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RecruitingInterventionalPhase 2

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

NCT ID: NCT07252739Sponsor: Merck Sharp & Dohme LLCLast updated: 2026-06-12

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.

Arms & interventions

  • DrugMK-1084

    Oral Administration

  • BiologicalPembrolizumab

    Intravenous administration

  • BiologicalCetuximab

    Intravenous administration

  • DrugCarboplatin

    Intravenous administration

  • DrugPemetrexed

    Intravenous administration

Outcome measures

Primary

  • Percentage of Participants with a Dose Limiting Toxicity (DLT)

    A DLT is defined as the occurrence of protocol-specified toxicities if assessed by the investigator to be possibly, probably, or definitely related to study intervention administration, excluding toxicities clearly not related to the drug.

    Time frame: Up to approximately 21 days

  • Percentage of Participants who Experience at Least One Adverse Event (AE)

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

    Time frame: Up to approximately 84 months

  • Percentage of Participants who Discontinue Study Intervention Due to an AE

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

    Time frame: Up to approximately 84 months

  • Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by Blinded Independent Central Review (BICR)

    ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented.

    Time frame: Up to approximately 84 months

Secondary

  • Duration of Response (DOR) per RECIST 1.1 as assessed by BICR

    Time frame: Up to approximately 84 months

  • Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR

    Time frame: Up to approximately 84 months

  • Overall Survival (OS)

    Time frame: Up to approximately 84 months

  • Area Under the Concentration-Time Curve (AUC) for MK-1084

    Time frame: At designated timepoints (up to approximately 44 days)

  • Maximum Concentration (Cmax) of MK-1084

    Time frame: At designated timepoints (up to approximately 44 days)

  • Trough Concentration (Ctrough) of MK-1084

    Time frame: At designated timepoints (up to approximately 84 months)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: 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 Criteria: The main exclusion criteria include but are not limited to the following: * 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

Study locations (3)

Clermont Oncology Center ( Site 0041)

Clermont, Florida, 34711

Recruiting
Study Coordinator · Contact

Sanford Health Roger Maris Cancer Center ( Site 0039)

Fargo, North Dakota, 58102

Recruiting
Study Coordinator · Contact

Sanford Cancer Center Oncology Clinic ( Site 0038)

Sioux Falls, South Dakota, 57104

Recruiting
Study Coordinator · Contact
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) | Cancerify