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)
Sacituzumab tirumotecan (sac-TMT): Injection powder for intravenous infusion
Rescue 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.
Study 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
Sex
ALL
Min age
18 Years
Max age
—
Healthy 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 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
* Has a history of stem cell/solid organ transplant
* Has not adequately recovered from major surgery or has ongoing surgical complications
Primary outcome measure(s)
Percentage of Participants with a Dose Limiting Toxicity (DLT) — Up to approximately 21 days 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.
Percentage of Participants who Experience at Least One Adverse Event (AE) — Up to approximately 84 months 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.
Percentage of Participants who Discontinue Study Intervention Due to an AE — Up to approximately 84 months 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.
Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by Blinded Independent Central Review (BICR) — Up to approximately 84 months 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.
Trial sites (39)
Facility
City
Region
Status
Clermont Oncology Center ( Site 0041)
Clermont
Florida
Recruiting
Sanford Health Roger Maris Cancer Center ( Site 0039)
Fargo
North Dakota
Recruiting
Sanford Cancer Center Oncology Clinic ( Site 0038)
Sioux Falls
South Dakota
Recruiting
Fundacion Arturo Lopez Perez ( Site 0167)
Santiago
Region M. de Santiago
Recruiting
Centro de Oncología de Precisión ( Site 0160)
Santiago
Region M. de Santiago
Recruiting
Bradfordhill ( Site 0168)
Santiago
Region M. de Santiago
Recruiting
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School ( Site 0318)
Nanjing
Jiangsu
Recruiting
The First affiliated hospital of Nanchang University (Xianghu campus) ( Site 0306)
Nanchang
Jiangxi
Recruiting
Zhongshan Hospital Fudan University ( Site 0319)
Shanghai
Shanghai Municipality
Recruiting
West China Hospital, Sichuan University ( Site 0315)
Chengdu
Sichuan
Recruiting
Kuopion Yliopistollinen Sairaala ( Site 0261)
Kuopio
Northern Savonia
Recruiting
Vaasan Keskussairaala ( Site 0263)
Vaasa
Pohjanmaa
Recruiting
Turku University Hospital ( Site 0262)
Turku
Southwest Finland
Recruiting
HYKS Syöpätautien klinikka ( Site 0260)
Helsinki
Uusimaa
Recruiting
Evangelismos General Hospital of Athens ( Site 0200)
Athens
Attica
Recruiting
Hong Kong Integrated Oncology Centre ( Site 0232)
Central
Hong Kong
Recruiting
Queen Mary Hospital ( Site 0230)
Hong Kong
Hong Kong
Recruiting
Hong Kong United Oncology Centre ( Site 0231)
Kowloon
Hong Kong
Recruiting
Fondazione IRCCS Istituto Nazionale Dei Tumori ( Site 0175)
Milan
Lombardy
Recruiting
Deventer Ziekenhuis ( Site 0272)
Deventer
Overijssel
Recruiting
Leids Universitair Medisch Centrum ( Site 0273)
Leiden
South Holland
Recruiting
Severance Hospital Yonsei University Health System ( Site 0080)
Seoul
South Korea
Recruiting
Hospital Universitario Virgen de la Macarena ( Site 0093)
Seville
Spain
Recruiting
Bangkok Metropolitan Administration Medical College and Vajira Hospital ( Site 0351)
Bangkok
Bangkok
Recruiting
Faculty of Medicine Siriraj Hospital ( Site 0350)
Bangkok
Bangkok
Recruiting
Erciyes University ( Site 0145)
Talas
Kayseri
Recruiting
Baskent University Dr. Turgut Noyan Research and Training Center ( Site 0141)
Adana
Turkey (Türkiye)
Recruiting
Koç Üniversitesi Hastanesi ( Site 0142)
Adana
Turkey (Türkiye)
Recruiting
Liv Hospital Ankara ( Site 0146)
Ankara
Turkey (Türkiye)
Recruiting
Hacettepe Universite Hastaneleri ( Site 0140)
Ankara
Turkey (Türkiye)
Recruiting
COMMUNAL NONPROFIT ENTERPRISE CLINICAL CENTER OF ONCOLOGY, HEMATOLOGY, TRANSPLANTOLOGY AND PALLIATI ( Site 0139)
Cherkasy
Cherkasy Oblast
Recruiting
Medical Center "Mriya Med-Service"-Clinical Research Department ( Site 0465)
Kryvyi Rih
Dnipropetrovsk Oblast
Recruiting
Communal Non-Commercial Enterprise "Prykarpatski Clinical On-Surgery department #2 ( Site 0132)
Ivano-Frankivsk
Ivano-Frankivsk Oblast
Recruiting
Limited Liability Company Ukrainian Center of Tomotherapy-Department of Chemotherapy ( Site 0467)
Kropyvnytskyi
Kirovohrad Oblast
Recruiting
Lviv Territorial Medical Union Multidisciplinary Clinical Hospital ( Site 0133)
Lviv
Lviv Oblast
Recruiting
Communal Noncommercial Enterprise "Podillia Regional Oncolog-Cardiothoracic department ( Site 0131)
Vinnitsya
Vinnytsia Oblast
Recruiting
Uzhhorod Municipal Multidisciplinary Clinical Hospital of Uzhhorod City Council ( Site 0137)
Uzhhorod
Zakarpattia Oblast
Recruiting
VISION PARTNER Medical Centre ( Site 0135)
Kyiv
Ukraine
Active Not Recruiting
LIMITED LIABILITY COMPANY "MEDICAL CENTER "DOBROBUT-CLINIC" ( Site 0138)
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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