Pembrolizumab with MK-1084 for lung cancer with a KRAS G12C mutation

Trial details

Who runs it

Merck Sharp & Dohme LLC

Trial code

NCT07252739EU 2025-521939-36-00

Record updated

10 November 2026

Original description

Researchers want to learn if using a study medicine called MK-1084 can help treat Non-Small Cell Lung Cancer (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.Read full original descriptionShow less

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

Researchers want to learn if using a study medicine called MK-1084 can help treat Non-Small Cell Lung Cancer (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.

Inclusion: The main inclusion criteria include but are not limited to the following:; 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: Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease; 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 not adequately recovered from major surgery or has ongoing surgical complications; 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 history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing; Has a known additional malignancy that is progressing or has required active treatment within the past 3 years; 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 (ILD) that required steroids, has current pneumonitis/ILD, or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments at screening; Has a history of stem cell/solid organ transplant; 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; The main exclusion criteria include but are not limited to the following:; Has a known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

ClinicalTrials.gov NCT07252739 · EU CTIS 2025-521939-36-00