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)

Colorectal Cancer Clinical Trial

Official title:

A Phase 2, Multicenter, Multi Arm, Study to Evaluate MK-1308A (Co-formulated Quavonlimab (MK-1308)/Pembrolizumab) Versus Other Treatments in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer: (MK-1308A-008)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04895722
• Other study ID #: 1308A-008
• Secondary ID: MK-1308A-0082022
• Status: Recruiting
• Phase: Phase 2
• Start date: June 25, 2021
• Est. completion date: November 18, 2025

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 320
• Est. completion date: November 18, 2025
• Est. primary completion date: October 20, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Microsatellite Instability

Intervention

Biological:
• Pembrolizumab
400 mg or 200 mg pembrolizumab administered via IV infusion.
• Pembrolizumab/Quavonlimab
Co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) fixed-dose combination (FDC) administered via IV infusion.
• Pembrolizumab/Favezelimab
Co-formulated pembrolizumab/favezelimab (200 mg/800 mg) FDC administered via IV infusion
• Pembrolizumab/Vibostolimab
Co-formulated pembrolizumab/vibostolimab (200 mg/200 mg) FDC administered via IV infusion
• MK-4830
800 mg MK-4830 administered via IV infusion

Locations

Country	Name	City	State
Belgium	Cliniques universitaires Saint-Luc-Medical Oncology ( Site 0104)	Brussels	Bruxelles-Capitale, Region De
Belgium	UZ Brussel ( Site 0105)	Brussels	Bruxelles-Capitale, Region De
Belgium	UZ Leuven ( Site 0101)	Leuven	Vlaams-Brabant
Belgium	AZ Delta vzw ( Site 0106)	Roeselare	West-Vlaanderen
Belgium	Université Catholique de Louvain-Namur - Centre Hospitalier -Oncology ( Site 0102)	Yvoir	Namur
Canada	The Moncton Hospital-Oncology ( Site 0307)	Moncton	New Brunswick
Canada	McGill University Health Centre-CIM - Oncology ( Site 0306)	Montréal	Quebec
Canada	Sunnybrook Research Institute - Odette Cancer Centre ( Site 0316)	Toronto	Ontario
Colombia	Clinica de la Costa S.A.S. ( Site 1608)	Barranquilla	Atlantico
Colombia	Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia ( Site 1611)	Bogota	Distrito Capital De Bogota
Colombia	Mediservis del Tolima IPS S.A.S ( Site 1609)	Ibague	Tolima
Colombia	Fundación Colombiana de Cancerología Clínica Vida ( Site 1606)	Medellin	Antioquia
Colombia	Instituto de Cancerología ( Site 1610)	Medellin	Antioquia
Colombia	Oncomédica S.A.S ( Site 1602)	Montería	Cordoba
Colombia	Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 1601)	Valledupar	Cesar
Costa Rica	CIMCA-Hemato-Oncology ( Site 2101)	San José	San Jose
Costa Rica	Hospital Metropolitano - Sede Lindora-Metropolitano Research Institute Sede Lindora ( Site 2102)	Santa Ana	San Jose
Denmark	Aalborg Universitetshospital, Syd ( Site 1903)	Aalborg	Nordjylland
Denmark	Rigshospitalet ( Site 1904)	Copenhagen	Hovedstaden
Denmark	Regionshospitalet Gødstrup ( Site 1901)	Herning	Midtjylland
Denmark	Odense Universitetshospital ( Site 1902)	Odense	Syddanmark
Estonia	North Estonia Medical Centre Foundation-Chemotherapy ( Site 2301)	Tallinn	Harjumaa
Estonia	Tartu University Hospital ( Site 2302)	Tartu	Tartumaa
France	Centre Georges François Leclerc ( Site 0506)	Dijon	Cote-d Or
France	Hopital Claude Huriez - CHU de Lille ( Site 0510)	Lille	Nord
France	Assistance Publique Hôpitaux de Marseille - Hôpital de la Ti-Service d'Hepato-Gastro-Enterologie et	Marseille	Bouches-du-Rhone
France	Hôpital Saint Antoine-Oncologie médicale ( Site 0508)	Paris
France	Centre Hospitalier Universitaire de Poitiers ( Site 0511)	Poitiers	Vienne
France	CHU Rangueil-Digestive oncology department ( Site 0502)	Toulouse	Haute-Garonne
Germany	Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0604)	Berlin
Germany	Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 0601)	Dresden	Sachsen
Germany	Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung ( Site 0611)	Essen	Nordrhein-Westfalen
Germany	Asklepios Altona-Oncology ( Site 0602)	Hamburg
Germany	Otto-von-Guericke-Universität Magdeburg-Klinik für Gastroenterologie, Hepatologie und Infektiologie	Magdeburg	Sachsen-Anhalt
Germany	Universitätsklinikum Marburg ( Site 0610)	Marburg	Hessen
Germany	Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie ( Site 0612)	Muenchen	Bayern
Greece	Alexandra General Hospital of Athens-ONCOLOGY DEPT. ( Site 2704)	Athens	Attiki
Greece	Evgenidion Hospital ( Site 2702)	Athens	Attiki
Greece	University General Hospital of Heraklion-Internal Medicine-Oncology ( Site 2703)	Heraklion	Irakleio
Greece	European Interbalkan Medical Center-Oncology Department ( Site 2701)	Thessaloniki
Guatemala	CELAN,S.A ( Site 2202)	Guatemala
Guatemala	INTEGRA Cancer Institute-Oncology ( Site 2201)	Guatemala
Guatemala	MEDI-K CAYALA ( Site 2205)	Guatemala
Guatemala	Centro Medico Integral De Cancerología (CEMIC) ( Site 2203)	Quetzaltenango
Guatemala	Centro Regional de Sub Especialidades Médicas SA ( Site 2204)	Quetzaltenango
Hungary	Semmelweis Egyetem-Belgyógyászati és Hematológiai Klinika ( Site 2002)	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont-Onkológiai Klinika ( Site 2008)	Debrecen
Hungary	Somogy Megyei Kaposi Mór Oktató Kórház-Oncology center ( Site 2010)	Kaposvár	Somogy
Hungary	Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 2005)	Kecskemét	Bacs-Kiskun
Hungary	Pécsi Tudományegyetem Klinikai Központ-Onkoterápiás Intézet ( Site 2009)	Pécs	Baranya
Hungary	Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Onkologiai Kozpont ( Site 2001)	Szolnok	Jasz-Nagykun-Szolnok
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0802)	Milan	Lombardia
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale-Department of Abdominal Oncology ( Site 0803)	Napoli
Italy	Istituto Oncologico Veneto IRCCS ( Site 0804)	Padova
Korea, Republic of	Kyungpook National University Chilgok Hospital-Hematology/oncology ( Site 1103)	Daegu	Taegu-Kwangyokshi
Korea, Republic of	Asan Medical Center-Department of Oncology ( Site 1105)	Seoul
Korea, Republic of	Korea University Anam Hospital ( Site 1107)	Seoul
Korea, Republic of	Samsung Medical Center-Division of Hematology/Oncology ( Site 1102)	Seoul
Korea, Republic of	Seoul National University Hospital-Internal Medicine ( Site 1101)	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1104)	Seoul
Korea, Republic of	The Catholic Univ. of Korea Seoul St. Mary's Hospital-Medical Oncology ( Site 1106)	Seoul
Lithuania	Hospital of Lithuanian University of Health Sciences Kauno klinikos ( Site 2402)	Kaunas	Kauno Apskritis
Lithuania	National Cancer Institute ( Site 2401)	Vilnius	Vilniaus Miestas
Lithuania	VILNIUS UNIVERSITY HOSPITAL SANTAROS KLINIKOS ( Site 2403)	Vilnius
Netherlands	Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL) ( Site 2901)	Amsterdam	Noord-Holland
Poland	Powiatowe Centrum Zdrowia ( Site 0911)	Brzeziny	Lodzkie
Poland	Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0903)	Koszalin	Zachodniopomorskie
Poland	Mrukmed-Mrukmed ( Site 0901)	Rzeszow	Podkarpackie
Poland	Luxmed Onkologia sp. z o. o. ( Site 0915)	Warszawa	Mazowieckie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Onkologii i Radioterapii ( Site	Warszawa	Mazowieckie
Poland	DOLNOSLASKIE CENTRUM ONKOLOGII PULMONOLOGII I HEMATOLOGII ( Site 0920)	Wroclaw	Dolnoslaskie
Romania	Spitalul de Oncologie Monza Oncologie Medicala ( Site 2601)	Bucharest	Bucuresti
Romania	Fundeni Clinical Institute-Medical Oncology ( Site 2603)	Bucure?ti	Bucuresti
Romania	Cardiomed SRL Cluj-Napoca ( Site 2602)	Cluj-Napoca	Cluj
Romania	Centrul de Oncologie "Sfântul Nectarie"-Medical Oncology ( Site 2604)	Craiova	Dolj
Russian Federation	Republican Clinical Oncology Dispensary-Chemotherapy #3 ( Site 1006)	Kazan	Tatarstan, Respublika
Russian Federation	Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology-Clinical Pharmacology and Chemotherapy	Moscow	Moskva
Russian Federation	First Moscow State Medical University I.M. Sechenov-Interhospital Institution Health Management Cl	Moscow	Moskva
Russian Federation	Rostov Cancer Research Institute ( Site 1014)	Rostov on Don	Rostovskaya Oblast
Russian Federation	Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 1001)	Saint Petersburg	Leningradskaya Oblast
Russian Federation	GBUZ SPb CRPCstmc(o) ( Site 1005)	Sankt- Peterburg	Sankt-Peterburg
Spain	Hospital Universitari Vall d'Hebron ( Site 1201)	Barcelona	Cataluna
Spain	Hospital Clinico San Carlos-Oncology Department ( Site 1204)	Madrid
Spain	HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1206)	Madrid	Madrid, Comunidad De
Spain	H.R.U Malaga - Hospital General ( Site 1207)	Málaga	Malaga
Spain	Hospital Universitario Central de Asturias-Medical Oncology ( Site 1203)	Oviedo	Asturias
Spain	COMPLEJO HOSPITALARIO DE NAVARRA-oncologia médica ( Site 1210)	Pamplona	Navarra
Spain	Hospital Universitario Marqués de Valdecilla ( Site 1202)	Santander	Cantabria
Spain	Fundación Instituto Valenciano de Oncología ( Site 1209)	Valencia	Valenciana, Comunitat
Turkey	Baskent University Dr. Turgut Noyan Research and Training Center ( Site 1303)	Adana
Turkey	Ankara City Hospital-Medical Oncology ( Site 1306)	Ankara
Turkey	Hacettepe Universitesi-oncology hospital ( Site 1301)	Ankara
Turkey	Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 1302)	Istanbul
Turkey	TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1305)	Istanbul
United Kingdom	Velindre Cancer Centre-Research and Development ( Site 1415)	Cardiff
United Kingdom	University Hospital Coventry & Warwickshire ( Site 1406)	Coventry
United Kingdom	Beatson West of Scotland Cancer Centre-Clinical Trials Unit ( Site 1401)	Glasgow	Glasgow City
United Kingdom	UCLH-Cancer Clinical Trials Unit ( Site 1402)	London-Camden	London, City Of
United States	University Cancer & Blood Center, LLC ( Site 1521)	Athens	Georgia
United States	University of Chicago Medical Center-Medicine - Section of Hematology/Oncology - Gastrointestinal P	Chicago	Illinois
United States	UT Southwestern Medical Center ( Site 1551)	Dallas	Texas
United States	The West Clinic, PLLC dba West Cancer Center ( Site 1576)	Germantown	Tennessee
United States	Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 1509)	Nashville	Tennessee
United States	Icahn School of Medicine at Mount Sinai ( Site 1528)	New York	New York
United States	Hematology Oncology Associates of Rockland ( Site 1525)	Nyack	New York
United States	Mid Florida Cancer Center ( Site 1519)	Orange City	Florida
United States	UPMC Hillman Cancer Center ( Site 1516)	Pittsburgh	Pennsylvania
United States	Northwest Medical Specialties, PLLC ( Site 1546)	Tacoma	Washington
United States	Baylor Scott & White Medical Center - Temple-Division of Hematology/Oncology ( Site 1549)	Temple	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Colombia,  Costa Rica,  Denmark,  Estonia,  France,  Germany,  Greece,  Guatemala,  Hungary,  Italy,  Korea, Republic of,  Lithuania,  Netherlands,  Poland,  Romania,  Russian Federation,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 50 months
Secondary	Duration of Response (DOR) per RECIST 1.1 as assessed by BICR	DOR is defined as the time from the first documented evidence of a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until Progressive Disease (PD) or death due to any cause, whichever occurs first, in participants demonstrating a CR or PR. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.	Up to approximately 50 months
Secondary	Progression-Free Survival (PFS) per RECIST 1.1 as assessed by BICR	PFS is defined as the time from randomization (or first dose) to the first documented PD per RECIST 1.1 or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.	Up to approximately 50 months
Secondary	PFS per RECIST 1.1 as assessed by Investigator	PFS is defined as the time from randomization (or first dose) to the first documented PD per RECIST 1.1 or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by investigator will be presented.	Up to approximately 50 months
Secondary	ORR per RECIST 1.1 as assessed by Investigator	ORR is defined as the percentage of participants who have a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR as assessed by investigator will be presented.	Up to approximately 50 months
Secondary	DOR per RECIST 1.1 as assessed by Investigator	DOR is defined as the time from the first documented evidence of a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until PD or death due to any cause, whichever occurs first, in participants demonstrating a CR or PR. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by investigator will be presented.	Up to approximately 50 months
Secondary	Overall Survival (OS)	OS is defined as the time from randomization (or first dose) to death due to any cause. OS will be presented.	Up to approximately 50 months
Secondary	Number of Participants Who Experienced an Adverse Event (AE)	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study intervention. The number of participants with an AE will be presented.	Up to approximately 50 months
Secondary	Number of Participants Discontinuing Study Treatment Due to an AE	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study intervention. The number of participants that discontinue study treatment due to an AE will be presented.	Up to approximately 50 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary