Evaluation of Co-formulated Pembrolizumab/Quavonlimab (MK-1308A) Versus Other Treatments in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer (CRC) (MK-1308A-008)
Colorectal Cancer
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Eligibility Criteria
Inclusion Criteria:
- Has a histologically confirmed diagnosis of Stage IV CRC adenocarcinoma (as defined by American Joint Committee on Cancer [AJCC] version 8)
- Has locally confirmed dMMR/MSI-H
- Has a life expectancy of at least 3 months
- Female participants are eligible to participate if not pregnant or breastfeeding, and not a woman of childbearing potential (WOCBP), or if a WOCBP then uses a contraceptive method that is highly effective or is abstinent on a long-term and persistent basis, during the intervention period and for at least 120 days after the last dose of study intervention
- Has measurable disease per RECIST 1.1 as assessed by the site and verified by BICR
- Submit an archival (within 5 years of Screening) or newly obtained tumor tissue sample that has not been previously irradiated; formalin-fixed, paraffin embedded (FFPE) blocks are preferred to slides.
- Has adequate organ function
Cohort A:
- Has been previously treated for their disease and radiographically progressed per RECIST 1.1 on or after or could not tolerate standard treatment, which must include all of the following agents if approved and locally available in the country where the participant is randomized:
- Fluoropyrimidine, irinotecan and oxaliplatin (capecitabine is acceptable as equivalent to fluorouracil in prior therapy)
- With or without an anti-vascular endothelial growth factor (VEGF) monoclonal antibody (e.g., bevacizumab)
- At least one of the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab or panitumumab) for rat sarcoma viral oncogene homolog (RAS) wild-type participants with left-sided tumors. Prior EGFR therapy is optional for patients with right sided RAS Wild-type (WT) tumors.
Cohort B:
- Has untreated Stage IV dMMR/MSI-H CRC with no prior chemotherapy or immunotherapy for this disease
Exclusion Criteria:
- Has received prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor
- Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
- Has not recovered adequately from a surgery procedure, and/or has any complications from a prior surgery before starting study intervention
- Has received prior radiotherapy within 2 weeks of start of study intervention
- Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose 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 medication
- Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab, quavonlimab, favezelimab, vibostolimab, MK-4830, and/or any of their excipients
- Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
- Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
- Has a history of acute or chronic pancreatitis
- Has neuromuscular disorders associated with an elevated creatine kinase
- Has urine protein ≥1 gram/24 hours
- Has an active infection requiring systemic therapy (e.g., tuberculosis, known viral or bacterial infections, etc.)
- Has a known history of Human Immunodeficiency Virus (HIV) infection
- Concurrent active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] positive and/or detectable Hepatitis B Virus [HBV] deoxyribonucleic acid [DNA]) and Hepatitis C virus (defined as anti-HCV antibody positive and detectable HCV ribonucleic acid [RNA] infection
- Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study intervention administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted.
- Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks before randomization/allocation
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
- Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
- Has had an allogenic tissue/solid organ transplant
Sites / Locations
- Mid Florida Cancer Center ( Site 1519)Recruiting
- University Cancer & Blood Center, LLC ( Site 1521)Recruiting
- University of Chicago Medical Center-Medicine - Section of Hematology/Oncology - Gastrointestinal PRecruiting
- Icahn School of Medicine at Mount Sinai ( Site 1528)Recruiting
- Hematology Oncology Associates of Rockland ( Site 1525)Recruiting
- UPMC Hillman Cancer Center ( Site 1516)
- Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 1509)Recruiting
- UT Southwestern Medical Center ( Site 1551)Recruiting
- Baylor Scott & White Medical Center - Temple-Division of Hematology/Oncology ( Site 1549)
- Northwest Medical Specialties, PLLC ( Site 1546)Recruiting
- UZ Brussel ( Site 0105)Recruiting
- Cliniques universitaires Saint-Luc-Medical Oncology ( Site 0104)Recruiting
- Université Catholique de Louvain-Namur - Centre Hospitalier -Oncology ( Site 0102)Recruiting
- UZ Leuven ( Site 0101)Recruiting
- AZ Delta vzw ( Site 0106)Recruiting
- The Moncton Hospital-Oncology ( Site 0307)Recruiting
- McGill University Health Centre-CIM - Oncology ( Site 0306)Recruiting
- Fundación Colombiana de Cancerología Clínica Vida ( Site 1606)Recruiting
- Clinica de la Costa S.A.S. ( Site 1608)Recruiting
- Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 1601)Recruiting
- Oncomédica S.A.S ( Site 1602)Recruiting
- Mediservis del Tolima IPS S.A.S ( Site 1609)Recruiting
- CIMCA-Hemato-Oncology ( Site 2101)Recruiting
- Hospital Metropolitano - Sede Lindora-Metropolitano Research Institute Sede Lindora ( Site 2102)Recruiting
- Rigshospitalet ( Site 1904)Recruiting
- Regionshospitalet Gødstrup ( Site 1901)Recruiting
- Aalborg Universitetshospital, Syd ( Site 1903)Recruiting
- Odense Universitetshospital ( Site 1902)Recruiting
- North Estonia Medical Centre Foundation-Chemotherapy ( Site 2301)Recruiting
- Tartu University Hospital ( Site 2302)Recruiting
- Assistance Publique Hôpitaux de Marseille - Hôpital de la Ti-Service d'Hepato-Gastro-Enterologie et
- Centre Georges François Leclerc ( Site 0506)Recruiting
- CHU Rangueil-Digestive oncology department ( Site 0502)
- Hopital Claude Huriez - CHU de Lille ( Site 0510)
- Centre Hospitalier Universitaire de Poitiers ( Site 0511)
- Hôpital Saint Antoine-Oncologie médicale ( Site 0508)
- Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie ( Site 0612)Recruiting
- Universitätsklinikum Marburg ( Site 0610)Recruiting
- Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung ( Site 0611)Recruiting
- Otto-von-Guericke-Universität Magdeburg-Klinik für Gastroenterologie, Hepatologie und InfektiologieRecruiting
- Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 0601)Recruiting
- Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0604)Recruiting
- Asklepios Altona-Oncology ( Site 0602)Recruiting
- Alexandra General Hospital of Athens-ONCOLOGY DEPT. ( Site 2704)Recruiting
- Evgenidion Hospital ( Site 2702)Recruiting
- University General Hospital of Heraklion-Internal Medicine-Oncology ( Site 2703)Recruiting
- European Interbalkan Medical Center-Oncology Department ( Site 2701)Recruiting
- CELAN,S.A ( Site 2202)Recruiting
- INTEGRA Cancer Institute-Oncology ( Site 2201)Recruiting
- MEDI-K CAYALA ( Site 2205)Recruiting
- Centro Regional de Sub Especialidades Médicas SA ( Site 2204)Recruiting
- Centro Medico Integral De Cancerología (CEMIC) ( Site 2203)Recruiting
- Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 2005)Recruiting
- Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Onkologiai Kozpont ( Site 2001)Recruiting
- Somogy Megyei Kaposi Mór Oktató Kórház-Oncology center ( Site 2010)Recruiting
- Semmelweis Egyetem-Belgyógyászati és Hematológiai Klinika ( Site 2002)Recruiting
- Debreceni Egyetem Klinikai Kozpont-Onkológiai Klinika ( Site 2008)Recruiting
- Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0802)Recruiting
- Istituto Nazionale Tumori IRCCS Fondazione Pascale-Department of Abdominal Oncology ( Site 0803)Recruiting
- Istituto Oncologico Veneto IRCCS ( Site 0804)Recruiting
- Kyungpook National University Chilgok Hospital-Hematology/oncology ( Site 1103)Recruiting
- Korea University Anam Hospital ( Site 1107)Recruiting
- Seoul National University Hospital-Internal Medicine ( Site 1101)Recruiting
- Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1104)Recruiting
- Asan Medical Center-Department of Oncology ( Site 1105)Recruiting
- Samsung Medical Center-Division of Hematology/Oncology ( Site 1102)Recruiting
- The Catholic Univ. of Korea Seoul St. Mary's Hospital-Medical Oncology ( Site 1106)Recruiting
- Hospital of Lithuanian University of Health Sciences Kauno klinikos ( Site 2402)Recruiting
- National Cancer Institute ( Site 2401)Recruiting
- VILNIUS UNIVERSITY HOSPITAL SANTAROS KLINIKOS ( Site 2403)Recruiting
- Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL) ( Site 2901)Recruiting
- DOLNOSLASKIE CENTRUM ONKOLOGII PULMONOLOGII I HEMATOLOGII ( Site 0920)Recruiting
- Powiatowe Centrum Zdrowia ( Site 0911)Recruiting
- Luxmed Onkologia sp. z o. o. ( Site 0915)Recruiting
- Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Onkologii i Radioterapii ( SiteRecruiting
- Mrukmed-Mrukmed ( Site 0901)Recruiting
- Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0903)Recruiting
- Fundeni Clinical Institute-Medical Oncology ( Site 2603)Recruiting
- Centrul medical Focus ( Site 2601)Recruiting
- Cardiomed SRL Cluj-Napoca ( Site 2602)Recruiting
- Centrul de Oncologie "Sfântul Nectarie"-Medical Oncology ( Site 2604)Recruiting
- Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 1001)
- Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology-Clinical Pharmacology and Chemotherapy
- First Moscow State Medical University I.M. Sechenov-Interhospital Institution Health Management Cl
- Rostov Cancer Research Institute ( Site 1014)
- GBUZ SPb CRPCstmc(o) ( Site 1005)
- Republican Clinical Oncology Dispensary-Chemotherapy #3 ( Site 1006)
- Hospital Universitario Central de Asturias-Medical Oncology ( Site 1203)Recruiting
- Hospital Universitario Marqués de Valdecilla ( Site 1202)Recruiting
- HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1206)Recruiting
- H.R.U Málaga - Hospital General ( Site 1207)Recruiting
- Fundación Instituto Valenciano de Oncología ( Site 1209)Recruiting
- Hospital Universitari Vall d'Hebron ( Site 1201)Recruiting
- Hospital Clinico San Carlos-Oncology Department ( Site 1204)Recruiting
- Baskent University Dr. Turgut Noyan Research and Training Center ( Site 1303)Recruiting
- Hacettepe Universitesi-oncology hospital ( Site 1301)Recruiting
- Ankara City Hospital-Medical Oncology ( Site 1306)Recruiting
- Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 1302)Recruiting
- TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1305)Recruiting
- Beatson West of Scotland Cancer Centre-Clinical Trials Unit ( Site 1401)Recruiting
- UCLH-Cancer Clinical Trials Unit ( Site 1402)Recruiting
- Velindre Cancer Centre-Research and Development ( Site 1415)Recruiting
- University Hospital Coventry & Warwickshire ( Site 1406)Recruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Active Comparator
Experimental
Experimental
Experimental
Experimental
Pembrolizumab
Pembrolizumab/Quavonlimab
Pembrolizumab/Favezelimab
Pembrolizumab/Vibostolimab
Pembrolizumab Plus MK-4830
Participants receive pembrolizumab 400 mg intravenously (IV) every 6 weeks (Q6W) for up to approximately 2 years.
Participants receive co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) Q6W for up to approximately 2 years.
Participants receive co-formulated pembrolizumab/favezelimab (200 mg/800 mg) every 3 weeks (Q3W) for up to approximately 2 years.
Participants receive co-formulated pembrolizumab/vibostolimab (200 mg/200 mg) Q3W for up to approximately 2 years.
Participants receive pembrolizumab 200 mg plus MK-4830 800 mg Q3W for up to approximately 2 years.