Safety and Efficacy of Pembrolizumab Compared to Placebo in Resected High-risk Stage II Melanoma (MK-3475-716/KEYNOTE-716)

Adjuvant Therapy With Pembrolizumab Versus Placebo in Resected High-risk Stage II Melanoma: A Randomized, Double-blind Phase 3 Study (KEYNOTE-716)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma
• Intervention / Treatment: Biological: Pembrolizumab; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 976
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • North Sydney, New South Wales, Australia, 2065
      • Melanoma Institute Australia ( Site 0856)
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital ( Site 0853)
  • Queensland
    • Cairns, Queensland, Australia, 4870
      • Cairns Base Hospital ( Site 0859)
    • Southport, Queensland, Australia, 4215
      • Tasman Oncology Research Pty Ltd ( Site 0858)
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital ( Site 0857)
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital ( Site 0861)
    • Kurralta Park, South Australia, Australia, 5037
      • Ashford Cancer Centre Research ( Site 0860)
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital ( Site 0852)
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital ( Site 0851)
• Belgium
  • Antwerpen
    • Wilrijk - Antwerpen, Antwerpen, Belgium, 2610
      • GZA Sint Augustinus ( Site 0259)
  • Bruxelles-Capitale, Region De
    • Brussels, Bruxelles-Capitale, Region De, Belgium, 1200
      • Cliniques Universitaires Saint-Luc ( Site 0251)
    • Bruxelles, Bruxelles-Capitale, Region De, Belgium, 1000
      • Institut Jules Bordet ( Site 0254)
  • Limburg
    • Hasselt, Limburg, Belgium, 3500
      • Jessa Ziekenhuis Campus Virga Jesse ( Site 0256)
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent ( Site 0255)
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • UZ Leuven ( Site 0252)
• Brazil
  • Rio de Janeiro, Brazil, 20220-410
    • Instituto Nacional do Cancer II ( Site 0160)
  • Sao Paulo, Brazil, 01246-000
    • Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0151)
  • Sao Paulo, Brazil, 01321-001
    • Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 0161)
  • Sao Paulo, Brazil, 01508-010
    • A.C. Camargo Cancer Center ( Site 0164)
  • Parana
    • Curitiba, Parana, Brazil, 81520-060
      • Hospital Erasto Gaertner ( Site 0159)
  • Rio Grande Do Sul
    • Ijui, Rio Grande Do Sul, Brazil, 98700 000
      • Hospital de Caridade de Ijui ( Site 0156)
    • Passo Fundo, Rio Grande Do Sul, Brazil, 99010-080
      • Hospital Sao Vicente de Paulo ( Site 0158)
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
      • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0154)
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14784-400
      • Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 0155)
    • Sao Jose Do Rio Preto - SP, Sao Paulo, Brazil, 15090-000
      • Hospital de Clinicas de Rio Preto ( Site 0162)
• Canada
  • Quebec, Canada, G1R 2J6
    • CHU de Quebec - Hotel-Dieu de Quebec ( Site 0061)
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute ( Site 0057)
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba ( Site 0053)
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Moncton Hospital - Horizon Health Network ( Site 0055)
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital ( Site 0058)
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Research Institute ( Site 0060)
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre ( Site 0059)
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Hopital Maisonneuve Rosemont ( Site 0056)
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital ( Site 0054)
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre ( Site 0062)
• Chile
  • Antofagasta, Chile, 1240000
    • Centro Oncologico Antofagasta ( Site 0206)
  • Araucania
    • Temuco, Araucania, Chile, 4810469
      • Instituto Clinico Oncologico del Sur ( Site 0203)
  • Region M. De Santiago
    • Santiago, Region M. De Santiago, Chile, 7500921
      • Fundacion Arturo Lopez Perez FALP ( Site 0200)
    • Santiago, Region M. De Santiago, Chile, 8330032
      • Pontificia Universidad Catolica de Chile ( Site 0201)
    • Santiago, Region M. De Santiago, Chile, 8420383
      • Sociedad Medica Aren y Bachero Limitada ( Site 0207)
  • Valparaiso
    • Vina del Mar, Valparaiso, Chile, 2520598
      • Oncocentro ( Site 0204)
• France
  • Paris, France, 75475
    • Hopital Saint Louis ( Site 0322)
  • Bouches-du-Rhone
    • Marseille, Bouches-du-Rhone, France, 13385
      • Hopital La Timone ( Site 0302)
  • Cote-d Or
    • Dijon, Cote-d Or, France, 21000
      • CHU Dijon Bourgogne ( Site 0320)
  • Gironde
    • Bordeaux, Gironde, France, 33075
      • CHU de Bordeaux- Hopital Saint Andre ( Site 0304)
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31059
      • Institut Claudius Regaud IUCT Oncopole ( Site 0306)
  • Hauts-de-Seine
    • Boulogne-Billancourt, Hauts-de-Seine, France, 92100
      • Hopital Ambroise Pare Boulogne ( Site 0316)
  • Herault
    • Montpellier, Herault, France, 34295
      • CHU Montpellier. ( Site 0312)
  • Ille-et-Vilaine
    • Rennes, Ille-et-Vilaine, France, 35042
      • Centre Eugene Marquis ( Site 0305)
  • Maine-et-Loire
    • Angers, Maine-et-Loire, France, 49933
      • CHU Angers ( Site 0321)
  • Marne
    • Reims, Marne, France, 51100
      • CHU de Reims ( Site 0307)
  • Nord
    • Lille, Nord, France, 59037
      • CHRU Lille - Hopital Claude Huriez ( Site 0301)
  • Rhone
    • Pierre Benite, Rhone, France, 69495
      • C.H.U. Lyon Sud ( Site 0303)
  • Somme
    • Amiens, Somme, France, 80054
      • CHU Amiens Picardie Hopital Nord ( Site 0317)
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94805
      • Institut Gustave Roussy ( Site 0300)
• Germany
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg Eppendorf (UKE) ( Site 0352)
  • Baden-Wurttemberg
    • Mannheim, Baden-Wurttemberg, Germany, 68135
      • Universitaetsklinikum in Mannheim ( Site 0351)
    • Tuebingen, Baden-Wurttemberg, Germany, 72076
      • Universitaetsklinikum Tuebingen ( Site 0353)
  • Bayern
    • Muenchen, Bayern, Germany, 80337
      • Klinikum der Ludwig-Maximilians-Universitaet Muenchen ( Site 0357)
    • Nuernberg, Bayern, Germany, 90419
      • Klinikum Nuernberg Nord ( Site 0355)
    • Wuerzburg, Bayern, Germany, 97080
      • Klinikum der Universitaet in Wuerzburg ( Site 0356)
  • Niedersachsen
    • Buxtehude, Niedersachsen, Germany, 21614
      • Elbe Klinikum Buxtehude ( Site 0354)
    • Hannover, Niedersachsen, Germany, 30625
      • Medizinische Hochschule Hannover ( Site 0358)
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45147
      • Klinik und Poliklinik fuer Dermatologie Venerologie und Allergologie ( Site 0361)
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Universitaetsklinikum Schleswig-Holstein Campus Kiel ( Site 0359)
  • Thuringen
    • Gera, Thuringen, Germany, 07548
      • SRH Wald-Klinikum Gera GmbH ( Site 0360)
• Israel
  • Afula, Israel, 1834111
    • HaEmek Medical Center ( Site 0655)
  • Haifa, Israel, 3109601
    • Rambam Medical Center ( Site 0654)
  • Jerusalem, Israel, 9112001
    • Hadassah Ein Kerem Medical Center ( Site 0651)
  • Ramat Gan, Israel, 5262000
    • Chaim Sheba Medical Center. ( Site 0652)
  • Zerifin, Israel, 70300
    • Shamir Medical Center-Assaf Harofeh ( Site 0657)
  • Southern
    • Beer Sheva, Southern, Israel, 8457108
      • Soroka Medical Center ( Site 0653)
  • Tell Abib
    • Tel Aviv, Tell Abib, Israel, 6423906
      • Sourasky Medical Center ( Site 0656)
• Italy
  • Bari, Italy, 70124
    • IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 0406)
  • Bergamo, Italy, 24127
    • ASST Papa Giovanni XXIII ( Site 0402)
  • Genova, Italy, 16132
    • IRCCS A.O.U. San Martino - IST ( Site 0404)
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0408)
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori Fondazione Pascale ( Site 0400)
  • Padova, Italy, 35128
    • IRCCS Istituto Oncologico Veneto ( Site 0407)
  • Roma, Italy, 00167
    • IDI - Istituto Dermopatico dell'Immacolata ( Site 0405)
  • Siena, Italy, 53100
    • Azienda Ospedaliero Universitaria Senese ( Site 0401)
  • Forli-Cesena
    • Meldola, Forli-Cesena, Italy, 47014
      • Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 0403)
• Japan
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital ( Site 0910)
• Poland
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-796
      • Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0769)
  • Malopolskie
    • Krakow, Malopolskie, Poland, 30-510
      • Pratia MCM Krakow ( Site 0773)
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-781
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0751)
    • Warszawa, Mazowieckie, Poland, 04-730
      • Instytut Pomnik Centrum Zdrowia Dziecka ( Site 0759)
  • Podkarpackie
    • Rzeszow, Podkarpackie, Poland, 35-055
      • Kliniczny Szpital Wojewodzki Nr 1 ( Site 0758)
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-402
      • Uniwersyteckie Centrum Kliniczne ( Site 0770)
  • Slaskie
    • Bielsko-Biala, Slaskie, Poland, 43-300
      • Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 0754)
    • Katowice, Slaskie, Poland, 40-514
      • Uniwersyteckie Centrum Kliniczne Slaskiego Uniwersytetu Medycznego ( Site 0757)
    • Rybnik, Slaskie, Poland, 44-200
      • LIFTMED ( Site 0765)
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 60-780
      • Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 0753)
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6045
      • Cancer Care Langenhoven Drive Oncology Centre ( Site 0812)
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2196
      • Sandton Oncology Medical Group PTY LTD ( Site 0801)
    • Parktown, Gauteng, South Africa, 2196
      • Charlotte Maxeke Johannesburg Academic Hospital ( Site 0811)
    • Pretoria, Gauteng, South Africa, 0081
      • Wilgers Oncology Centre ( Site 0806)
    • Pretoria, Gauteng, South Africa, 0181
      • MPOC ( Site 0803)
  • Limpopo
    • Cape Town, Limpopo, South Africa, 7700
      • Cancercare ( Site 0810)
  • Western Cape
    • Kraaifontein, Western Cape, South Africa, 7570
      • Cape Town Oncology Trials Pty Ltd ( Site 0807)
• Spain
  • Barcelona, Spain, 08035
    • Hospital General Universitari Vall d Hebron ( Site 0456)
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona ( Site 0452)
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Maranon ( Site 0454)
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena ( Site 0455)
  • Gipuzkoa
    • San Sebastian, Gipuzkoa, Spain, 20014
      • Onkologikoa - Instituto Oncologico de San Sebastian ( Site 0457)
  • Valenciana, Comunitat
    • Valencia, Valenciana, Comunitat, Spain, 46014
      • Hospital General Universitario de Valencia ( Site 0451)
• Switzerland
  • Basel-Stadt
    • Basel, Basel-Stadt, Switzerland, 4031
      • Universitaetsspital Basel ( Site 0554)
  • Berne
    • Bern, Berne, Switzerland, 3010
      • Universitaetsspital Bern ( Site 0552)
  • Geneve
    • Geneva, Geneve, Switzerland, 1211
      • Hopitaux Universitaires de Geneve HUG ( Site 0556)
  • Grisons
    • Chur, Grisons, Switzerland, 7000
      • Kantonsspital Graubuenden ( Site 0555)
  • Sankt Gallen
    • St. Gallen, Sankt Gallen, Switzerland, 9007
      • Kantonsspital St. Gallen ( Site 0559)
  • Ticino
    • Bellinzona, Ticino, Switzerland, 6500
      • Oncological Institute of Southern Switzerland ( Site 0557)
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • Centre Hospitalier Universitaire Vaudois ( Site 0553)
  • Wallis
    • Sion, Wallis, Switzerland, 1951
      • Hopital du Valais ( Site 0558)
  • Zurich
    • Zuerich, Zurich, Switzerland, 8091
      • Universitaetsspital Zuerich ( Site 0551)
• United Kingdom
  • Manchester, United Kingdom, M20 4GJ
    • Christie NHS Foundation Trust ( Site 0604)
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Addenbrooke's Hospital in Cambridge ( Site 0600)
  • London, City Of
    • London, London, City Of, United Kingdom, SE1 9RT
      • Guy s & St Thomas NHS Foundation Trust ( Site 0601)
    • London, London, City Of, United Kingdom, SW3 6JJ
      • Royal Marsden Hospital - Fulham Road London ( Site 0613)
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • The Royal Marsden NHS Foundation Trust. ( Site 0612)
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center ( Site 0121)
  • California
    • La Jolla, California, United States, 92037
      • UCSD Moores Cancer Center ( Site 0133)
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute ( Site 0029)
    • Los Angeles, California, United States, 90095
      • UCLA Hematology & Oncology ( Site 0130)
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Institute ( Site 0026)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center ( Site 0027)
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University ( Site 0035)
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida ( Site 0024)
    • Tampa, Florida, United States, 33612
      • Moffitt McKinley Outpatient Center ( Site 0131)
  • Georgia
    • Atlanta, Georgia, United States, 30322-1013
      • Winship Cancer Institute of Emory University ( Site 0046)
    • Atlanta, Georgia, United States, 30341
      • Northside Hospital ( Site 0115)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Medical Group ( Site 0135)
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center ( Site 0007)
    • Park Ridge, Illinois, United States, 60068
      • Advocate Medical Group-Park Ridge ( Site 0025)
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital and Clinics ( Site 0001)
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 0047)
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital ( Site 0126)
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center ( Site 0141)
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute ( Site 0124)
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute ( Site 0111)
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic [Rochester, MN] ( Site 0016)
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center ( Site 0143)
  • New York
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering ( Site 0006)
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center ( Site 0137)
    • New York, New York, United States, 10022
      • Memorial Sloan Kettering Cancer Center ( Site 0142)
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center ( Site 0038)
    • Rochester, New York, United States, 14642
      • University of Rochester ( Site 0019)
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Center for Research and Education at The Christ Hospital ( Site 0004)
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center ( Site 0042)
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University ( Site 0032)
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh UPMC ( Site 0144)
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Centers ( Site 0043)
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • West Cancer Center - East Campus ( Site 0022)
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center Knoxville ( Site 0116)
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas-MD Anderson Cancer Center ( Site 0134)
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute ( Site 0014)
    • Richmond, Virginia, United States, 23298
      • VCU Massey Cancer Center ( Site 0008)
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance ( Site 0044)
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics ( Site 0030)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion:

• Has surgically resected and histologically/pathologically confirmed new diagnosis of Stage IIB or IIC cutaneous melanoma per American Joint Committee on Cancer (AJCC) 8th edition guidelines
• Has not been previously treated for melanoma beyond complete surgical resection
• Has ≤12 weeks between final surgical resection and randomization
• Has no evidence of metastatic disease on imaging as determined by investigator
• Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale or Lansky Play-Performance Scale (LPS) score ≥50 for participants ≤16 years old, or a Karnofsky Performance Scale (KPS) score ≥50 for participants >16 and <18 years old
• Has recovered adequately from toxicity and/or complications from surgery prior to study start
• Female participants must not be pregnant or breastfeeding, and must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment if they are women of childbearing potential (WOCBP)

Exclusion:

• Has a known additional malignancy that is progressing or has required active antineoplastic therapy (including hormonal) within the past 5 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
• WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1), anti-Programmed Cell Death Receptor Ligand 1 (PD-L1) or anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
• Has received prior systemic anti-cancer therapy for melanoma including investigational agents
• Has received a live vaccine within 30 days prior to the first dose of study treatment
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
• Has severe hypersensitivity (≥Grade 3) to any excipients of pembrolizumab
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of hepatitis B (defined as hepatitis B surface antigen reactive) or known active hepatitis C virus (defined as hepatitis C virus ribonucleic acid [RNA] [qualitative] is detected) infection
• Has a history of active tuberculosis (Bacillus tuberculosis)
• 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 allogeneic tissue/solid organ transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: Pembrolizumab; Administered as an intravenous (IV) infusion every 3 weeks (Q3W); Other Names: MK-3475; KEYTRUDA®
Placebo Comparator: 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.	Biological: Pembrolizumab; Administered as an intravenous (IV) infusion every 3 weeks (Q3W); Other Names: MK-3475; KEYTRUDA®; Other: Placebo; Administered as an IV infusion every 3 weeks (Q3W)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free Survival (RFS)	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.	Up to ~32.7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distant Metastasis-free Survival (DMFS)	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.	Up to ~9 years
Overall Survival (OS)	OS will be defined as the time from randomization to death due to any cause. OS will be reported for randomized participants.	Up to ~15 years
Number of Participants Who Experienced at Least One Adverse Event (AE)	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.	Up to ~19.3 months
Number of Participants Who Discontinued Study Treatment Due to an AE	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.	Up to ~19.3 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Long GV, Luke JJ, Khattak MA, de la Cruz Merino L, Del Vecchio M, Rutkowski P, Spagnolo F, Mackiewicz J, Chiarion-Sileni V, Kirkwood JM, Robert C, Grob JJ, de Galitiis F, Schadendorf D, Carlino MS, Mohr P, Dummer R, Gershenwald JE, Yoon CH, Wu XL, Fukunaga-Kalabis M, Krepler C, Eggermont AMM, Ascierto PA; KEYNOTE-716 Investigators. Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma (KEYNOTE-716): distant metastasis-free survival results of a multicentre, double-blind, randomised, phase 3 trial. Lancet Oncol. 2022 Nov;23(11):1378-1388. doi: 10.1016/S1470-2045(22)00559-9. Epub 2022 Oct 18.
• Luke JJ, Rutkowski P, Queirolo P, Del Vecchio M, Mackiewicz J, Chiarion-Sileni V, de la Cruz Merino L, Khattak MA, Schadendorf D, Long GV, Ascierto PA, Mandala M, De Galitiis F, Haydon A, Dummer R, Grob JJ, Robert C, Carlino MS, Mohr P, Poklepovic A, Sondak VK, Scolyer RA, Kirkwood JM, Chen K, Diede SJ, Ahsan S, Ibrahim N, Eggermont AMM; KEYNOTE-716 Investigators. Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE-716): a randomised, double-blind, phase 3 trial. Lancet. 2022 Apr 30;399(10336):1718-1729. doi: 10.1016/S0140-6736(22)00562-1. Epub 2022 Apr 1.
• Luke JJ, Ascierto PA, Carlino MS, Gershenwald JE, Grob JJ, Hauschild A, Kirkwood JM, Long GV, Mohr P, Robert C, Ross M, Scolyer RA, Yoon CH, Poklepovic A, Rutkowski P, Anderson JR, Ahsan S, Ibrahim N, M Eggermont AM. KEYNOTE-716: Phase III study of adjuvant pembrolizumab versus placebo in resected high-risk stage II melanoma. Future Oncol. 2020 Jan;16(3):4429-4438. doi: 10.2217/fon-2019-0666. Epub 2019 Dec 24.

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2018
• Primary Completion (Actual): June 21, 2021
• Study Completion (Estimated): October 12, 2033

Study Registration Dates

• First Submitted: June 1, 2018
• First Submitted That Met QC Criteria: June 1, 2018
• First Posted (Actual): June 12, 2018

Study Record Updates

• Last Update Posted (Actual): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2); Programmed Cell Death 1 Ligand 1(PDL1, PD-L1)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 3475-716; 205203 (Registry Identifier: JAPIC-CTI); MK-3475-716 (Other Identifier: Merck); KEYNOTE-716 (Other Identifier: Merck); 2018-000669-35 (EudraCT Number); 2022-501966-23 (Registry Identifier: EU CT Number); U1111-1282-6109 (Other Identifier: Universal Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No