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)

NCT07252739 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: 3475-01JU1111-1321-39992025-521939-36-00
• Study Type: interventional
• Target: 140
• Locations: 13 countries
• Sites: 38

Brief Summary

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.

Conditions

Malignant Neoplasm

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  Up to approximately 84 months

Secondary Outcomes (6)

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

  Up to approximately 84 months

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

  Up to approximately 84 months

• Overall Survival (OS)

  Up to approximately 84 months

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

  At designated timepoints (up to approximately 44 days)

• Maximum Concentration (Cmax) of MK-1084

  At designated timepoints (up to approximately 44 days)

Study Arms (3)

Arm A- Pembrolizumab + MK-1084

EXPERIMENTAL

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

Drug: MK-1084; Biological: Pembrolizumab

Arm B- Pembrolizumab + MK-1084 + Cetuximab

EXPERIMENTAL

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

Drug: MK-1084; Biological: Pembrolizumab; Biological: Cetuximab

Arm C- Pembrolizumab + MK-1084 + sacituzumab tirumotecan (sac-TMT)

EXPERIMENTAL

Participants receive 400 mg of Pembrolizumab every 6 weeks, MK-1084 dose regimen, and 4 mg/kg sacituzumab tirumotecan (sac-TMT) every 2 weeks.

Drug: MK-1084; Biological: Pembrolizumab; Biological: Sacituzumab tirumotecan (sac-TMT); Drug: Rescue medication

Interventions

MK-1084 DRUG

Oral Administration

Arm A- Pembrolizumab + MK-1084; Arm B- Pembrolizumab + MK-1084 + Cetuximab; Arm C- Pembrolizumab + MK-1084 + sacituzumab tirumotecan (sac-TMT)

Pembrolizumab BIOLOGICAL

Intravenous administration

Also known as: Keytruda, MK-3475

Arm A- Pembrolizumab + MK-1084; Arm B- Pembrolizumab + MK-1084 + Cetuximab; Arm C- Pembrolizumab + MK-1084 + sacituzumab tirumotecan (sac-TMT)

Cetuximab BIOLOGICAL

Intravenous administration

Arm B- Pembrolizumab + MK-1084 + Cetuximab

Sacituzumab tirumotecan (sac-TMT) BIOLOGICAL

Injection powder for intravenous infusion

Also known as: MK-2870, SKB264

Arm C- Pembrolizumab + MK-1084 + sacituzumab tirumotecan (sac-TMT)

Rescue medication DRUG

Participants receive the following rescue medications, per approved product label, as premedication to study treatment to prevent hypersensitivity and/or infusion reactions: diphenhydramine (or equivalent histamine-1 \[Hl\] receptor antagonist), H2 receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent infusion, and granulocyte colony-stimulating factor (G-CSF). A steroid mouthwash (dexamethasone or equivalent) will be given as prophylaxis for stomatitis/oral mucositis.

Arm C- Pembrolizumab + MK-1084 + sacituzumab tirumotecan (sac-TMT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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 (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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (38)

Clermont Oncology Center ( Site 0041)

Clermont, Florida, 34711, United States

RECRUITING

Sanford Health Roger Maris Cancer Center ( Site 0039)

Fargo, North Dakota, 58102, United States

RECRUITING

Sanford Cancer Center Oncology Clinic ( Site 0038)

Sioux Falls, South Dakota, 57104, United States

RECRUITING

Fundacion Arturo Lopez Perez ( Site 0167)

Santiago, Region M. de Santiago, 7500921, Chile

RECRUITING

Centro de Oncología de Precisión ( Site 0160)

Santiago, Region M. de Santiago, 7560908, Chile

RECRUITING

Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School ( Site 0318)

Nanjing, Jiangsu, 210000, China

RECRUITING

The First affiliated hospital of Nanchang University (Xianghu campus) ( Site 0306)

Nanchang, Jiangxi, 330209, China

RECRUITING

Zhongshan Hospital Fudan University ( Site 0319)

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

West China Hospital, Sichuan University ( Site 0315)

Chengdu, Sichuan, 610066, China

RECRUITING

Kuopion Yliopistollinen Sairaala ( Site 0261)

Kuopio, Northern Savonia, 70200, Finland

RECRUITING

Vaasan Keskussairaala ( Site 0263)

Vaasa, Pohjanmaa, 65130, Finland

RECRUITING

Turku University Hospital ( Site 0262)

Turku, Southwest Finland, 20520, Finland

RECRUITING

HYKS Syöpätautien klinikka ( Site 0260)

Helsinki, Uusimaa, 00290, Finland

RECRUITING

Evangelismos General Hospital of Athens ( Site 0200)

Athens, Attica, 106 76, Greece

RECRUITING

Hong Kong Integrated Oncology Centre ( Site 0232)

Central, 0000, Hong Kong

RECRUITING

Hong Kong United Oncology Centre ( Site 0231)

Kowloon, Hong Kong

RECRUITING

Queen Mary Hospital ( Site 0230)

Pokfulam, Hong Kong

RECRUITING

Fondazione IRCCS Istituto Nazionale Dei Tumori ( Site 0175)

Milan, Lombardy, 20133, Italy

RECRUITING

Deventer Ziekenhuis ( Site 0272)

Deventer, Overijssel, 7416 SE, Netherlands

RECRUITING

Leids Universitair Medisch Centrum ( Site 0273)

Leiden, South Holland, 2333 ZA, Netherlands

RECRUITING

Severance Hospital Yonsei University Health System ( Site 0080)

Seoul, 03722, South Korea

RECRUITING

Hospital Universitario Virgen de la Macarena ( Site 0093)

Seville, 41009, Spain

RECRUITING

Bangkok Metropolitan Administration Medical College and Vajira Hospital ( Site 0351)

Bangkok, Bangkok, 10300, Thailand

RECRUITING

Faculty of Medicine Siriraj Hospital ( Site 0350)

Bangkok, Bangkok, 10700, Thailand

RECRUITING

Erciyes University ( Site 0145)

Talas, Kayseri, 38039, Turkey (Türkiye)

RECRUITING

Baskent University Dr. Turgut Noyan Research and Training Center ( Site 0141)

Adana, 1250, Turkey (Türkiye)

RECRUITING

Koç Üniversitesi Hastanesi ( Site 0142)

Adana, 34010, Turkey (Türkiye)

RECRUITING

Liv Hospital Ankara ( Site 0146)

Ankara, 06680, Turkey (Türkiye)

RECRUITING

Hacettepe Universite Hastaneleri ( Site 0140)

Ankara, 6230, Turkey (Türkiye)

RECRUITING

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

Cherkasy, Cherkasy Oblast, 18009, Ukraine

RECRUITING

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

Kryvyi Rih, Dnipropetrovsk Oblast, 50000, Ukraine

RECRUITING

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

Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76018, Ukraine

RECRUITING

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

Kropyvnytskyi, Kirovohrad Oblast, 25011, Ukraine

RECRUITING

Lviv Territorial Medical Union Multidisciplinary Clinical Hospital ( Site 0133)

Lviv, Lviv Oblast, 79059, Ukraine

RECRUITING

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

Vinnitsya, Vinnytsia Oblast, 21029, Ukraine

RECRUITING

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

Uzhhorod, Zakarpattia Oblast, 88000, Ukraine

RECRUITING

VISION PARTNER Medical Centre ( Site 0135)

Kyiv, 03022, Ukraine

RECRUITING

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

Kyiv, 03151, Ukraine

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Cetuximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Some outcome measures will be assessed by blinded independent central review (BICR), with assessor(s) blinded to intervention assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: November 28, 2025
• Study Start: December 19, 2025
• Primary Completion (Estimated): January 14, 2033
• Study Completion (Estimated): January 14, 2033
• Last Updated: July 30, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

HK (3); GR (1); TH (2); ES (1); TU (5); FI (4); KR (1); US (3); NL (2); UA (9); CN (4); CL (2); IT (1)