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

140 participants

Start Date

Dec 19, 2025

Study Type

INTERVENTIONAL

Conditions

Malignant Neoplasm

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.

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study tests whether adding a new drug called MK-1084 to pembrolizumab (an established immune checkpoint drug also known as Keytruda) improves outcomes in patients with advanced or metastatic non-squamous non-small cell lung cancer that has a KRAS G12C gene mutation. This mutation is found in a subset of lung cancers and makes them difficult to treat. **You may be eligible if...** - You have confirmed advanced or metastatic non-squamous non-small cell lung cancer - Your tumor has a KRAS G12C mutation (confirmed by tumor tissue or a blood test) - You have not previously received systemic treatment for advanced or metastatic lung cancer - You can provide a tumor tissue sample - Your organ function and overall health are adequate **You may NOT be eligible if...** - You have small cell lung cancer - You have active, uncontrolled brain metastases or leptomeningeal disease (cancer in the fluid around the brain) - You have previously received a KRAS-targeted therapy - You have had a prior immunotherapy treatment that was stopped due to serious immune side effects - You have active autoimmune disease requiring systemic treatment - You have active or previous inflammatory bowel disease requiring immunosuppression - You have had a stem cell or solid organ transplant - You have significant uncontrolled heart disease Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGMK-1084

Oral Administration

BIOLOGICALPembrolizumab

Intravenous administration

BIOLOGICALCetuximab

Intravenous administration

BIOLOGICALSacituzumab tirumotecan (sac-TMT)

Injection powder for intravenous infusion

DRUGRescue medication

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.

Locations(38)

Clermont Oncology Center ( Site 0041)

Clermont, Florida, United States

Sanford Health Roger Maris Cancer Center ( Site 0039)

Fargo, North Dakota, United States

Sanford Cancer Center Oncology Clinic ( Site 0038)

Sioux Falls, South Dakota, United States

Fundacion Arturo Lopez Perez ( Site 0167)

Santiago, Region M. de Santiago, Chile

Centro de Oncología de Precisión ( Site 0160)

Santiago, Region M. de Santiago, Chile

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

Nanjing, Jiangsu, China

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

Nanchang, Jiangxi, China

Zhongshan Hospital Fudan University ( Site 0319)

Shanghai, Shanghai Municipality, China

West China Hospital, Sichuan University ( Site 0315)

Chengdu, Sichuan, China

Kuopion Yliopistollinen Sairaala ( Site 0261)

Kuopio, Northern Savonia, Finland

Vaasan Keskussairaala ( Site 0263)

Vaasa, Pohjanmaa, Finland

Turku University Hospital ( Site 0262)

Turku, Southwest Finland, Finland

HYKS Syöpätautien klinikka ( Site 0260)

Helsinki, Uusimaa, Finland

Evangelismos General Hospital of Athens ( Site 0200)

Athens, Attica, Greece

Hong Kong Integrated Oncology Centre ( Site 0232)

Central, Hong Kong

Hong Kong United Oncology Centre ( Site 0231)

Kowloon, Hong Kong

Queen Mary Hospital ( Site 0230)

Pokfulam, Hong Kong

Fondazione IRCCS Istituto Nazionale Dei Tumori ( Site 0175)

Milan, Lombardy, Italy

Deventer Ziekenhuis ( Site 0272)

Deventer, Overijssel, Netherlands

Leids Universitair Medisch Centrum ( Site 0273)

Leiden, South Holland, Netherlands

Severance Hospital Yonsei University Health System ( Site 0080)

Seoul, South Korea

Hospital Universitario Virgen de la Macarena ( Site 0093)

Seville, Spain

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

Bangkok, Bangkok, Thailand

Faculty of Medicine Siriraj Hospital ( Site 0350)

Bangkok, Bangkok, Thailand

Erciyes University ( Site 0145)

Talas, Kayseri, Turkey (Türkiye)

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

Adana, Turkey (Türkiye)

Koç Üniversitesi Hastanesi ( Site 0142)

Adana, Turkey (Türkiye)

Liv Hospital Ankara ( Site 0146)

Ankara, Turkey (Türkiye)

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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