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

NCT ID: NCT03553836

Last Updated: 2024-11-29

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

976 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-12

Study Completion Date

2033-10-12

Brief Summary

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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

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Conditions

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Melanoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
Participants and Investigators will be blinded in Part 1 and unblinded in Part 2, if done.

Study Groups

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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.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

Administered as an intravenous (IV) infusion every 3 weeks (Q3W)

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.

Group Type PLACEBO_COMPARATOR

Pembrolizumab

Intervention Type BIOLOGICAL

Administered as an intravenous (IV) infusion every 3 weeks (Q3W)

Placebo

Intervention Type OTHER

Administered as an IV infusion every 3 weeks (Q3W)

Interventions

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Pembrolizumab

Administered as an intravenous (IV) infusion every 3 weeks (Q3W)

Intervention Type BIOLOGICAL

Placebo

Administered as an IV infusion every 3 weeks (Q3W)

Intervention Type OTHER

Other Intervention Names

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KEYTRUDA® MK-3475

Eligibility Criteria

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Inclusion Criteria

* 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
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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University of Arizona Cancer Center ( Site 0121)

Tucson, Arizona, United States

Site Status

UCSD Moores Cancer Center ( Site 0133)

La Jolla, California, United States

Site Status

The Angeles Clinic and Research Institute ( Site 0029)

Los Angeles, California, United States

Site Status

UCLA Hematology & Oncology ( Site 0130)

Los Angeles, California, United States

Site Status

John Wayne Cancer Institute ( Site 0026)

Santa Monica, California, United States

Site Status

University of Colorado Cancer Center ( Site 0027)

Aurora, Colorado, United States

Site Status

Yale University ( Site 0035)

New Haven, Connecticut, United States

Site Status

Mayo Clinic Florida ( Site 0024)

Jacksonville, Florida, United States

Site Status

Moffitt McKinley Outpatient Center ( Site 0131)

Tampa, Florida, United States

Site Status

Winship Cancer Institute of Emory University ( Site 0046)

Atlanta, Georgia, United States

Site Status

Northside Hospital ( Site 0115)

Atlanta, Georgia, United States

Site Status

Northwestern Medical Group ( Site 0135)

Chicago, Illinois, United States

Site Status

The University of Chicago Medical Center ( Site 0007)

Chicago, Illinois, United States

Site Status

Advocate Medical Group-Park Ridge ( Site 0025)

Park Ridge, Illinois, United States

Site Status

University of Iowa Hospital and Clinics ( Site 0001)

Iowa City, Iowa, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 0047)

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital ( Site 0126)

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center ( Site 0141)

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute ( Site 0124)

Boston, Massachusetts, United States

Site Status

Karmanos Cancer Institute ( Site 0111)

Detroit, Michigan, United States

Site Status

Mayo Clinic [Rochester, MN] ( Site 0016)

Rochester, Minnesota, United States

Site Status

Siteman Cancer Center ( Site 0143)

St Louis, Missouri, United States

Site Status

Memorial Sloan Kettering ( Site 0006)

Harrison, New York, United States

Site Status

Laura and Isaac Perlmutter Cancer Center ( Site 0137)

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center ( Site 0142)

New York, New York, United States

Site Status

Mount Sinai Medical Center ( Site 0038)

New York, New York, United States

Site Status

University of Rochester ( Site 0019)

Rochester, New York, United States

Site Status

The Lindner Center for Research and Education at The Christ Hospital ( Site 0004)

Cincinnati, Ohio, United States

Site Status

Stephenson Cancer Center ( Site 0042)

Oklahoma City, Oklahoma, United States

Site Status

Oregon Health & Science University ( Site 0032)

Portland, Oregon, United States

Site Status

Children's Hospital of Pittsburgh UPMC ( Site 0144)

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Hillman Cancer Centers ( Site 0043)

Pittsburgh, Pennsylvania, United States

Site Status

West Cancer Center - East Campus ( Site 0022)

Germantown, Tennessee, United States

Site Status

University of Tennessee Medical Center Knoxville ( Site 0116)

Knoxville, Tennessee, United States

Site Status

University of Texas-MD Anderson Cancer Center ( Site 0134)

Houston, Texas, United States

Site Status

Inova Schar Cancer Institute ( Site 0014)

Fairfax, Virginia, United States

Site Status

VCU Massey Cancer Center ( Site 0008)

Richmond, Virginia, United States

Site Status

Seattle Cancer Care Alliance ( Site 0044)

Seattle, Washington, United States

Site Status

University of Wisconsin Hospital and Clinics ( Site 0030)

Madison, Wisconsin, United States

Site Status

Melanoma Institute Australia ( Site 0856)

North Sydney, New South Wales, Australia

Site Status

Westmead Hospital ( Site 0853)

Westmead, New South Wales, Australia

Site Status

Cairns Base Hospital ( Site 0859)

Cairns, Queensland, Australia

Site Status

Tasman Oncology Research Pty Ltd ( Site 0858)

Southport, Queensland, Australia

Site Status

Princess Alexandra Hospital ( Site 0857)

Woolloongabba, Queensland, Australia

Site Status

Royal Adelaide Hospital ( Site 0861)

Adelaide, South Australia, Australia

Site Status

Ashford Cancer Centre Research ( Site 0860)

Kurralta Park, South Australia, Australia

Site Status

The Alfred Hospital ( Site 0852)

Melbourne, Victoria, Australia

Site Status

Fiona Stanley Hospital ( Site 0851)

Murdoch, Western Australia, Australia

Site Status

GZA Sint Augustinus ( Site 0259)

Wilrijk - Antwerpen, Antwerpen, Belgium

Site Status

Institut Jules Bordet ( Site 0254)

Brussels, Bruxelles-Capitale, Region de, Belgium

Site Status

Cliniques Universitaires Saint-Luc ( Site 0251)

Brussels, Bruxelles-Capitale, Region de, Belgium

Site Status

Jessa Ziekenhuis Campus Virga Jesse ( Site 0256)

Hasselt, Limburg, Belgium

Site Status

UZ Gent ( Site 0255)

Ghent, Oost-Vlaanderen, Belgium

Site Status

UZ Leuven ( Site 0252)

Leuven, Vlaams-Brabant, Belgium

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Hospital Erasto Gaertner ( Site 0159)

Curitiba, Paraná, Brazil

Site Status

Hospital de Caridade de Ijui ( Site 0156)

Ijuí, Rio Grande do Sul, Brazil

Site Status

Hospital Sao Vicente de Paulo ( Site 0158)

Passo Fundo, Rio Grande do Sul, Brazil

Site Status

Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0154)

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 0155)

Barretos, São Paulo, Brazil

Site Status

Hospital de Clinicas de Rio Preto ( Site 0162)

Sao Jose Do Rio Preto - SP, São Paulo, Brazil

Site Status

Instituto Nacional do Cancer II ( Site 0160)

Rio de Janeiro, , Brazil

Site Status

Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0151)

São Paulo, , Brazil

Site Status

Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 0161)

São Paulo, , Brazil

Site Status

A.C. Camargo Cancer Center ( Site 0164)

São Paulo, , Brazil

Site Status

Cross Cancer Institute ( Site 0057)

Edmonton, Alberta, Canada

Site Status

CancerCare Manitoba ( Site 0053)

Winnipeg, Manitoba, Canada

Site Status

Moncton Hospital - Horizon Health Network ( Site 0055)

Moncton, New Brunswick, Canada

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The Ottawa Hospital ( Site 0058)

Ottawa, Ontario, Canada

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Sunnybrook Research Institute ( Site 0060)

Toronto, Ontario, Canada

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Princess Margaret Cancer Centre ( Site 0059)

Toronto, Ontario, Canada

Site Status

Hopital Maisonneuve Rosemont ( Site 0056)

Montreal, Quebec, Canada

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Jewish General Hospital ( Site 0054)

Montreal, Quebec, Canada

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McGill University Health Centre ( Site 0062)

Montreal, Quebec, Canada

Site Status

CHU de Quebec - Hotel-Dieu de Quebec ( Site 0061)

Québec, Quebec, Canada

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Fundacion Arturo Lopez Perez FALP ( Site 0200)

Santiago, Region M. de Santiago, Chile

Site Status

Pontificia Universidad Catolica de Chile ( Site 0201)

Santiago, Region M. de Santiago, Chile

Site Status

Sociedad Medica Aren y Bachero Limitada ( Site 0207)

Santiago, Region M. de Santiago, Chile

Site Status

Instituto Clinico Oncologico del Sur ( Site 0203)

Temuco, Región de la Araucanía, Chile

Site Status

Oncocentro ( Site 0204)

Viña del Mar, Región de Valparaíso, Chile

Site Status

Centro Oncologico Antofagasta ( Site 0206)

Antofagasta, , Chile

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Hopital La Timone ( Site 0302)

Marseille, Bouches-du-Rhone, France

Site Status

CHU Dijon Bourgogne ( Site 0320)

Dijon, Cote-d Or, France

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CHU de Bordeaux- Hopital Saint Andre ( Site 0304)

Bordeaux, Gironde, France

Site Status

Institut Claudius Regaud IUCT Oncopole ( Site 0306)

Toulouse, Haute-Garonne, France

Site Status

Hopital Ambroise Pare Boulogne ( Site 0316)

Boulogne-Billancourt, Hauts-de-Seine, France

Site Status

CHU Montpellier. ( Site 0312)

Montpellier, Herault, France

Site Status

Centre Eugene Marquis ( Site 0305)

Rennes, Ille-et-Vilaine, France

Site Status

CHU Angers ( Site 0321)

Angers, Maine-et-Loire, France

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CHU de Reims ( Site 0307)

Reims, Marne, France

Site Status

CHRU Lille - Hopital Claude Huriez ( Site 0301)

Lille, Nord, France

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C.H.U. Lyon Sud ( Site 0303)

Pierre-Bénite, Rhone, France

Site Status

CHU Amiens Picardie Hopital Nord ( Site 0317)

Amiens, Somme, France

Site Status

Institut Gustave Roussy ( Site 0300)

Villejuif, Val-de-Marne, France

Site Status

Hopital Saint Louis ( Site 0322)

Paris, , France

Site Status

Universitaetsklinikum in Mannheim ( Site 0351)

Mannheim, Baden-Wurttemberg, Germany

Site Status

Universitaetsklinikum Tuebingen ( Site 0353)

Tübingen, Baden-Wurttemberg, Germany

Site Status

Klinikum der Ludwig-Maximilians-Universitaet Muenchen ( Site 0357)

Munich, Bavaria, Germany

Site Status

Klinikum Nuernberg Nord ( Site 0355)

Nuremberg, Bavaria, Germany

Site Status

Klinikum der Universitaet in Wuerzburg ( Site 0356)

Würzburg, Bavaria, Germany

Site Status

Elbe Klinikum Buxtehude ( Site 0354)

Buxtehude, Lower Saxony, Germany

Site Status

Medizinische Hochschule Hannover ( Site 0358)

Hanover, Lower Saxony, Germany

Site Status

Klinik und Poliklinik fuer Dermatologie Venerologie und Allergologie ( Site 0361)

Essen, North Rhine-Westphalia, Germany

Site Status

Universitaetsklinikum Schleswig-Holstein Campus Kiel ( Site 0359)

Kiel, Schleswig-Holstein, Germany

Site Status

SRH Wald-Klinikum Gera GmbH ( Site 0360)

Gera, Thuringia, Germany

Site Status

Universitaetsklinikum Hamburg Eppendorf (UKE) ( Site 0352)

Hamburg, , Germany

Site Status

Soroka Medical Center ( Site 0653)

Beersheba, Southern District, Israel

Site Status

Sourasky Medical Center ( Site 0656)

Tel Aviv, Tell Abib, Israel

Site Status

HaEmek Medical Center ( Site 0655)

Afula, , Israel

Site Status

Rambam Medical Center ( Site 0654)

Haifa, , Israel

Site Status

Hadassah Ein Kerem Medical Center ( Site 0651)

Jerusalem, , Israel

Site Status

Chaim Sheba Medical Center. ( Site 0652)

Ramat Gan, , Israel

Site Status

Shamir Medical Center-Assaf Harofeh ( Site 0657)

Ẕerifin, , Israel

Site Status

Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 0403)

Meldola, Forli-Cesena, Italy

Site Status

IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 0406)

Bari, , Italy

Site Status

ASST Papa Giovanni XXIII ( Site 0402)

Bergamo, , Italy

Site Status

IRCCS A.O.U. San Martino - IST ( Site 0404)

Genova, , Italy

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0408)

Milan, , Italy

Site Status

Istituto Nazionale Tumori Fondazione Pascale ( Site 0400)

Napoli, , Italy

Site Status

IRCCS Istituto Oncologico Veneto ( Site 0407)

Padua, , Italy

Site Status

IDI - Istituto Dermopatico dell'Immacolata ( Site 0405)

Roma, , Italy

Site Status

Azienda Ospedaliero Universitaria Senese ( Site 0401)

Siena, , Italy

Site Status

National Cancer Center Hospital ( Site 0910)

Tokyo, , Japan

Site Status

Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 0753)

Poznan, Greater Poland Voivodeship, Poland

Site Status

Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0769)

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Site Status

Pratia MCM Krakow ( Site 0773)

Krakow, Lesser Poland Voivodeship, Poland

Site Status

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0751)

Warsaw, Masovian Voivodeship, Poland

Site Status

Instytut Pomnik Centrum Zdrowia Dziecka ( Site 0759)

Warsaw, Masovian Voivodeship, Poland

Site Status

Kliniczny Szpital Wojewodzki Nr 1 ( Site 0758)

Rzeszów, Podkarpackie Voivodeship, Poland

Site Status

Uniwersyteckie Centrum Kliniczne ( Site 0770)

Gdansk, Pomeranian Voivodeship, Poland

Site Status

Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 0754)

Bielsko-Biala, Silesian Voivodeship, Poland

Site Status

Uniwersyteckie Centrum Kliniczne Slaskiego Uniwersytetu Medycznego ( Site 0757)

Katowice, Silesian Voivodeship, Poland

Site Status

LIFTMED ( Site 0765)

Rybnik, Silesian Voivodeship, Poland

Site Status

Cancer Care Langenhoven Drive Oncology Centre ( Site 0812)

Port Elizabeth, Eastern Cape, South Africa

Site Status

Sandton Oncology Medical Group PTY LTD ( Site 0801)

Johannesburg, Gauteng, South Africa

Site Status

Charlotte Maxeke Johannesburg Academic Hospital ( Site 0811)

Parktown, Gauteng, South Africa

Site Status

Wilgers Oncology Centre ( Site 0806)

Pretoria, Gauteng, South Africa

Site Status

MPOC ( Site 0803)

Pretoria, Gauteng, South Africa

Site Status

Cancercare ( Site 0810)

Cape Town, Limpopo, South Africa

Site Status

Cape Town Oncology Trials Pty Ltd ( Site 0807)

Kraaifontein, Western Cape, South Africa

Site Status

Onkologikoa - Instituto Oncologico de San Sebastian ( Site 0457)

Donostia / San Sebastian, Gipuzkoa, Spain

Site Status

Hospital General Universitario de Valencia ( Site 0451)

Valencia, Valenciana, Comunitat, Spain

Site Status

Hospital General Universitari Vall d Hebron ( Site 0456)

Barcelona, , Spain

Site Status

Hospital Clinic de Barcelona ( Site 0452)

Barcelona, , Spain

Site Status

Hospital General Universitario Gregorio Maranon ( Site 0454)

Madrid, , Spain

Site Status

Hospital Universitario Virgen Macarena ( Site 0455)

Seville, , Spain

Site Status

Universitaetsspital Basel ( Site 0554)

Basel, Canton of Basel-City, Switzerland

Site Status

Universitaetsspital Bern ( Site 0552)

Bern, Canton of Bern, Switzerland

Site Status

Hopitaux Universitaires de Geneve HUG ( Site 0556)

Geneva, Canton of Geneva, Switzerland

Site Status

Kantonsspital St. Gallen ( Site 0559)

Sankt Gallen, Canton of St. Gallen, Switzerland

Site Status

Centre Hospitalier Universitaire Vaudois ( Site 0553)

Lausanne, Canton of Vaud, Switzerland

Site Status

Universitaetsspital Zuerich ( Site 0551)

Zurich, Canton of Zurich, Switzerland

Site Status

Oncological Institute of Southern Switzerland ( Site 0557)

Bellinzona, Canton Ticino, Switzerland

Site Status

Kantonsspital Graubuenden ( Site 0555)

Chur, Kanton Graubünden, Switzerland

Site Status

Hopital du Valais ( Site 0558)

Sion, Valais, Switzerland

Site Status

Addenbrooke's Hospital in Cambridge ( Site 0600)

Cambridge, Cambridgeshire, United Kingdom

Site Status

Guy s & St Thomas NHS Foundation Trust ( Site 0601)

London, London, City of, United Kingdom

Site Status

Royal Marsden Hospital - Fulham Road London ( Site 0613)

London, London, City of, United Kingdom

Site Status

The Royal Marsden NHS Foundation Trust. ( Site 0612)

Sutton, Surrey, United Kingdom

Site Status

Christie NHS Foundation Trust ( Site 0604)

Manchester, , United Kingdom

Site Status

Countries

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United States Australia Belgium Brazil Canada Chile France Germany Israel Italy Japan Poland South Africa Spain Switzerland United Kingdom

References

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Luke JJ, Ascierto PA, 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, Wu XL, Fukunaga-Kalabis M, Krepler C, Eggermont AMM, Long GV. Pembrolizumab Versus Placebo as Adjuvant Therapy in Resected Stage IIB or IIC Melanoma: Final Analysis of Distant Metastasis-Free Survival in the Phase III KEYNOTE-716 Study. J Clin Oncol. 2024 May 10;42(14):1619-1624. doi: 10.1200/JCO.23.02355. Epub 2024 Mar 7.

Reference Type RESULT
PMID: 38452313 (View on PubMed)

Luke JJ, Ascierto PA, Khattak MA, Rutkowski P, Del Vecchio M, Spagnolo F, Mackiewicz J, Merino LC, Chiarion-Sileni V, Kirkwood JM, Robert C, Schadendorf D, de Galitiis F, Carlino MS, Dummer R, Mohr P, Odeleye-Ajakaye A, Fukunaga-Kalabis M, Krepler C, Eggermont AMM, Long GV. Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Long-term follow-up, crossover, and rechallenge with pembrolizumab in the phase III KEYNOTE-716 study. Eur J Cancer. 2025 May 2;220:115381. doi: 10.1016/j.ejca.2025.115381. Epub 2025 Mar 23.

Reference Type DERIVED
PMID: 40198940 (View on PubMed)

Wurcel V, Rojas Rojas M, Urrego-Reyes J, Medrano Rivera D, Acevedo R, Jiang R, Jiang S, Zhang S, Caparros A, Krepler C, Fukunaga-Kalabis M, Younan ND, Alexander D, Hughes R, Weston G. Number needed to treat (NNT) with pembrolizumab as an adjuvant therapy in resected patients with high-risk stage II (IIB and IIC) melanoma and its application to cost of preventing an event (COPE) in Mexico. J Med Econ. 2025 Dec;28(1):346-353. doi: 10.1080/13696998.2025.2466365. Epub 2025 Mar 13.

Reference Type DERIVED
PMID: 40078077 (View on PubMed)

Schadendorf D, Luke JJ, Ascierto PA, Long GV, Rutkowski P, Khattak A, Del Vecchio M, de la Cruz-Merino L, Mackiewicz J, Sileni VC, Kirkwood JM, Robert C, Grob JJ, Dummer R, Carlino MS, Zhao Y, Kalabis M, Krepler C, Eggermont A, Scolyer RA. Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Outcomes in histopathologic subgroups from the randomized, double-blind, phase 3 KEYNOTE-716 trial. J Immunother Cancer. 2024 Mar 13;12(3):e007501. doi: 10.1136/jitc-2023-007501.

Reference Type DERIVED
PMID: 38485189 (View on PubMed)

Favre-Bulle A, Bencina G, Zhang S, Jiang R, Andritschke D, Bhadhuri A. Cost-effectiveness of pembrolizumab as an adjuvant treatment for patients with resected stage IIB or IIC melanoma in Switzerland. J Med Econ. 2023 Jan-Dec;26(1):283-292. doi: 10.1080/13696998.2023.2174748.

Reference Type DERIVED
PMID: 36748342 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36265502 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35367007 (View on PubMed)

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.

Reference Type DERIVED
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Provided Documents

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Document Type: Study Protocol

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Document Type: Statistical Analysis Plan

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Related Links

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Other Identifiers

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MK-3475-716

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-716

Identifier Type: OTHER

Identifier Source: secondary_id

205203

Identifier Type: REGISTRY

Identifier Source: secondary_id

2022-501966-23

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1282-6109

Identifier Type: OTHER

Identifier Source: secondary_id

2018-000669-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3475-716

Identifier Type: -

Identifier Source: org_study_id