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/KEYSTEP-008)

NCT04895722 | Active Not Recruiting Phase 2 DMC FDA Drug

• 6 other identifiers: 1308A-008MK-1308A-0082022-502100-70-00KEYSTEP-008U1111-1283-24342020-005114-18
• Study Type: interventional
• Target: 302
• Locations: 20 countries
• Sites: 105

Brief Summary

The purpose of this study is to assess the efficacy and safety of co-formulated pembrolizumab/quavonlimab versus other treatments in participants with MSI-H or dMMR Metastatic Stage IV Colorectal Cancer.

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

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

  Up to approximately 46 months

Secondary Outcomes (8)

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

  Up to approximately 46 months

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

  Up to approximately 46 months

• PFS per RECIST 1.1 as assessed by Investigator

  Up to approximately 46 months

• ORR per RECIST 1.1 as assessed by Investigator

  Up to approximately 46 months

• DOR per RECIST 1.1 as assessed by Investigator

  Up to approximately 46 months

Study Arms (5)

Pembrolizumab

ACTIVE COMPARATOR

Participants receive pembrolizumab 400 mg intravenously (IV) every 6 weeks (Q6W) for up to approximately 2 years.

Biological: Pembrolizumab

Pembrolizumab/Quavonlimab

EXPERIMENTAL

Participants receive co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) Q6W for up to approximately 2 years.

Biological: Pembrolizumab/Quavonlimab

Pembrolizumab/Favezelimab

EXPERIMENTAL

Participants receive co-formulated pembrolizumab/favezelimab (200 mg/800 mg) every 3 weeks (Q3W) for up to approximately 2 years.

Biological: Pembrolizumab/Favezelimab

Pembrolizumab/Vibostolimab

EXPERIMENTAL

Participants receive co-formulated pembrolizumab/vibostolimab (200 mg/200 mg) Q3W for up to approximately 2 years.

Biological: Pembrolizumab/Vibostolimab

Pembrolizumab Plus MK-4830

EXPERIMENTAL

Participants receive pembrolizumab 200 mg plus MK-4830 800 mg Q3W for up to approximately 2 years.

Biological: Pembrolizumab; Biological: MK-4830

Interventions

Pembrolizumab BIOLOGICAL

400 mg or 200 mg pembrolizumab administered via IV infusion.

Also known as: MK-3475, Keytruda®

Pembrolizumab; Pembrolizumab Plus MK-4830

Pembrolizumab/Quavonlimab BIOLOGICAL

Co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) fixed-dose combination (FDC) administered via IV infusion.

Also known as: MK-1308A

Pembrolizumab/Quavonlimab

Pembrolizumab/Favezelimab BIOLOGICAL

Co-formulated pembrolizumab/favezelimab (200 mg/800 mg) FDC administered via IV infusion

Also known as: MK-4280A

Pembrolizumab/Favezelimab

Pembrolizumab/Vibostolimab BIOLOGICAL

Co-formulated pembrolizumab/vibostolimab (200 mg/200 mg) FDC administered via IV infusion

Also known as: MK-7684A

Pembrolizumab/Vibostolimab

MK-4830 BIOLOGICAL

800 mg MK-4830 administered via IV infusion

Pembrolizumab Plus MK-4830

Eligibility Criteria

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

You may qualify if:

• 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 Stage IV dMMR/MSI-H CRC and radiographically progressed 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (109)

Mid Florida Cancer Center ( Site 1519)

Orange City, Florida, 32763, United States

Location

University Cancer & Blood Center, LLC ( Site 1521)

Athens, Georgia, 30607, United States

Location

University of Chicago Medical Center-Medicine - Section of Hematology/Oncology - Gastrointestinal P

Chicago, Illinois, 60637, United States

Location

Icahn School of Medicine at Mount Sinai ( Site 1528)

New York, New York, 10029, United States

Location

Hematology Oncology Associates of Rockland ( Site 1525)

Nyack, New York, 10960, United States

Location

UPMC Hillman Cancer Center ( Site 1516)

Pittsburgh, Pennsylvania, 15232, United States

Location

The West Clinic, PLLC dba West Cancer Center ( Site 1576)

Germantown, Tennessee, 38138, United States

Location

Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 1509)

Nashville, Tennessee, 37232, United States

Location

UT Southwestern Medical Center ( Site 1551)

Dallas, Texas, 75390, United States

Location

Baylor Scott & White Medical Center - Temple-Division of Hematology/Oncology ( Site 1549)

Temple, Texas, 76508, United States

Location

Northwest Medical Specialties, PLLC ( Site 1546)

Tacoma, Washington, 98405, United States

Location

UZ Brussel ( Site 0105)

Brussels, Bruxelles-Capitale, Region de, 1090, Belgium

Location

Cliniques universitaires Saint-Luc-Medical Oncology ( Site 0104)

Brussels, Bruxelles-Capitale, Region de, 1200, Belgium

Location

Université Catholique de Louvain-Namur - Centre Hospitalier -Oncology ( Site 0102)

Yvoir, Namur, 5530, Belgium

Location

UZ Leuven ( Site 0101)

Leuven, Vlaams-Brabant, 3000, Belgium

Location

AZ Delta vzw ( Site 0106)

Roeselare, West-Vlaanderen, 8800, Belgium

Location

The Moncton Hospital-Oncology ( Site 0307)

Moncton, New Brunswick, E1C 6Z8, Canada

Location

Sunnybrook Research Institute - Odette Cancer Centre ( Site 0316)

Toronto, Ontario, M4N 3M5, Canada

Location

McGill University Health Centre-CIM - Oncology ( Site 0306)

Montreal, Quebec, H4A 3J1, Canada

Location

Instituto de Cancerología ( Site 1610)

Medellín, Antioquia, 050025, Colombia

Location

Fundación Colombiana de Cancerología Clínica Vida ( Site 1606)

Medellín, Antioquia, 050030, Colombia

Location

Clinica de la Costa S.A.S. ( Site 1608)

Barranquilla, Atlántico, 080020, Colombia

Location

Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia ( Site 1611)

Bogotá, Bogota D.C., 111321, Colombia

Location

Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 1601)

Valledupar, Cesar Department, 200001, Colombia

Location

Oncomédica S.A.S ( Site 1602)

Montería, Departamento de Córdoba, 230002, Colombia

Location

Mediservis del Tolima IPS S.A.S ( Site 1609)

Ibagué, Tolima Department, 730006, Colombia

Location

CIMCA-Hemato-Oncology ( Site 2101)

San José, Provincia de San José, 1000, Costa Rica

Location

Hospital Metropolitano - Sede Lindora-Metropolitano Research Institute Sede Lindora ( Site 2102)

Santa Ana, Provincia de San José, 10903, Costa Rica

Location

Rigshospitalet ( Site 1904)

Copenhagen, Capital Region, 2100, Denmark

Location

Regionshospitalet Gødstrup ( Site 1901)

Herning, Central Jutland, 7400, Denmark

Location

Aalborg Universitetshospital, Syd ( Site 1903)

Aalborg, North Denmark, 9000, Denmark

Location

Odense Universitetshospital ( Site 1902)

Odense, Region Syddanmark, 5000, Denmark

Location

North Estonia Medical Centre Foundation-Chemotherapy ( Site 2301)

Tallinn, Harju, 13419, Estonia

Location

Tartu University Hospital ( Site 2302)

Tartu, Tartu, 50406, Estonia

Location

Assistance Publique Hôpitaux de Marseille - Hôpital de la Ti-Service d'Hepato-Gastro-Enterologie et

Marseille, Bouches-du-Rhone, 13385, France

Location

Centre Georges François Leclerc ( Site 0506)

Dijon, Cote-d Or, 21079, France

Location

CHU Rangueil-Digestive oncology department ( Site 0502)

Toulouse, Haute-Garonne, 31059, France

Location

Hopital Claude Huriez - CHU de Lille ( Site 0510)

Lille, Nord, 59037, France

Location

Centre Hospitalier Universitaire de Poitiers ( Site 0511)

Poitiers, Vienne, 86021, France

Location

Hôpital Saint Antoine-Oncologie médicale ( Site 0508)

Paris, 75571, France

Location

Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie ( Site 0612)

Munich, Bavaria, 81737, Germany

Location

Universitätsklinikum Marburg ( Site 0610)

Marburg, Hesse, 35043, Germany

Location

Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung ( Site 0611)

Essen, North Rhine-Westphalia, 45136, Germany

Location

Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 0601)

Dresden, Saxony, 01307, Germany

Location

Otto-von-Guericke-Universität Magdeburg-Klinik für Gastroenterologie, Hepatologie und Infektiologie

Magdeburg, Saxony-Anhalt, 39120, Germany

Location

Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0604)

Berlin, 10117, Germany

Location

Asklepios Altona-Oncology ( Site 0602)

Hamburg, 22763, Germany

Location

Alexandra General Hospital of Athens-ONCOLOGY DEPT. ( Site 2704)

Athens, Attica, 115 28, Greece

Location

Evgenidion Hospital ( Site 2702)

Athens, Attica, 115 28, Greece

Location

University General Hospital of Heraklion-Internal Medicine-Oncology ( Site 2703)

Heraklion, Irakleio, 715 00, Greece

Location

European Interbalkan Medical Center-Oncology Department ( Site 2701)

Thessaloniki, 57001, Greece

Location

CELAN,S.A ( Site 2202)

Guatemala City, 01010, Guatemala

Location

INTEGRA Cancer Institute-Oncology ( Site 2201)

Guatemala City, 01010, Guatemala

Location

MEDI-K CAYALA ( Site 2205)

Guatemala City, 01016, Guatemala

Location

Centro Regional de Sub Especialidades Médicas SA ( Site 2204)

Quetzaltenango, 09001, Guatemala

Location

Centro Medico Integral De Cancerología (CEMIC) ( Site 2203)

Quetzaltenango, 09002, Guatemala

Location

Pécsi Tudományegyetem Klinikai Központ-Onkoterápiás Intézet ( Site 2009)

Pécs, Baranya, 7624, Hungary

Location

Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 2005)

Kecskemét, Bács-Kiskun county, 6000, Hungary

Location

Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Onkologiai Kozpont ( Site 2001)

Szolnok, Jász-Nagykun-Szolnok, 5000, Hungary

Location

Somogy Megyei Kaposi Mór Oktató Kórház-Oncology center ( Site 2010)

Kaposvár, Somogy County, 7400, Hungary

Location

Semmelweis Egyetem-Belgyógyászati és Hematológiai Klinika ( Site 2002)

Budapest, 1088, Hungary

Location

Debreceni Egyetem Klinikai Kozpont-Onkológiai Klinika ( Site 2008)

Debrecen, 4032, Hungary

Location

Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0802)

Milan, Lombardy, 20133, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione Pascale-Department of Abdominal Oncology ( Site 0803)

Naples, 80131, Italy

Location

Istituto Oncologico Veneto IRCCS ( Site 0804)

Padua, 35128, Italy

Location

Hospital of Lithuanian University of Health Sciences Kauno klinikos ( Site 2402)

Kaunas, Kaunas County, 50161, Lithuania

Location

National Cancer Institute ( Site 2401)

Vilnius, Vilniaus Miestas, 08660, Lithuania

Location

VILNIUS UNIVERSITY HOSPITAL SANTAROS KLINIKOS ( Site 2403)

Vilnius, 08460, Lithuania

Location

Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL) ( Site 2901)

Amsterdam, North Holland, 1066CX, Netherlands

Location

DOLNOSLASKIE CENTRUM ONKOLOGII PULMONOLOGII I HEMATOLOGII ( Site 0920)

Wroclaw, Lower Silesian Voivodeship, 53-413, Poland

Location

Luxmed Onkologia sp. z o. o. ( Site 0915)

Warsaw, Masovian Voivodeship, 01-748, Poland

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Onkologii i Radioterapii ( Site

Warsaw, Masovian Voivodeship, 02-034, Poland

Location

Mrukmed-Mrukmed ( Site 0901)

Rzeszów, Podkarpackie Voivodeship, 35-021, Poland

Location

Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0903)

Koszalin, West Pomeranian Voivodeship, 75-581, Poland

Location

Powiatowe Centrum Zdrowia ( Site 0911)

Brzeziny, Łódź Voivodeship, 95-060, Poland

Location

Spitalul de Oncologie Monza Oncologie Medicala ( Site 2601)

Bucharest, București, 013812, Romania

Location

Fundeni Clinical Institute-Medical Oncology ( Site 2603)

Bucharest, București, 022328, Romania

Location

Cardiomed SRL Cluj-Napoca ( Site 2602)

Cluj-Napoca, Cluj, 400015, Romania

Location

Centrul de Oncologie "Sfântul Nectarie"-Medical Oncology ( Site 2604)

Craiova, Dolj, 200542, Romania

Location

Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 1001)

Saint Petersburg, Leningradskaya Oblast', 198255, Russia

Location

Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology-Clinical Pharmacology and Chemotherapy

Moscow, Moscow, 115478, Russia

Location

First Moscow State Medical University I.M. Sechenov-Interhospital Institution Health Management Cl

Moscow, Moscow, 119991, Russia

Location

Rostov Cancer Research Institute ( Site 1014)

Rostov-on-Don, Rostov Oblast, 344037, Russia

Location

GBUZ SPb CRPCstmc(o) ( Site 1005)

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

Republican Clinical Oncology Dispensary-Chemotherapy #3 ( Site 1006)

Kazan', Tatarstan, Respublika, 420029, Russia

Location

Kyungpook National University Chilgok Hospital-Hematology/oncology ( Site 1103)

Daegu, Taegu-Kwangyokshi, 41404, South Korea

Location

Korea University Anam Hospital ( Site 1107)

Seoul, 02841, South Korea

Location

Seoul National University Hospital-Internal Medicine ( Site 1101)

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1104)

Seoul, 03722, South Korea

Location

Asan Medical Center-Department of Oncology ( Site 1105)

Seoul, 05505, South Korea

Location

Samsung Medical Center-Division of Hematology/Oncology ( Site 1102)

Seoul, 06351, South Korea

Location

The Catholic Univ. of Korea Seoul St. Mary's Hospital-Medical Oncology ( Site 1106)

Seoul, 06591, South Korea

Location

Hospital Universitario Marqués de Valdecilla ( Site 1202)

Santander, Cantabria, 39008, Spain

Location

Hospital Universitari Vall d'Hebron ( Site 1201)

Barcelona, Catalonia, 08035, Spain

Location

HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1206)

Madrid, Madrid, Comunidad de, 28007, Spain

Location

H.R.U Malaga - Hospital General ( Site 1207)

Málaga, Malaga, 29010, Spain

Location

COMPLEJO HOSPITALARIO DE NAVARRA-oncologia médica ( Site 1210)

Pamplona, Navarre, 31009, Spain

Location

Hospital Universitario Central de Asturias-Medical Oncology ( Site 1203)

Oviedo, Principality of Asturias, 33011, Spain

Location

Fundación Instituto Valenciano de Oncología ( Site 1209)

Valencia, Valenciana, Comunitat, 46009, Spain

Location

Hospital Clinico San Carlos-Oncology Department ( Site 1204)

Madrid, 28040, Spain

Location

Baskent University Dr. Turgut Noyan Research and Training Center ( Site 1303)

Adana, 01250, Turkey (Türkiye)

Location

Hacettepe Universitesi-oncology hospital ( Site 1301)

Ankara, 06230, Turkey (Türkiye)

Location

Ankara City Hospital-Medical Oncology ( Site 1306)

Ankara, 06800, Turkey (Türkiye)

Location

Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 1302)

Istanbul, 34668, Turkey (Türkiye)

Location

TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1305)

Istanbul, 34722, Turkey (Türkiye)

Location

Beatson West of Scotland Cancer Centre-Clinical Trials Unit ( Site 1401)

Glasgow, Glasgow City, G12 0YN, United Kingdom

Location

UCLH-Cancer Clinical Trials Unit ( Site 1402)

London-Camden, London, City of, NW1 2PG, United Kingdom

Location

Velindre Cancer Centre-Research and Development ( Site 1415)

Cardiff, CF14 2TL, United Kingdom

Location

University Hospital Coventry & Warwickshire ( Site 1406)

Coventry, CV2 2DX, United Kingdom

Location

Related Publications (1)

• Andre T, Pietrantonio F, Avallone A, Gumus M, Wyrwicz L, Kim JG, Yalcin S, Kwiatkowski M, Lonardi S, Zolnierek J, Odeleye-Ajakaye A, Leconte P, Fogelman D, Kim TW. KEYSTEP-008: phase II trial of pembrolizumab-based combination in MSI-H/dMMR metastatic colorectal cancer. Future Oncol. 2023 Dec;19(37):2445-2452. doi: 10.2217/fon-2022-1105. Epub 2023 Sep 13.

  PMID: 37701986 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Colorectal Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2021
• First Posted: May 20, 2021
• Study Start: June 25, 2021
• Primary Completion: May 21, 2025
• Study Completion (Estimated): August 13, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

TU (5); HU (6); ES (8); CA (3); GR (4); NL (1); GB (4); CO (7); KR (7); DE (7); GU (5); RU (6); LI (3); IT (3); US (11); PL (6); BE (5); DK (4); FR (6); RO (4)