENTER "DOBROBUT-CLINIC" ( Site 0138)

Kyiv, , Ukraine

Site Status RECRUITING

Countries

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United States Ukraine

Central Contacts

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Toll Free Number

Role: CONTACT

1-888-577-8839

Facility Contacts

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Study Coordinator

Role: primary

386-538-3169

Study Coordinator

Role: primary

+380472370123

Study Coordinator

Role: primary

380978411455

Study Coordinator

Role: primary

380953105783

Study Coordinator

Role: primary

380989648486

Study Coordinator

Role: primary

+380671502987

Related Links

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https://www.merckclinicaltrials.com/

Merck Clinical Trials Information

Other Identifiers

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U1111-1321-3999

Identifier Type: REGISTRY

Identifier Source: secondary_id

2025-521939-36-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

3475-01J

Identifier Type: -

Identifier Source: org_study_id

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