Safety and Efficacy of Pembrolizumab Compared to Placebo in Resected High-risk Stage II Melanoma (MK-3475-716/KEYNOTE-716)
- Registration Number
- NCT03553836
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This 2-part study will evaluate the safety and efficacy of pembrolizumab (MK-3475) compared to placebo in participants with surgically resected high-risk Stage II melanoma. Participants in Part 1 will receive either pembrolizumab or placebo in a double-blind design every 3 weeks (Q3W) for up to 17 cycles/\~1 year (each cycle = 21 days). Participants who complete the initial treatment of 17 cycles of pembrolizumab in Part 1 and experience disease recurrence may be eligible for re-challenge with pembrolizumab at the same dose and schedule of 200 mg Q3W (21-day cycles) for up to 35 cycles (up to \~2 years) in Part 2 in an open label design. Participants who complete the initial treatment of placebo and experience disease recurrence may be eligible to switch over to pembrolizumab 200 mg Q3W (21-day cycles) for up to 35 cycles (up to \~2 years) in Part 2 in an open label design. The primary hypothesis of this study is that pembrolizumab increases recurrence-free survival (RFS) compared to placebo.
Per protocol, response/ progression or adverse events (AEs) during re-challenge/switch-over in Part 2 will not be counted towards the RFS outcome measure or safety outcome measures respectively.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 976
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab Pembrolizumab Participants receive 200 mg pembrolizumab (2 mg/kg for a maximum of 200 mg in pediatric participants) by intravenous (IV) infusion once every 3 weeks (Q3W; 21-day cycles) for up to 17 cycles (up to \~1 year) in Part 1. Participants who complete the initial treatment of 17 cycles of pembrolizumab and experience disease recurrence may be eligible for re-challenge with pembrolizumab at the same dose and schedule of 200 mg Q3W (21-day cycles) for up to 35 cycles (up to \~2 years) in Part 2. Placebo Pembrolizumab Participants receive saline placebo by IV infusion Q3W (21-day cycles) for up to 17 cycles (up to \~1 year) in Part 1. Participants who complete the initial treatment of 17 cycles of placebo and experience disease recurrence may be eligible to switch over to pembrolizumab 200 mg Q3W (21-day cycles) for up to 35 cycles (up to \~2 years) in Part 2. Placebo Placebo Participants receive saline placebo by IV infusion Q3W (21-day cycles) for up to 17 cycles (up to \~1 year) in Part 1. Participants who complete the initial treatment of 17 cycles of placebo and experience disease recurrence may be eligible to switch over to pembrolizumab 200 mg Q3W (21-day cycles) for up to 35 cycles (up to \~2 years) in Part 2.
- Primary Outcome Measures
Name Time Method Recurrence-free Survival (RFS) Up to ~32.7 months RFS was defined as the time from randomization to any of the following events: recurrence of melanoma at any site (local, in-transit or regional lymph nodes or distant recurrence) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first. Per protocol, final analysis for this primary outcome measure was performed using the initial pembrolizumab or placebo treatment with a protocol-specified analysis data cut-off date of June-21-2021.
- Secondary Outcome Measures
Name Time Method Distant Metastasis-free Survival (DMFS) Up to ~9 years DMFS will be defined as the time from randomization to the first diagnosis of a distant metastasis per RECIST 1.1. Distant metastasis will refer to cancer that has spread from the original (primary) tumor and beyond local tissues and lymph nodes to distant organs or distant lymph nodes. DMFS will be reported for randomized participants.
Number of Participants Who Experienced at Least One Adverse Event (AE) Up to ~19.3 months An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, analysis for this outcome measure was performed using the initial pembrolizumab or placebo treatment.
Overall Survival (OS) Up to ~15 years OS will be defined as the time from randomization to death due to any cause. OS will be reported for randomized participants.
Number of Participants Who Discontinued Study Treatment Due to an AE Up to ~19.3 months An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, analysis for this outcome measure was performed using the initial pembrolizumab or placebo treatment.
Trial Locations
- Locations (159)
The Angeles Clinic and Research Institute ( Site 0029)
🇺🇸Los Angeles, California, United States
Winship Cancer Institute of Emory University ( Site 0046)
🇺🇸Atlanta, Georgia, United States
UCLA Hematology & Oncology ( Site 0130)
🇺🇸Los Angeles, California, United States
UPMC Hillman Cancer Centers ( Site 0043)
🇺🇸Pittsburgh, Pennsylvania, United States
University of Arizona Cancer Center ( Site 0121)
🇺🇸Tucson, Arizona, United States
UCSD Moores Cancer Center ( Site 0133)
🇺🇸La Jolla, California, United States
John Wayne Cancer Institute ( Site 0026)
🇺🇸Santa Monica, California, United States
Mayo Clinic Florida ( Site 0024)
🇺🇸Jacksonville, Florida, United States
Northwestern Medical Group ( Site 0135)
🇺🇸Chicago, Illinois, United States
Northside Hospital ( Site 0115)
🇺🇸Atlanta, Georgia, United States
The University of Chicago Medical Center ( Site 0007)
🇺🇸Chicago, Illinois, United States
Advocate Medical Group-Park Ridge ( Site 0025)
🇺🇸Park Ridge, Illinois, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 0047)
🇺🇸Baltimore, Maryland, United States
University of Iowa Hospital and Clinics ( Site 0001)
🇺🇸Iowa City, Iowa, United States
Massachusetts General Hospital ( Site 0126)
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute ( Site 0124)
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center ( Site 0141)
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering ( Site 0006)
🇺🇸Harrison, New York, United States
Laura and Isaac Perlmutter Cancer Center ( Site 0137)
🇺🇸New York, New York, United States
Mount Sinai Medical Center ( Site 0038)
🇺🇸New York, New York, United States
Siteman Cancer Center ( Site 0143)
🇺🇸Saint Louis, Missouri, United States
University of Rochester ( Site 0019)
🇺🇸Rochester, New York, United States
Memorial Sloan Kettering Cancer Center ( Site 0142)
🇺🇸New York, New York, United States
Oregon Health & Science University ( Site 0032)
🇺🇸Portland, Oregon, United States
Children's Hospital of Pittsburgh UPMC ( Site 0144)
🇺🇸Pittsburgh, Pennsylvania, United States
West Cancer Center - East Campus ( Site 0022)
🇺🇸Germantown, Tennessee, United States
University of Tennessee Medical Center Knoxville ( Site 0116)
🇺🇸Knoxville, Tennessee, United States
University of Texas-MD Anderson Cancer Center ( Site 0134)
🇺🇸Houston, Texas, United States
Inova Schar Cancer Institute ( Site 0014)
🇺🇸Fairfax, Virginia, United States
Seattle Cancer Care Alliance ( Site 0044)
🇺🇸Seattle, Washington, United States
Melanoma Institute Australia ( Site 0856)
🇦🇺North Sydney, New South Wales, Australia
VCU Massey Cancer Center ( Site 0008)
🇺🇸Richmond, Virginia, United States
University of Wisconsin Hospital and Clinics ( Site 0030)
🇺🇸Madison, Wisconsin, United States
Westmead Hospital ( Site 0853)
🇦🇺Westmead, New South Wales, Australia
Cairns Base Hospital ( Site 0859)
🇦🇺Cairns, Queensland, Australia
Tasman Oncology Research Pty Ltd ( Site 0858)
🇦🇺Southport, Queensland, Australia
Princess Alexandra Hospital ( Site 0857)
🇦🇺Woolloongabba, Queensland, Australia
Royal Adelaide Hospital ( Site 0861)
🇦🇺Adelaide, South Australia, Australia
Ashford Cancer Centre Research ( Site 0860)
🇦🇺Kurralta Park, South Australia, Australia
GZA Sint Augustinus ( Site 0259)
🇧🇪Wilrijk - Antwerpen, Antwerpen, Belgium
The Alfred Hospital ( Site 0852)
🇦🇺Melbourne, Victoria, Australia
Cliniques Universitaires Saint-Luc ( Site 0251)
🇧🇪Brussels, Bruxelles-Capitale, Region De, Belgium
Institut Jules Bordet ( Site 0254)
🇧🇪Bruxelles, Bruxelles-Capitale, Region De, Belgium
UZ Gent ( Site 0255)
🇧🇪Gent, Oost-Vlaanderen, Belgium
UZ Leuven ( Site 0252)
🇧🇪Leuven, Vlaams-Brabant, Belgium
Hospital Erasto Gaertner ( Site 0159)
🇧🇷Curitiba, Parana, Brazil
Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 0155)
🇧🇷Barretos, Sao Paulo, Brazil
Hospital de Clinicas de Rio Preto ( Site 0162)
🇧🇷Sao Jose Do Rio Preto - SP, Sao Paulo, Brazil
Instituto Nacional do Cancer II ( Site 0160)
🇧🇷Rio de Janeiro, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0151)
🇧🇷Sao Paulo, Brazil
A.C. Camargo Cancer Center ( Site 0164)
🇧🇷Sao Paulo, Brazil
Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 0161)
🇧🇷Sao Paulo, Brazil
Cross Cancer Institute ( Site 0057)
🇨🇦Edmonton, Alberta, Canada
CancerCare Manitoba ( Site 0053)
🇨🇦Winnipeg, Manitoba, Canada
The Ottawa Hospital ( Site 0058)
🇨🇦Ottawa, Ontario, Canada
Moncton Hospital - Horizon Health Network ( Site 0055)
🇨🇦Moncton, New Brunswick, Canada
Sunnybrook Research Institute ( Site 0060)
🇨🇦Toronto, Ontario, Canada
Princess Margaret Cancer Centre ( Site 0059)
🇨🇦Toronto, Ontario, Canada
Hopital Maisonneuve Rosemont ( Site 0056)
🇨🇦Montreal, Quebec, Canada
Jewish General Hospital ( Site 0054)
🇨🇦Montreal, Quebec, Canada
McGill University Health Centre ( Site 0062)
🇨🇦Montreal, Quebec, Canada
Instituto Clinico Oncologico del Sur ( Site 0203)
🇨🇱Temuco, Araucania, Chile
CHU de Quebec - Hotel-Dieu de Quebec ( Site 0061)
🇨🇦Quebec, Canada
Pontificia Universidad Catolica de Chile ( Site 0201)
🇨🇱Santiago, Region M. De Santiago, Chile
Hopital La Timone ( Site 0302)
🇫🇷Marseille, Bouches-du-Rhone, France
CHU Dijon Bourgogne ( Site 0320)
🇫🇷Dijon, Cote-d Or, France
Institut Claudius Regaud IUCT Oncopole ( Site 0306)
🇫🇷Toulouse, Haute-Garonne, France
CHU Montpellier. ( Site 0312)
🇫🇷Montpellier, Herault, France
Hopital Ambroise Pare Boulogne ( Site 0316)
🇫🇷Boulogne-Billancourt, Hauts-de-Seine, France
CHU Angers ( Site 0321)
🇫🇷Angers, Maine-et-Loire, France
CHU Amiens Picardie Hopital Nord ( Site 0317)
🇫🇷Amiens, Somme, France
C.H.U. Lyon Sud ( Site 0303)
🇫🇷Pierre Benite, Rhone, France
Hopital Saint Louis ( Site 0322)
🇫🇷Paris, France
Universitaetsklinikum in Mannheim ( Site 0351)
🇩🇪Mannheim, Baden-Wurttemberg, Germany
Universitaetsklinikum Tuebingen ( Site 0353)
🇩🇪Tuebingen, Baden-Wurttemberg, Germany
Elbe Klinikum Buxtehude ( Site 0354)
🇩🇪Buxtehude, Niedersachsen, Germany
Klinikum der Universitaet in Wuerzburg ( Site 0356)
🇩🇪Wuerzburg, Bayern, Germany
Klinikum der Ludwig-Maximilians-Universitaet Muenchen ( Site 0357)
🇩🇪Muenchen, Bayern, Germany
Medizinische Hochschule Hannover ( Site 0358)
🇩🇪Hannover, Niedersachsen, Germany
Klinik und Poliklinik fuer Dermatologie Venerologie und Allergologie ( Site 0361)
🇩🇪Essen, Nordrhein-Westfalen, Germany
SRH Wald-Klinikum Gera GmbH ( Site 0360)
🇩🇪Gera, Thuringen, Germany
Universitaetsklinikum Hamburg Eppendorf (UKE) ( Site 0352)
🇩🇪Hamburg, Germany
Soroka Medical Center ( Site 0653)
🇮🇱Beer Sheva, Southern, Israel
Sourasky Medical Center ( Site 0656)
🇮🇱Tel Aviv, Tell Abib, Israel
HaEmek Medical Center ( Site 0655)
🇮🇱Afula, Israel
Hadassah Ein Kerem Medical Center ( Site 0651)
🇮🇱Jerusalem, Israel
Chaim Sheba Medical Center. ( Site 0652)
🇮🇱Ramat Gan, Israel
Shamir Medical Center-Assaf Harofeh ( Site 0657)
🇮🇱Zerifin, Israel
Rambam Medical Center ( Site 0654)
🇮🇱Haifa, Israel
IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 0406)
🇮🇹Bari, Italy
Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 0403)
🇮🇹Meldola, Forli-Cesena, Italy
ASST Papa Giovanni XXIII ( Site 0402)
🇮🇹Bergamo, Italy
IRCCS A.O.U. San Martino - IST ( Site 0404)
🇮🇹Genova, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0408)
🇮🇹Milano, Italy
Istituto Nazionale Tumori Fondazione Pascale ( Site 0400)
🇮🇹Napoli, Italy
IRCCS Istituto Oncologico Veneto ( Site 0407)
🇮🇹Padova, Italy
IDI - Istituto Dermopatico dell'Immacolata ( Site 0405)
🇮🇹Roma, Italy
Azienda Ospedaliero Universitaria Senese ( Site 0401)
🇮🇹Siena, Italy
National Cancer Center Hospital ( Site 0910)
🇯🇵Tokyo, Japan
Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0769)
🇵🇱Bydgoszcz, Kujawsko-pomorskie, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0751)
🇵🇱Warszawa, Mazowieckie, Poland
Kliniczny Szpital Wojewodzki Nr 1 ( Site 0758)
🇵🇱Rzeszow, Podkarpackie, Poland
Pratia MCM Krakow ( Site 0773)
🇵🇱Krakow, Malopolskie, Poland
Instytut Pomnik Centrum Zdrowia Dziecka ( Site 0759)
🇵🇱Warszawa, Mazowieckie, Poland
Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 0754)
🇵🇱Bielsko-Biala, Slaskie, Poland
Uniwersyteckie Centrum Kliniczne ( Site 0770)
🇵🇱Gdansk, Pomorskie, Poland
Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 0753)
🇵🇱Poznan, Wielkopolskie, Poland
Uniwersyteckie Centrum Kliniczne Slaskiego Uniwersytetu Medycznego ( Site 0757)
🇵🇱Katowice, Slaskie, Poland
LIFTMED ( Site 0765)
🇵🇱Rybnik, Slaskie, Poland
Cancer Care Langenhoven Drive Oncology Centre ( Site 0812)
🇿🇦Port Elizabeth, Eastern Cape, South Africa
Sandton Oncology Medical Group PTY LTD ( Site 0801)
🇿🇦Johannesburg, Gauteng, South Africa
Charlotte Maxeke Johannesburg Academic Hospital ( Site 0811)
🇿🇦Parktown, Gauteng, South Africa
MPOC ( Site 0803)
🇿🇦Pretoria, Gauteng, South Africa
Wilgers Oncology Centre ( Site 0806)
🇿🇦Pretoria, Gauteng, South Africa
Cancercare ( Site 0810)
🇿🇦Cape Town, Limpopo, South Africa
Onkologikoa - Instituto Oncologico de San Sebastian ( Site 0457)
🇪🇸San Sebastian, Gipuzkoa, Spain
Cape Town Oncology Trials Pty Ltd ( Site 0807)
🇿🇦Kraaifontein, Western Cape, South Africa
Hospital General Universitario de Valencia ( Site 0451)
🇪🇸Valencia, Valenciana, Comunitat, Spain
Hospital General Universitario Gregorio Maranon ( Site 0454)
🇪🇸Madrid, Spain
Hospital General Universitari Vall d Hebron ( Site 0456)
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona ( Site 0452)
🇪🇸Barcelona, Spain
Hospital Universitario Virgen Macarena ( Site 0455)
🇪🇸Sevilla, Spain
Hopitaux Universitaires de Geneve HUG ( Site 0556)
🇨ðŸ‡Geneva, Geneve, Switzerland
Universitaetsspital Bern ( Site 0552)
🇨ðŸ‡Bern, Berne, Switzerland
Universitaetsspital Basel ( Site 0554)
🇨ðŸ‡Basel, Basel-Stadt, Switzerland
Kantonsspital St. Gallen ( Site 0559)
🇨ðŸ‡St. Gallen, Sankt Gallen, Switzerland
Kantonsspital Graubuenden ( Site 0555)
🇨ðŸ‡Chur, Grisons, Switzerland
Oncological Institute of Southern Switzerland ( Site 0557)
🇨ðŸ‡Bellinzona, Ticino, Switzerland
Centre Hospitalier Universitaire Vaudois ( Site 0553)
🇨ðŸ‡Lausanne, Vaud, Switzerland
Hopital du Valais ( Site 0558)
🇨ðŸ‡Sion, Wallis, Switzerland
Universitaetsspital Zuerich ( Site 0551)
🇨ðŸ‡Zuerich, Zurich, Switzerland
Addenbrooke's Hospital in Cambridge ( Site 0600)
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Guy s & St Thomas NHS Foundation Trust ( Site 0601)
🇬🇧London, London, City Of, United Kingdom
Royal Marsden Hospital - Fulham Road London ( Site 0613)
🇬🇧London, London, City Of, United Kingdom
Christie NHS Foundation Trust ( Site 0604)
🇬🇧Manchester, United Kingdom
The Royal Marsden NHS Foundation Trust. ( Site 0612)
🇬🇧Sutton, Surrey, United Kingdom
Hospital Sao Vicente de Paulo ( Site 0158)
🇧🇷Passo Fundo, Rio Grande Do Sul, Brazil
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0154)
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Universitaetsklinikum Schleswig-Holstein Campus Kiel ( Site 0359)
🇩🇪Kiel, Schleswig-Holstein, Germany
Fiona Stanley Hospital ( Site 0851)
🇦🇺Murdoch, Western Australia, Australia
Hospital de Caridade de Ijui ( Site 0156)
🇧🇷Ijui, Rio Grande Do Sul, Brazil
Sociedad Medica Aren y Bachero Limitada ( Site 0207)
🇨🇱Santiago, Region M. De Santiago, Chile
Centre Eugene Marquis ( Site 0305)
🇫🇷Rennes, Ille-et-Vilaine, France
Oncocentro ( Site 0204)
🇨🇱Vina del Mar, Valparaiso, Chile
Institut Gustave Roussy ( Site 0300)
🇫🇷Villejuif, Val-de-Marne, France
CHU de Bordeaux- Hopital Saint Andre ( Site 0304)
🇫🇷Bordeaux, Gironde, France
Jessa Ziekenhuis Campus Virga Jesse ( Site 0256)
🇧🇪Hasselt, Limburg, Belgium
CHRU Lille - Hopital Claude Huriez ( Site 0301)
🇫🇷Lille, Nord, France
Fundacion Arturo Lopez Perez FALP ( Site 0200)
🇨🇱Santiago, Region M. De Santiago, Chile
CHU de Reims ( Site 0307)
🇫🇷Reims, Marne, France
Centro Oncologico Antofagasta ( Site 0206)
🇨🇱Antofagasta, Chile
The Lindner Center for Research and Education at The Christ Hospital ( Site 0004)
🇺🇸Cincinnati, Ohio, United States
Stephenson Cancer Center ( Site 0042)
🇺🇸Oklahoma City, Oklahoma, United States
Karmanos Cancer Institute ( Site 0111)
🇺🇸Detroit, Michigan, United States
Klinikum Nuernberg Nord ( Site 0355)
🇩🇪Nuernberg, Bayern, Germany
University of Colorado Cancer Center ( Site 0027)
🇺🇸Aurora, Colorado, United States
Yale University ( Site 0035)
🇺🇸New Haven, Connecticut, United States
Moffitt McKinley Outpatient Center ( Site 0131)
🇺🇸Tampa, Florida, United States
Mayo Clinic [Rochester, MN] ( Site 0016)
🇺🇸Rochester, Minnesota, United States