RecruitingPhase 2NCT07252739

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)

KEYMAKER-U01 Substudy 01J: A Randomized Phase 2 Umbrella Study With Rolling Arms of Investigational Agents for First-line Treatment of Participants With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With KRAS G12C Mutations


Sponsor

Merck Sharp & Dohme LLC

Enrollment

130 participants

Start Date

Dec 19, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria7

  • 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 Criteria16

  • 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

Interventions

DRUGMK-1084

Oral Administration

BIOLOGICALPembrolizumab

Intravenous administration

BIOLOGICALCetuximab

Intravenous administration

DRUGCarboplatin

Intravenous administration

DRUGPemetrexed

Intravenous administration


Locations(13)

Clermont Oncology Center ( Site 0041)

Clermont, Florida, United States

Deventer Ziekenhuis ( Site 0272)

Deventer, Overijssel, Netherlands

Severance Hospital Yonsei University Health System ( Site 0080)

Seoul, South Korea

Hacettepe Universite Hastaneleri ( Site 0140)

Ankara, Turkey (Türkiye)

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

Cherkasy, Cherkasy Oblast, Ukraine

Medical Center "Mriya Med-Service"-Clinical Research Department ( Site 0465)

Kryvyi Rih, Dnipropetrovsk Oblast, Ukraine

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

Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine

Limited Liability Company Ukrainian Center of Tomotherapy-Department of Chemotherapy ( Site 0467)

Kropyvnytskyi, Kirovohrad Oblast, Ukraine

Lviv Territorial Medical Union Multidisciplinary Clinical Hospital ( Site 0133)

Lviv, Lviv Oblast, Ukraine

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

Vinnitsya, Vinnytsia Oblast, Ukraine

Uzhhorod Municipal Multidisciplinary Clinical Hospital of Uzhhorod City Council ( Site 0137)

Uzhhorod, Zakarpattia Oblast, Ukraine

VISION PARTNER Medical Centre ( Site 0135)

Kyiv, Ukraine

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

Kyiv, Ukraine

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NCT07252739


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