Safety and Efficacy of Pembrolizumab Compared to Placebo in Resected High-risk Stage II Melanoma (MK-3475-716/KEYNOTE-716)
Melanoma
About this trial
This is an interventional treatment trial for Melanoma focused on measuring Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1(PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Eligibility Criteria
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
Sites / Locations
- University of Arizona Cancer Center ( Site 0121)
- UCSD Moores Cancer Center ( Site 0133)
- The Angeles Clinic and Research Institute ( Site 0029)
- UCLA Hematology & Oncology ( Site 0130)
- John Wayne Cancer Institute ( Site 0026)
- University of Colorado Cancer Center ( Site 0027)
- Yale University ( Site 0035)
- Mayo Clinic Florida ( Site 0024)
- Moffitt McKinley Outpatient Center ( Site 0131)
- Winship Cancer Institute of Emory University ( Site 0046)
- Northside Hospital ( Site 0115)
- Northwestern Medical Group ( Site 0135)
- The University of Chicago Medical Center ( Site 0007)
- Advocate Medical Group-Park Ridge ( Site 0025)
- University of Iowa Hospital and Clinics ( Site 0001)
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 0047)
- Massachusetts General Hospital ( Site 0126)
- Beth Israel Deaconess Medical Center ( Site 0141)
- Dana Farber Cancer Institute ( Site 0124)
- Karmanos Cancer Institute ( Site 0111)
- Mayo Clinic [Rochester, MN] ( Site 0016)
- Siteman Cancer Center ( Site 0143)
- Memorial Sloan Kettering ( Site 0006)
- Laura and Isaac Perlmutter Cancer Center ( Site 0137)
- Memorial Sloan Kettering Cancer Center ( Site 0142)
- Mount Sinai Medical Center ( Site 0038)
- University of Rochester ( Site 0019)
- The Lindner Center for Research and Education at The Christ Hospital ( Site 0004)
- Stephenson Cancer Center ( Site 0042)
- Oregon Health & Science University ( Site 0032)
- Children's Hospital of Pittsburgh UPMC ( Site 0144)
- UPMC Hillman Cancer Centers ( Site 0043)
- West Cancer Center - East Campus ( Site 0022)
- University of Tennessee Medical Center Knoxville ( Site 0116)
- University of Texas-MD Anderson Cancer Center ( Site 0134)
- Inova Schar Cancer Institute ( Site 0014)
- VCU Massey Cancer Center ( Site 0008)
- Seattle Cancer Care Alliance ( Site 0044)
- University of Wisconsin Hospital and Clinics ( Site 0030)
- Melanoma Institute Australia ( Site 0856)
- Westmead Hospital ( Site 0853)
- Cairns Base Hospital ( Site 0859)
- Tasman Oncology Research Pty Ltd ( Site 0858)
- Princess Alexandra Hospital ( Site 0857)
- Royal Adelaide Hospital ( Site 0861)
- Ashford Cancer Centre Research ( Site 0860)
- The Alfred Hospital ( Site 0852)
- Fiona Stanley Hospital ( Site 0851)
- GZA Sint Augustinus ( Site 0259)
- Cliniques Universitaires Saint-Luc ( Site 0251)
- Institut Jules Bordet ( Site 0254)
- Jessa Ziekenhuis Campus Virga Jesse ( Site 0256)
- UZ Gent ( Site 0255)
- UZ Leuven ( Site 0252)
- Hospital Erasto Gaertner ( Site 0159)
- Hospital de Caridade de Ijui ( Site 0156)
- Hospital Sao Vicente de Paulo ( Site 0158)
- Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0154)
- Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 0155)
- Hospital de Clinicas de Rio Preto ( Site 0162)
- Instituto Nacional do Cancer II ( Site 0160)
- Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0151)
- Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 0161)
- A.C. Camargo Cancer Center ( Site 0164)
- Cross Cancer Institute ( Site 0057)
- CancerCare Manitoba ( Site 0053)
- Moncton Hospital - Horizon Health Network ( Site 0055)
- The Ottawa Hospital ( Site 0058)
- Sunnybrook Research Institute ( Site 0060)
- Princess Margaret Cancer Centre ( Site 0059)
- Hopital Maisonneuve Rosemont ( Site 0056)
- Jewish General Hospital ( Site 0054)
- McGill University Health Centre ( Site 0062)
- CHU de Quebec - Hotel-Dieu de Quebec ( Site 0061)
- Instituto Clinico Oncologico del Sur ( Site 0203)
- Fundacion Arturo Lopez Perez FALP ( Site 0200)
- Pontificia Universidad Catolica de Chile ( Site 0201)
- Sociedad Medica Aren y Bachero Limitada ( Site 0207)
- Oncocentro ( Site 0204)
- Centro Oncologico Antofagasta ( Site 0206)
- Hopital La Timone ( Site 0302)
- CHU Dijon Bourgogne ( Site 0320)
- CHU de Bordeaux- Hopital Saint Andre ( Site 0304)
- Institut Claudius Regaud IUCT Oncopole ( Site 0306)
- Hopital Ambroise Pare Boulogne ( Site 0316)
- CHU Montpellier. ( Site 0312)
- Centre Eugene Marquis ( Site 0305)
- CHU Angers ( Site 0321)
- CHU de Reims ( Site 0307)
- CHRU Lille - Hopital Claude Huriez ( Site 0301)
- C.H.U. Lyon Sud ( Site 0303)
- CHU Amiens Picardie Hopital Nord ( Site 0317)
- Institut Gustave Roussy ( Site 0300)
- Hopital Saint Louis ( Site 0322)
- Universitaetsklinikum in Mannheim ( Site 0351)
- Universitaetsklinikum Tuebingen ( Site 0353)
- Klinikum der Ludwig-Maximilians-Universitaet Muenchen ( Site 0357)
- Klinikum Nuernberg Nord ( Site 0355)
- Klinikum der Universitaet in Wuerzburg ( Site 0356)
- Elbe Klinikum Buxtehude ( Site 0354)
- Medizinische Hochschule Hannover ( Site 0358)
- Klinik und Poliklinik fuer Dermatologie Venerologie und Allergologie ( Site 0361)
- Universitaetsklinikum Schleswig-Holstein Campus Kiel ( Site 0359)
- SRH Wald-Klinikum Gera GmbH ( Site 0360)
- Universitaetsklinikum Hamburg Eppendorf (UKE) ( Site 0352)
- Soroka Medical Center ( Site 0653)
- Sourasky Medical Center ( Site 0656)
- HaEmek Medical Center ( Site 0655)
- Rambam Medical Center ( Site 0654)
- Hadassah Ein Kerem Medical Center ( Site 0651)
- Chaim Sheba Medical Center. ( Site 0652)
- Shamir Medical Center-Assaf Harofeh ( Site 0657)
- Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 0403)
- IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 0406)
- ASST Papa Giovanni XXIII ( Site 0402)
- IRCCS A.O.U. San Martino - IST ( Site 0404)
- Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0408)
- Istituto Nazionale Tumori Fondazione Pascale ( Site 0400)
- IRCCS Istituto Oncologico Veneto ( Site 0407)
- IDI - Istituto Dermopatico dell'Immacolata ( Site 0405)
- Azienda Ospedaliero Universitaria Senese ( Site 0401)
- National Cancer Center Hospital ( Site 0910)
- Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0769)
- Pratia MCM Krakow ( Site 0773)
- Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0751)
- Instytut Pomnik Centrum Zdrowia Dziecka ( Site 0759)
- Kliniczny Szpital Wojewodzki Nr 1 ( Site 0758)
- Uniwersyteckie Centrum Kliniczne ( Site 0770)
- Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 0754)
- Uniwersyteckie Centrum Kliniczne Slaskiego Uniwersytetu Medycznego ( Site 0757)
- LIFTMED ( Site 0765)
- Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 0753)
- Cancer Care Langenhoven Drive Oncology Centre ( Site 0812)
- Sandton Oncology Medical Group PTY LTD ( Site 0801)
- Charlotte Maxeke Johannesburg Academic Hospital ( Site 0811)
- Wilgers Oncology Centre ( Site 0806)
- MPOC ( Site 0803)
- Cancercare ( Site 0810)
- Cape Town Oncology Trials Pty Ltd ( Site 0807)
- Onkologikoa - Instituto Oncologico de San Sebastian ( Site 0457)
- Hospital General Universitario de Valencia ( Site 0451)
- Hospital General Universitari Vall d Hebron ( Site 0456)
- Hospital Clinic de Barcelona ( Site 0452)
- Hospital General Universitario Gregorio Maranon ( Site 0454)
- Hospital Universitario Virgen Macarena ( Site 0455)
- Universitaetsspital Basel ( Site 0554)
- Universitaetsspital Bern ( Site 0552)
- Hopitaux Universitaires de Geneve HUG ( Site 0556)
- Kantonsspital Graubuenden ( Site 0555)
- Kantonsspital St. Gallen ( Site 0559)
- Oncological Institute of Southern Switzerland ( Site 0557)
- Centre Hospitalier Universitaire Vaudois ( Site 0553)
- Hopital du Valais ( Site 0558)
- Universitaetsspital Zuerich ( Site 0551)
- Addenbrooke's Hospital in Cambridge ( Site 0600)
- Guy s & St Thomas NHS Foundation Trust ( Site 0601)
- Royal Marsden Hospital - Fulham Road London ( Site 0613)
- The Royal Marsden NHS Foundation Trust. ( Site 0612)
- Christie NHS Foundation Trust ( Site 0604)
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Pembrolizumab
Placebo
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.
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.