Clinical trial NCT04895722: 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)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-05-20
Enrollment: 302
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 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

Primary outcomes:
measure: 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)
timeFrame: Up to approximately 50 months
Secondary outcomes:
measure: Duration of Response (DOR) per RECIST 1.1 as assessed by BICR
timeFrame: Up to approximately 50 months
measure: Progression-Free Survival (PFS) per RECIST 1.1 as assessed by BICR
timeFrame: Up to approximately 50 months
measure: PFS per RECIST 1.1 as assessed by Investigator
timeFrame: Up to approximately 50 months
measure: ORR per RECIST 1.1 as assessed by Investigator
timeFrame: Up to approximately 50 months
measure: DOR per RECIST 1.1 as assessed by Investigator
timeFrame: Up to approximately 50 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 50 months
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 50 months
measure: Number of Participants Discontinuing Study Treatment Due to an AE
timeFrame: Up to approximately 50 months
Other outcomes:
Locations:
city: Orange City
country: United States
facility: Mid Florida Cancer Center ( Site 1519)
state: Florida
city: Athens
country: United States
facility: University Cancer & Blood Center, LLC ( Site 1521)
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center-Medicine - Section of Hematology/Oncology - Gastrointestinal P
state: Illinois
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai ( Site 1528)
state: New York
city: Nyack
country: United States
facility: Hematology Oncology Associates of Rockland ( Site 1525)
state: New York
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center ( Site 1516)
state: Pennsylvania
city: Germantown
country: United States
facility: The West Clinic, PLLC dba West Cancer Center ( Site 1576)
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 1509)
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center ( Site 1551)
state: Texas
city: Temple
country: United States
facility: Baylor Scott & White Medical Center - Temple-Division of Hematology/Oncology ( Site 1549)
state: Texas
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC ( Site 1546)
state: Washington
city: Brussels
country: Belgium
facility: UZ Brussel ( Site 0105)
state: Bruxelles-Capitale, Region De
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc-Medical Oncology ( Site 0104)
state: Bruxelles-Capitale, Region De
city: Yvoir
country: Belgium
facility: Université Catholique de Louvain-Namur - Centre Hospitalier -Oncology ( Site 0102)
state: Namur
city: Leuven
country: Belgium
facility: UZ Leuven ( Site 0101)
state: Vlaams-Brabant
city: Roeselare
country: Belgium
facility: AZ Delta vzw ( Site 0106)
state: West-Vlaanderen
city: Moncton
country: Canada
facility: The Moncton Hospital-Oncology ( Site 0307)
state: New Brunswick
city: Toronto
country: Canada
facility: Sunnybrook Research Institute - Odette Cancer Centre ( Site 0316)
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Centre-CIM - Oncology ( Site 0306)
state: Quebec
city: Medellin
country: Colombia
facility: Instituto de Cancerología ( Site 1610)
state: Antioquia
city: Medellin
country: Colombia
facility: Fundación Colombiana de Cancerología Clínica Vida ( Site 1606)
state: Antioquia
city: Barranquilla
country: Colombia
facility: Clinica de la Costa S.A.S. ( Site 1608)
state: Atlantico
city: Valledupar
country: Colombia
facility: Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 1601)
state: Cesar
city: Montería
country: Colombia
facility: Oncomédica S.A.S ( Site 1602)
state: Cordoba
city: Bogota
country: Colombia
facility: Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia ( Site 1611)
state: Distrito Capital De Bogota
city: Ibague
country: Colombia
facility: Mediservis del Tolima IPS S.A.S ( Site 1609)
state: Tolima
city: San José
country: Costa Rica
facility: CIMCA-Hemato-Oncology ( Site 2101)
state: San Jose
city: Santa Ana
country: Costa Rica
facility: Hospital Metropolitano - Sede Lindora-Metropolitano Research Institute Sede Lindora ( Site 2102)
state: San Jose
city: Copenhagen
country: Denmark
facility: Rigshospitalet ( Site 1904)
state: Hovedstaden
city: Herning
country: Denmark
facility: Regionshospitalet Gødstrup ( Site 1901)
state: Midtjylland
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital, Syd ( Site 1903)
state: Nordjylland
city: Odense
country: Denmark
facility: Odense Universitetshospital ( Site 1902)
state: Syddanmark
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre Foundation-Chemotherapy ( Site 2301)
state: Harjumaa
city: Tartu
country: Estonia
facility: Tartu University Hospital ( Site 2302)
state: Tartumaa
city: Marseille
country: France
facility: Assistance Publique Hôpitaux de Marseille - Hôpital de la Ti-Service d'Hepato-Gastro-Enterologie et
state: Bouches-du-Rhone
city: Dijon
country: France
facility: Centre Georges François Leclerc ( Site 0506)
state: Cote-d Or
city: Toulouse
country: France
facility: CHU Rangueil-Digestive oncology department ( Site 0502)
state: Haute-Garonne
city: Lille
country: France
facility: Hopital Claude Huriez - CHU de Lille ( Site 0510)
state: Nord
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers ( Site 0511)
state: Vienne
city: Paris
country: France
facility: Hôpital Saint Antoine-Oncologie médicale ( Site 0508)
city: Muenchen
country: Germany
facility: Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie ( Site 0612)
state: Bayern
city: Marburg
country: Germany
facility: Universitätsklinikum Marburg ( Site 0610)
state: Hessen
city: Essen
country: Germany
facility: Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung ( Site 0611)
state: Nordrhein-Westfalen
city: Magdeburg
country: Germany
facility: Otto-von-Guericke-Universität Magdeburg-Klinik für Gastroenterologie, Hepatologie und Infektiologie
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 0601)
state: Sachsen
city: Berlin
country: Germany
facility: Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0604)
city: Hamburg
country: Germany
facility: Asklepios Altona-Oncology ( Site 0602)
city: Athens
country: Greece
facility: Alexandra General Hospital of Athens-ONCOLOGY DEPT. ( Site 2704)
state: Attiki
city: Athens
country: Greece
facility: Evgenidion Hospital ( Site 2702)
state: Attiki
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion-Internal Medicine-Oncology ( Site 2703)
state: Irakleio
city: Thessaloniki
country: Greece
facility: European Interbalkan Medical Center-Oncology Department ( Site 2701)
city: Guatemala
country: Guatemala
facility: CELAN,S.A ( Site 2202)
city: Guatemala
country: Guatemala
facility: INTEGRA Cancer Institute-Oncology ( Site 2201)
city: Guatemala
country: Guatemala
facility: MEDI-K CAYALA ( Site 2205)
city: Quetzaltenango
country: Guatemala
facility: Centro Regional de Sub Especialidades Médicas SA ( Site 2204)
city: Quetzaltenango
country: Guatemala
facility: Centro Medico Integral De Cancerología (CEMIC) ( Site 2203)
city: Kecskemét
country: Hungary
facility: Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 2005)
state: Bacs-Kiskun
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem Klinikai Központ-Onkoterápiás Intézet ( Site 2009)
state: Baranya
city: Szolnok
country: Hungary
facility: Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Onkologiai Kozpont ( Site 2001)
state: Jasz-Nagykun-Szolnok
city: Kaposvár
country: Hungary
facility: Somogy Megyei Kaposi Mór Oktató Kórház-Oncology center ( Site 2010)
state: Somogy
city: Budapest
country: Hungary
facility: Semmelweis Egyetem-Belgyógyászati és Hematológiai Klinika ( Site 2002)
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont-Onkológiai Klinika ( Site 2008)
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0802)
state: Lombardia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale-Department of Abdominal Oncology ( Site 0803)
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS ( Site 0804)
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital-Hematology/oncology ( Site 1103)
state: Taegu-Kwangyokshi
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital ( Site 1107)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital-Internal Medicine ( Site 1101)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1104)
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center-Department of Oncology ( Site 1105)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center-Division of Hematology/Oncology ( Site 1102)
city: Seoul
country: Korea, Republic of
facility: The Catholic Univ. of Korea Seoul St. Mary's Hospital-Medical Oncology ( Site 1106)
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kauno klinikos ( Site 2402)
state: Kauno Apskritis
city: Vilnius
country: Lithuania
facility: National Cancer Institute ( Site 2401)
state: Vilniaus Miestas
city: Vilnius
country: Lithuania
facility: VILNIUS UNIVERSITY HOSPITAL SANTAROS KLINIKOS ( Site 2403)
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL) ( Site 2901)
state: Noord-Holland
city: Wroclaw
country: Poland
facility: DOLNOSLASKIE CENTRUM ONKOLOGII PULMONOLOGII I HEMATOLOGII ( Site 0920)
state: Dolnoslaskie
city: Brzeziny
country: Poland
facility: Powiatowe Centrum Zdrowia ( Site 0911)
state: Lodzkie
city: Warszawa
country: Poland
facility: Luxmed Onkologia sp. z o. o. ( Site 0915)
state: Mazowieckie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Onkologii i Radioterapii ( Site
state: Mazowieckie
city: Rzeszow
country: Poland
facility: Mrukmed-Mrukmed ( Site 0901)
state: Podkarpackie
city: Koszalin
country: Poland
facility: Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0903)
state: Zachodniopomorskie
city: Bucharest
country: Romania
facility: Spitalul de Oncologie Monza Oncologie Medicala ( Site 2601)
state: Bucuresti
city: București
country: Romania
facility: Fundeni Clinical Institute-Medical Oncology ( Site 2603)
state: Bucuresti
city: Cluj-Napoca
country: Romania
facility: Cardiomed SRL Cluj-Napoca ( Site 2602)
state: Cluj
city: Craiova
country: Romania
facility: Centrul de Oncologie "Sfântul Nectarie"-Medical Oncology ( Site 2604)
state: Dolj
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 1001)
state: Leningradskaya Oblast
city: Moscow
country: Russian Federation
facility: Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology-Clinical Pharmacology and Chemotherapy
state: Moskva
city: Moscow
country: Russian Federation
facility: First Moscow State Medical University I.M. Sechenov-Interhospital Institution Health Management Cl
state: Moskva
city: Rostov on Don
country: Russian Federation
facility: Rostov Cancer Research Institute ( Site 1014)
state: Rostovskaya Oblast
city: Sankt- Peterburg
country: Russian Federation
facility: GBUZ SPb CRPCstmc(o) ( Site 1005)
state: Sankt-Peterburg
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncology Dispensary-Chemotherapy #3 ( Site 1006)
state: Tatarstan, Respublika
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias-Medical Oncology ( Site 1203)
state: Asturias
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla ( Site 1202)
state: Cantabria
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron ( Site 1201)
state: Cataluna
city: Madrid
country: Spain
facility: HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1206)
state: Madrid, Comunidad De
city: Málaga
country: Spain
facility: H.R.U Malaga - Hospital General ( Site 1207)
state: Malaga
city: Pamplona
country: Spain
facility: COMPLEJO HOSPITALARIO DE NAVARRA-oncologia médica ( Site 1210)
state: Navarra
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano de Oncología ( Site 1209)
state: Valenciana, Comunitat
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos-Oncology Department ( Site 1204)
city: Adana
country: Turkey
facility: Baskent University Dr. Turgut Noyan Research and Training Center ( Site 1303)
city: Ankara
country: Turkey
facility: Hacettepe Universitesi-oncology hospital ( Site 1301)
city: Ankara
country: Turkey
facility: Ankara City Hospital-Medical Oncology ( Site 1306)
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 1302)
city: Istanbul
country: Turkey
facility: TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1305)
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre-Clinical Trials Unit ( Site 1401)
state: Glasgow City
city: London-Camden
country: United Kingdom
facility: UCLH-Cancer Clinical Trials Unit ( Site 1402)
state: London, City Of
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre-Research and Development ( Site 1415)
city: Coventry
country: United Kingdom
facility: University Hospital Coventry & Warwickshire ( Site 1406)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: