AzTrials
AzTrials

MelanomaPhase 3NCT03553836

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

A Phase 3 study testing Pembrolizumab in people with Melanoma, run by Merck Sharp & Dohme LLC at 159 sites in 16 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Melanoma
What is being tested?
Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
976 participants
Where
159 sitesin 16 countries
Study dates
12 Sep 2018to 12 Oct 2033
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 17Show fewer
  • 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

Trial locations and contacts

159 sites in 16 countries.

159 sites in 16 countries

United States39 sites

  • Winship Cancer Institute of Emory University ( Site 0046)

    Atlanta, Georgia, 30322-1013

  • Northside Hospital ( Site 0115)

    Atlanta, Georgia, 30341

  • University of Colorado Cancer Center ( Site 0027)

    Aurora, Colorado, 80045

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

    Baltimore, Maryland, 21287

  • Massachusetts General Hospital ( Site 0126)

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center ( Site 0141)

    Boston, Massachusetts, 02215

  • Dana Farber Cancer Institute ( Site 0124)

    Boston, Massachusetts, 02215

  • Northwestern Medical Group ( Site 0135)

    Chicago, Illinois, 60611

  • The University of Chicago Medical Center ( Site 0007)

    Chicago, Illinois, 60637

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

    Cincinnati, Ohio, 45219

  • Karmanos Cancer Institute ( Site 0111)

    Detroit, Michigan, 48201

  • Inova Schar Cancer Institute ( Site 0014)

    Fairfax, Virginia, 22031

  • West Cancer Center - East Campus ( Site 0022)

    Germantown, Tennessee, 38138

  • Memorial Sloan Kettering ( Site 0006)

    Harrison, New York, 10604

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

    Houston, Texas, 77030

  • University of Iowa Hospital and Clinics ( Site 0001)

    Iowa City, Iowa, 52242

  • Mayo Clinic Florida ( Site 0024)

    Jacksonville, Florida, 32224

  • University of Tennessee Medical Center Knoxville ( Site 0116)

    Knoxville, Tennessee, 37920

  • UCSD Moores Cancer Center ( Site 0133)

    La Jolla, California, 92037

  • The Angeles Clinic and Research Institute ( Site 0029)

    Los Angeles, California, 90025

  • UCLA Hematology & Oncology ( Site 0130)

    Los Angeles, California, 90095

  • University of Wisconsin Hospital and Clinics ( Site 0030)

    Madison, Wisconsin, 53792

  • Yale University ( Site 0035)

    New Haven, Connecticut, 06511

  • Laura and Isaac Perlmutter Cancer Center ( Site 0137)

    New York, New York, 10016

  • Memorial Sloan Kettering Cancer Center ( Site 0142)

    New York, New York, 10022

  • Mount Sinai Medical Center ( Site 0038)

    New York, New York, 10029

  • Stephenson Cancer Center ( Site 0042)

    Oklahoma City, Oklahoma, 73104

  • Advocate Medical Group-Park Ridge ( Site 0025)

    Park Ridge, Illinois, 60068

  • Children's Hospital of Pittsburgh UPMC ( Site 0144)

    Pittsburgh, Pennsylvania, 15224

  • UPMC Hillman Cancer Centers ( Site 0043)

    Pittsburgh, Pennsylvania, 15232

  • Oregon Health & Science University ( Site 0032)

    Portland, Oregon, 97239

  • VCU Massey Cancer Center ( Site 0008)

    Richmond, Virginia, 23298

  • Mayo Clinic [Rochester, MN] ( Site 0016)

    Rochester, Minnesota, 55905

  • University of Rochester ( Site 0019)

    Rochester, New York, 14642

  • John Wayne Cancer Institute ( Site 0026)

    Santa Monica, California, 90404

  • Seattle Cancer Care Alliance ( Site 0044)

    Seattle, Washington, 98109

  • Siteman Cancer Center ( Site 0143)

    St Louis, Missouri, 63110

  • Moffitt McKinley Outpatient Center ( Site 0131)

    Tampa, Florida, 33612

  • University of Arizona Cancer Center ( Site 0121)

    Tucson, Arizona, 85719

Other trials in United States

France14 sites

  • CHU Amiens Picardie Hopital Nord ( Site 0317)

    Amiens, Somme, 80054

  • CHU Angers ( Site 0321)

    Angers, Maine-et-Loire, 49933

  • CHU de Bordeaux- Hopital Saint Andre ( Site 0304)

    Bordeaux, Gironde, 33075

  • Hopital Ambroise Pare Boulogne ( Site 0316)

    Boulogne-Billancourt, Hauts-de-Seine, 92100

  • CHU Dijon Bourgogne ( Site 0320)

    Dijon, Cote-d Or, 21000

  • CHRU Lille - Hopital Claude Huriez ( Site 0301)

    Lille, Nord, 59037

  • Hopital La Timone ( Site 0302)

    Marseille, Bouches-du-Rhone, 13385

  • CHU Montpellier. ( Site 0312)

    Montpellier, Herault, 34295

  • Hopital Saint Louis ( Site 0322)

    Paris, 75475

  • C.H.U. Lyon Sud ( Site 0303)

    Pierre-Bénite, Rhone, 69495

  • CHU de Reims ( Site 0307)

    Reims, Marne, 51100

  • Centre Eugene Marquis ( Site 0305)

    Rennes, Ille-et-Vilaine, 35042

  • Institut Claudius Regaud IUCT Oncopole ( Site 0306)

    Toulouse, Haute-Garonne, 31059

  • Institut Gustave Roussy ( Site 0300)

    Villejuif, Val-de-Marne, 94805

Other trials in France

Germany11 sites

  • Elbe Klinikum Buxtehude ( Site 0354)

    Buxtehude, Lower Saxony, 21614

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

    Essen, North Rhine-Westphalia, 45147

  • SRH Wald-Klinikum Gera GmbH ( Site 0360)

    Gera, Thuringia, 07548

  • Universitaetsklinikum Hamburg Eppendorf (UKE) ( Site 0352)

    Hamburg, 20246

  • Medizinische Hochschule Hannover ( Site 0358)

    Hanover, Lower Saxony, 30625

  • Universitaetsklinikum Schleswig-Holstein Campus Kiel ( Site 0359)

    Kiel, Schleswig-Holstein, 24105

  • Universitaetsklinikum in Mannheim ( Site 0351)

    Mannheim, Baden-Wurttemberg, 68135

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

    Munich, Bavaria, 80337

  • Klinikum Nuernberg Nord ( Site 0355)

    Nuremberg, Bavaria, 90419

  • Universitaetsklinikum Tuebingen ( Site 0353)

    Tübingen, Baden-Wurttemberg, 72076

  • Klinikum der Universitaet in Wuerzburg ( Site 0356)

    Würzburg, Bavaria, 97080

Other trials in Germany

Brazil10 sites

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

    Barretos, São Paulo, 14784-400

  • Hospital Erasto Gaertner ( Site 0159)

    Curitiba, Paraná, 81520-060

  • Hospital de Caridade de Ijui ( Site 0156)

    Ijuí, Rio Grande do Sul, 98700 000

  • Hospital Sao Vicente de Paulo ( Site 0158)

    Passo Fundo, Rio Grande do Sul, 99010-080

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

    Porto Alegre, Rio Grande do Sul, 90610-000

  • Instituto Nacional do Cancer II ( Site 0160)

    Rio de Janeiro, 20220-410

  • Hospital de Clinicas de Rio Preto ( Site 0162)

    Sao Jose Do Rio Preto - SP, São Paulo, 15090-000

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

    São Paulo, 01246-000

  • Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 0161)

    São Paulo, 01321-001

  • A.C. Camargo Cancer Center ( Site 0164)

    São Paulo, 01508-010

Other trials in Brazil

Canada10 sites

  • Cross Cancer Institute ( Site 0057)

    Edmonton, Alberta, T6G 1Z2

  • Moncton Hospital - Horizon Health Network ( Site 0055)

    Moncton, New Brunswick, E1C 6Z8

  • Hopital Maisonneuve Rosemont ( Site 0056)

    Montreal, Quebec, H1T 2M4

  • Jewish General Hospital ( Site 0054)

    Montreal, Quebec, H3T 1E2

  • McGill University Health Centre ( Site 0062)

    Montreal, Quebec, H4A 3J1

  • The Ottawa Hospital ( Site 0058)

    Ottawa, Ontario, K1H 8L6

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

    Québec, Quebec, G1R 2J6

  • Sunnybrook Research Institute ( Site 0060)

    Toronto, Ontario, M4N 3M5

  • Princess Margaret Cancer Centre ( Site 0059)

    Toronto, Ontario, M5G 2M9

  • CancerCare Manitoba ( Site 0053)

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Poland10 sites

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

    Bielsko-Biala, Silesian Voivodeship, 43-300

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

    Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796

  • Uniwersyteckie Centrum Kliniczne ( Site 0770)

    Gdansk, Pomeranian Voivodeship, 80-402

  • Uniwersyteckie Centrum Kliniczne Slaskiego Uniwersytetu Medycznego ( Site 0757)

    Katowice, Silesian Voivodeship, 40-514

  • Pratia MCM Krakow ( Site 0773)

    Krakow, Lesser Poland Voivodeship, 30-510

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

    Poznan, Greater Poland Voivodeship, 60-780

  • LIFTMED ( Site 0765)

    Rybnik, Silesian Voivodeship, 44-200

  • Kliniczny Szpital Wojewodzki Nr 1 ( Site 0758)

    Rzeszów, Podkarpackie Voivodeship, 35-055

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

    Warsaw, Masovian Voivodeship, 02-781

  • Instytut Pomnik Centrum Zdrowia Dziecka ( Site 0759)

    Warsaw, Masovian Voivodeship, 04-730

Other trials in Poland

Australia9 sites

  • Royal Adelaide Hospital ( Site 0861)

    Adelaide, South Australia, 5000

  • Cairns Base Hospital ( Site 0859)

    Cairns, Queensland, 4870

  • Ashford Cancer Centre Research ( Site 0860)

    Kurralta Park, South Australia, 5037

  • The Alfred Hospital ( Site 0852)

    Melbourne, Victoria, 3004

  • Fiona Stanley Hospital ( Site 0851)

    Murdoch, Western Australia, 6150

  • Melanoma Institute Australia ( Site 0856)

    North Sydney, New South Wales, 2065

  • Tasman Oncology Research Pty Ltd ( Site 0858)

    Southport, Queensland, 4215

  • Westmead Hospital ( Site 0853)

    Westmead, New South Wales, 2145

  • Princess Alexandra Hospital ( Site 0857)

    Woolloongabba, Queensland, 4102

Other trials in Australia

Italy9 sites

  • IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 0406)

    Bari, 70124

  • ASST Papa Giovanni XXIII ( Site 0402)

    Bergamo, 24127

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

    Genova, 16132

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

    Meldola, Forli-Cesena, 47014

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

    Milan, 20133

  • Istituto Nazionale Tumori Fondazione Pascale ( Site 0400)

    Naples, 80131

  • IRCCS Istituto Oncologico Veneto ( Site 0407)

    Padova, 35128

  • IDI - Istituto Dermopatico dell'Immacolata ( Site 0405)

    Roma, 00167

  • Azienda Ospedaliero Universitaria Senese ( Site 0401)

    Siena, 53100

Other trials in Italy

Switzerland9 sites

  • Universitaetsspital Basel ( Site 0554)

    Basel, Canton of Basel-City, 4031

  • Oncological Institute of Southern Switzerland ( Site 0557)

    Bellinzona, Canton Ticino, 6500

  • Universitaetsspital Bern ( Site 0552)

    Bern, Canton of Bern, 3010

  • Kantonsspital Graubuenden ( Site 0555)

    Chur, Kanton Graubünden, 7000

  • Hopitaux Universitaires de Geneve HUG ( Site 0556)

    Geneva, Canton of Geneva, 1211

  • Centre Hospitalier Universitaire Vaudois ( Site 0553)

    Lausanne, Canton of Vaud, 1011

  • Kantonsspital St. Gallen ( Site 0559)

    Sankt Gallen, Canton of St. Gallen, 9007

  • Hopital du Valais ( Site 0558)

    Sion, Valais, 1951

  • Universitaetsspital Zuerich ( Site 0551)

    Zurich, Canton of Zurich, 8091

Other trials in Switzerland

Israel7 sites

  • HaEmek Medical Center ( Site 0655)

    Afula, 1834111

  • Soroka Medical Center ( Site 0653)

    Beersheba, Southern District, 8457108

  • Rambam Medical Center ( Site 0654)

    Haifa, 3109601

  • Hadassah Ein Kerem Medical Center ( Site 0651)

    Jerusalem, 9112001

  • Chaim Sheba Medical Center. ( Site 0652)

    Ramat Gan, 5262000

  • Sourasky Medical Center ( Site 0656)

    Tel Aviv, Tell Abib, 6423906

  • Shamir Medical Center-Assaf Harofeh ( Site 0657)

    Tsrifin, 70300

Other trials in Israel

South Africa7 sites

  • Cancercare ( Site 0810)

    Cape Town, Limpopo, 7700

  • Sandton Oncology Medical Group PTY LTD ( Site 0801)

    Johannesburg, Gauteng, 2196

  • Cape Town Oncology Trials Pty Ltd ( Site 0807)

    Kraaifontein, Western Cape, 7570

  • Charlotte Maxeke Johannesburg Academic Hospital ( Site 0811)

    Parktown, Gauteng, 2196

  • Cancer Care Langenhoven Drive Oncology Centre ( Site 0812)

    Port Elizabeth, Eastern Cape, 6045

  • Wilgers Oncology Centre ( Site 0806)

    Pretoria, Gauteng, 0081

  • MPOC ( Site 0803)

    Pretoria, Gauteng, 0181

Other trials in South Africa

Belgium6 sites

  • Institut Jules Bordet ( Site 0254)

    Brussels, Bruxelles-Capitale, Region de, 1000

  • Cliniques Universitaires Saint-Luc ( Site 0251)

    Brussels, Bruxelles-Capitale, Region de, 1200

  • UZ Gent ( Site 0255)

    Ghent, Oost-Vlaanderen, 9000

  • Jessa Ziekenhuis Campus Virga Jesse ( Site 0256)

    Hasselt, Limburg, 3500

  • UZ Leuven ( Site 0252)

    Leuven, Vlaams-Brabant, 3000

  • GZA Sint Augustinus ( Site 0259)

    Wilrijk - Antwerpen, Antwerpen, 2610

Other trials in Belgium

Chile6 sites

  • Centro Oncologico Antofagasta ( Site 0206)

    Antofagasta, 1240000

  • Fundacion Arturo Lopez Perez FALP ( Site 0200)

    Santiago, Region M. de Santiago, 7500921

  • Pontificia Universidad Catolica de Chile ( Site 0201)

    Santiago, Region M. de Santiago, 8330032

  • Sociedad Medica Aren y Bachero Limitada ( Site 0207)

    Santiago, Region M. de Santiago, 8420383

  • Instituto Clinico Oncologico del Sur ( Site 0203)

    Temuco, Araucania, 4810469

  • Oncocentro ( Site 0204)

    Viña del Mar, Valparaiso, 2520598

Other trials in Chile

Spain6 sites

  • Hospital General Universitari Vall d Hebron ( Site 0456)

    Barcelona, 08035

  • Hospital Clinic de Barcelona ( Site 0452)

    Barcelona, 08036

  • Onkologikoa - Instituto Oncologico de San Sebastian ( Site 0457)

    Donostia / San Sebastian, Gipuzkoa, 20014

  • Hospital General Universitario Gregorio Maranon ( Site 0454)

    Madrid, 28009

  • Hospital Universitario Virgen Macarena ( Site 0455)

    Seville, 41009

  • Hospital General Universitario de Valencia ( Site 0451)

    Valencia, Valenciana, Comunitat, 46014

Other trials in Spain

United Kingdom5 sites

  • Addenbrooke's Hospital in Cambridge ( Site 0600)

    Cambridge, Cambridgeshire, CB2 0QQ

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

    London, London, City of, SE1 9RT

  • Royal Marsden Hospital - Fulham Road London ( Site 0613)

    London, London, City of, SW3 6JJ

  • Christie NHS Foundation Trust ( Site 0604)

    Manchester, M20 4GJ

  • The Royal Marsden NHS Foundation Trust. ( Site 0612)

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

Japan1 site

  • National Cancer Center Hospital ( Site 0910)

    Tokyo, 104-0045

Other trials in Japan

About this study

Official title: 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.

Conditions
Melanoma
Being tested
Pembrolizumab, Placebo
Keywords
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)
Medical subject headings
Melanoma, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabBiological

    Also called KEYTRUDA®, MK-3475

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

  • PlaceboOther

    Administered as an IV infusion every 3 weeks (Q3W)

Study groups in NCT03553836
Study groupRoleWhat they receive
PembrolizumabExperimentalParticipants 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.
Receives: Biological: Pembrolizumab
PlaceboPlacebo comparatorParticipants 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.
Receives: Biological: Pembrolizumab; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to ~32.7 months

Secondary outcomes (4)

  1. 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.

    Measured: Up to ~9 years

  2. 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.

    Measured: Up to ~15 years

  3. 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.

    Measured: Up to ~19.3 months

  4. 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.

    Measured: Up to ~19.3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jun 2018
  2. Study start12 Sep 2018
  3. Primary completion21 Jun 2021
  4. Study completion12 Oct 2033 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
976 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03553836
Sponsor's protocol ID
3475-716
Other IDs
MK-3475-716, KEYNOTE-716, 205203, 2022-501966-23, U1111-1282-6109, 2018-000669-35, 2018
Status last verified
Nov 2024
First submitted
1 Jun 2018
Last updated
29 Nov 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • 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.

    PubMed 38452313

  • Leachman SA, Luke JJ, Ascierto PA, Long GV, Khattak MA, Rutkowski P, Xu ZJ, Fukunaga-Kalabis M, Krepler C, Eggermont AMM, Schadendorf D. Adjuvant Pembrolizumab for Stage IIB or IIC Melanoma: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2026 Feb 2;9(2):e2559603. doi: 10.1001/jamanetworkopen.2025.59603.

    PubMed 41701495

  • 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.

    PubMed 40198940

  • 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.

    PubMed 40078077

  • 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.

    PubMed 38485189

  • 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.

    PubMed 36748342

  • 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.

    PubMed 36265502

  • 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.

    PubMed 35367007

  • 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.

    PubMed 31870188

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pembrolizumab in people with Melanoma, run by Merck Sharp & Dohme LLC at 159 sites in 16 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 29 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 159 sites in United States, France, Germany, Brazil, Canada and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recurrence-free Survival (RFS) (time frame: Up to ~32.7 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03553836, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in