High-risk Non-muscle Invasive Bladder CancerPhase 3NCT03711032
Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Bacillus Calmette-Guerin (BCG) in High-Risk Non-Muscle Invasive Bladder Cancer (HR NMIBC) (MK-3475-676/KEYNOTE-676)
A Phase 3 study testing Pembrolizumab and BCG in people with High-risk Non-muscle Invasive Bladder Cancer, run by Merck Sharp & Dohme LLC at 209 sites in 30 countries.
Trial summary
Researchers are looking for new ways to treat high-risk non muscle invasive bladder cancer (HR NMIBC). NMIBC is cancer in the tissue that lines the inside of the bladder but has not spread to the bladder muscle or outside of the bladder. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High-risk Non-muscle Invasive Bladder Cancer
- What is being tested?
- Pembrolizumab and BCG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,397 participants
- Where
- 209 sitesin 30 countries
- Study dates
- 24 Dec 2018to 20 Nov 2034
- Phase
- Phase 3
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have locally and blinded independent central review (BICR)-confirmed histological diagnosis of high-risk non-muscle invasive (T1, high grade Ta and/or CIS) UC of the bladder
- Has undergone cystoscopy/ transurethral resection of bladder tumor (TURBT) to remove all resectable disease
- Has provided tissue for biomarker analysis
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- Has adequate organ function
- During the treatment period and for ≥7 days after the last dose of BCG, male participants are EITHER abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR, must agree to use contraception unless confirmed to be azoospermic
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- Female participants who are not pregnant, not breastfeeding, and either not a woman of child bearing potential (WOCBP); or are a WOCBP who agrees to use a contraception method that is highly effective or remains abstinent from heterosexual intercourse during the treatment period and for ≥7 days after the last dose of BCG or 120 days after the last dose of pembrolizumab, whichever comes last
- BCG Post-induction Cohort (Cohort A) Only
- Has been treated with one adequate course of BCG induction therapy for the treatment of HR NMIBC
- Following adequate BCG induction therapy, must have persistent or recurrent HR NMIBC
Who cannot join
- Has a history of or concurrent locally advanced (i.e., T2, T3, T4) or metastatic UC
- Has concurrent extra-vesical (i.e, urethra, ureter, renal pelvis) non-muscle invasive urothelial carcinoma or a history of extra-vesical non-muscle invasive UC
- Has received prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks of start 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 of start of study treatment
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of start of study treatment
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- Has a known additional malignancy that is progressing or requires active treatment within the past 3 years
- Has an active autoimmune disease that has required systemic treatment in past 2 years
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- Has one or more of the following contraindications to BCG: prior BCG sepsis or systemic infection, total bladder incontinence, or an adverse experience to a previous BCG instillation that resulted in treatment discontinuation and precludes retreating with BCG
- Has an active infection or diagnosis requiring systemic antimicrobial therapy
- Has a known history of human immunodeficiency virus (HIV) infection
- Has a known history of Hepatitis B or known active Hepatitis C virus infection
- Has current active tuberculosis
- Has had an allogenic-tissue/solid organ transplant
- Has any contraindication(s) to IV contrast or is otherwise unable to have screening imaging with IV contrast performed
- BCG Post-induction Cohort (Cohort A) Only - Has persistent T1 disease following an induction course of BCG
- BCG Naïve Cohort (Cohort B) Only
- Has received any prior treatment with BCG for their NMIBC within the past 2 years prior to study entry
Trial locations and contacts
209 sites in 30 countries.
209 sites in 30 countries
United States44 sites
St. Peter's Hospital Cancer Care Center ( Site 1087)
Albany, New York, 12208
Alaska Urological Institute dba Alaska Clinical Research Center ( Site 1083)
Anchorage, Alaska, 99503
Emory School of Medicine ( Site 1076)
Atlanta, Georgia, 30322
MidLantic Urology ( Site 1071)
Bala-Cynwyd, Pennsylvania, 19004
Coastal Urology Associates ( Site 1055)
Brick, New Jersey, 08724
University of Vermont Medical Center ( Site 1057)
Burlington, Vermont, 05401
Northwestern Memorial Hospital ( Site 1101)
Chicago, Illinois, 60611
TriState Urologic Services PSC Inc. dba The Urology Group ( Site 1091)
Cincinnati, Ohio, 45212
University Hospitals Cleveland Medical Center ( Site 1066)
Cleveland, Ohio, 44106
Ohio State University Arthur G James Cancer Hospital & Richard J Solove Research Institute ( Site 1067)
Columbus, Ohio, 43210
Urology Clinics of North Texas, PLLC ( Site 1064)
Dallas, Texas, 75231
University Of Texas Southwestern Medical Center ( Site 1053)
Dallas, Texas, 75390
Henry Ford Hospital ( Site 1062)
Detroit, Michigan, 48202
Texas Oncology-Fort Worth Cancer Center ( Site 8003)
Fort Worth, Texas, 76104
Urological Research Network ( Site 1106)
Hialeah, Florida, 33016
Houston Metro Urology ( Site 1111)
Houston, Texas, 77027
Mayo Clinic in Florida-Urology ( Site 1097)
Jacksonville, Florida, 32224
R.J. Zuckerberg Cancer Center ( Site 1080)
Lake Success, New York, 11042
Colorado Clinical Research ( Site 1100)
Lakewood, Colorado, 80228
Lancaster Urology ( Site 1079)
Lancaster, Pennsylvania, 17604
UCLA Hematology/Oncology - Westwood (Building 200 Suite 140)-Department of Urology/Institute of Uro ( Site 1052)
Los Angeles, California, 90095
University of Miami Hospital and Clinics, Sylvester Cancer Center ( Site 1056)
Miami, Florida, 33136
Morristown Medical Center ( Site 1090)
Morristown, New Jersey, 07960
Carolina Urologic Research Center ( Site 1085)
Myrtle Beach, South Carolina, 29572
Urology Associates [Nashville, TN] ( Site 1072)
Nashville, Tennessee, 37209
Rutgers Cancer Institute of New Jersey ( Site 1059)
New Brunswick, New Jersey, 08901
Veterans Affairs New York Harbor Healthcare System-PCF COE ( Site 1112)
New York, New York, 10010
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 1074)
New York, New York, 10016
University of California Irvine Medical Center ( Site 1061)
Orange, California, 92868
Woodlands Medical Specialists, PA ( Site 8002)
Pensacola, Florida, 32503
University of Pennsylvania ( Site 1088)
Philadelphia, Pennsylvania, 19104
Mayo Clinic in Arizona - Phoenix ( Site 1094)
Phoenix, Arizona, 85054
Texas Oncology-Plano West ( Site 8001)
Plano, Texas, 75093
OHSU Knight Cancer Institute ( Site 1075)
Portland, Oregon, 97210
Advanced Urology ( Site 1092)
Roswell, Georgia, 30076
Urology San Antonio Research ( Site 1108)
San Antonio, Texas, 78229
Ochsner LSU Health Shreveport - Regional Urology ( Site 1099)
Shreveport, Louisiana, 71106
Oregon Urology Institute ( Site 1098)
Springfield, Oregon, 97477
Associated Medical Professionals of NY ( Site 1078)
Syracuse, New York, 13210
Genesis Research LLC ( Site 1065)
Torrance, California, 90505
Michigan Institute of Urology ( Site 1077)
Troy, Michigan, 48084
Del Sol Research Management, LLC ( Site 1096)
Tucson, Arizona, 85715
Urology of Virginia ( Site 1070)
Virginia Beach, Virginia, 23462
Wichita Urology Group ( Site 1086)
Wichita, Kansas, 67226
China21 sites
Cancer Hospital Chinese Academy of Medical Science-Urinary Surgery ( Site 1766)
Beijing, Beijing Municipality, 100021
Peking University First Hospital ( Site 1759)
Beijing, Beijing Municipality, 100034
Beijing Cancer hospital-Urinary Surgery ( Site 1755)
Beijing, Beijing Municipality, 100142
Hunan Cancer Hospital ( Site 1763)
Changsha, Hunan, 410013
West China Hospital Sichuan University ( Site 1767)
Chengdu, Sichuan, 610041
Chongqing University Cancer Hospital ( Site 1784)
Chongqing, Chongqing Municipality, 400030
SUN YAT-SEN UNIVERSITY CANCER CENTRE ( Site 1752)
Guangzhou, Guangdong, 510060
The First Affiliated Hospital of Guangzhou Medical University ( Site 1777)
Guangzhou, Guangdong, 510120
Sun Yat-sen Memorial Hospital, Sun Yat-sen University-Urology Surgery ( Site 1751)
Guangzhou, Guangdong, 510289
Zhejiang Provincial People's Hospital-Urology ( Site 1762)
Hangzhou, Zhejiang, 310014
Harbin Medical University Cancer Hospital ( Site 1772)
Harbin, Heilongjiang, 150000
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School-Urology ( Site 1758)
Nanjing, Jiangsu, 210008
ShenZhen People's Hospital ( Site 1778)
Shenzhen, Guangdong, 518020
The Second Affiliated Hospital of Soochow University-Urology ( Site 1773)
Suzhou, Jiangsu, 215004
The Second Hospital of Tianjin Medical University ( Site 1769)
Tianjin, Tianjin Municipality, 300211
The First Affiliated Hospital of Wenzhou Medical University-Urology Surgery ( Site 1774)
Wenzhou, Zhejiang, 325000
Tongji Hospital Tongji Medical,Science & Technology ( Site 1768)
Wuhan, Hubei, 430000
Wuhan Union Hospital ( Site 1771)
Wuhan, Hubei, 430022
The First Affiliated Hospital of Xi'an Jiaotong University ( Site 1764)
Xi'an, Shaanxi, 710061
The First Affiliated hospital of Xiamen University-Urology ( Site 1776)
Xiamen, Fujian, 361003
Henan Cancer Hospital-Urology ( Site 1770)
Zhengzhou, Henan, 450008
Japan14 sites
Chiba Cancer Center ( Site 0401)
Chiba, 260-8717
Harasanshin Hospital ( Site 0410)
Fukuoka, 812-0033
Hamamatsu University Hospital ( Site 0416)
Hamamatsu, Shizuoka, 431-3192
Hirosaki University Hospital ( Site 0407)
Hirosaki, Aomori, 036-8563
Nara Medical University Hospital ( Site 0411)
Kashihara, Nara, 634-8522
St. Marianna University Hospital ( Site 0415)
Kawasaki, Kanagawa, 216-8511
Osaka Prefectural Hospital Organization Osaka International Cancer Institute ( Site 0413)
Osaka, 541-8567
Osaka Metropolitan University Hospital ( Site 0404)
Osaka, 545-8586
Kitasato University Hospital ( Site 0403)
Sagamihara, Kanagawa, 252-0375
Institute of Science Tokyo Hospital ( Site 0409)
Tokyo, 113-8519
Keio University Hospital ( Site 0405)
Tokyo, 160-8582
Ehime University Hospital ( Site 0414)
Tōon, Ehime, 791-0295
University of Tsukuba Hospital ( Site 0412)
Tsukuba, Ibaraki, 305-8576
Yokosuka Kyosai Hospital ( Site 0406)
Yokosuka, Kanagawa, 238-8558
Italy12 sites
Azienda USL 8 di Arezzo-Medical Oncology ( Site 0363)
Arezzo, 52100
Istituto Tumori Giovanni Paolo II ( Site 0357)
Bari, 70124
Osp Generale Reg di Bolzano ( Site 0355)
Bolzano, Trentino-Alto Adige, 39100
Ospedale Clinicizzato Santissima Annunziata ( Site 0361)
Chieti, Abruzzo, 66100
Azienda Ospedaliero Universitaria Careggi ( Site 0360)
Florence, Tuscany, 50134
Ospedale San Martino ( Site 0351)
Genova, 16132
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0353)
Milan, Milano, 20133
IRCCS Ospedale San Raffaele ( Site 0362)
Milan, 20132
Ospedale Buccheri La Ferla Fatebenefratelli ( Site 0352)
Palermo, 90123
Policlinico Universitario A. Gemelli ( Site 0358)
Roma, 00168
Ospedale Mauriziano-SCDU ONCOLOGIA MEDICA ( Site 0366)
Turin, Piedmont, 10128
A.O.U. di Verona - Ospedale Civile Maggiore Borgo Trento ( Site 0356)
Verona, 37126
Poland12 sites
Szpital Specjalistyczny w Koscierzynie Sp. z o.o. ( Site 0671)
Kościerzyna, Pomeranian Voivodeship, 83-400
Pratia MCM Krakow ( Site 0668)
Krakow, Lesser Poland Voivodeship, 30-510
Clinical Research Center Sp. z o.o. ( Site 0674)
Poznan, Greater Poland Voivodeship, 61-731
Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 0678)
Przemyśl, Podkarpackie Voivodeship, 37-700
LIFTMED ( Site 0652)
Rybnik, Silesian Voivodeship, 44-200
Urologica Praktyka Lekarska Adam Marcheluk ( Site 0654)
Siedlce, Masovian Voivodeship, 08-110
Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku ( Site 0655)
Słupsk, Pomeranian Voivodeship, 76-200
Szpital Wojewódzki im. Świętego Lukasza SP ZOZ w Tarnowie ( Site 0681)
Tarnów, Lesser Poland Voivodeship, 33-100
MICS Centrum Medyczne Torun ( Site 0679)
Torun, Kuyavian-Pomeranian Voivodeship, 87-100
Luxmed Onkologia sp. z o. o. ( Site 0653)
Warsaw, Masovian Voivodeship, 01-748
Medical Concierge Centrum Medyczne ( Site 0676)
Warsaw, Masovian Voivodeship, 02-798
Uniwesytecki Szpital Kliniczny we Wroclawiu ( Site 0669)
Wroclaw, Lower Silesian Voivodeship, 50-556
Spain10 sites
Fundacio Puigvert ( Site 0864)
Barcelona, 08025
Hospital Universitario Lucus Augusti ( Site 0852)
Lugo, La Coruna, 27003
Hospital Universitario Gregorio Maranon ( Site 0854)
Madrid, 28009
Clinica Universitaria Navarra - Madrid ( Site 0860)
Madrid, 28027
MD Anderson Cancer Center Madrid ( Site 0859)
Madrid, 28033
Hospital Universitario Ramon y Cajal ( Site 0857)
Madrid, 28034
Hospital Universitario La Paz ( Site 0866)
Madrid, 28046
Clinica Universitaria de Navarra ( Site 0863)
Pamplona, Navarre, 31008
Hospital Universitario Quiron Madrid ( Site 0862)
Pozuelo de Alarcón, Madrid, Comunidad de, 28223
Hospital La Fe de Valencia ( Site 0855)
Valencia, 46026
Canada8 sites
Exdeo Clinical Research Inc. ( Site 0165)
Abbotsford British Columbia, British Columbia, V2T 1X8
CIUSSS du Saguenay-Lac-St-Jean ( Site 0164)
Chicoutimi, Quebec, G7H 5H6
Horizon Health Network ( Site 0160)
Moncton, New Brunswick, E1C 6Z8
CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0157)
Montreal, Quebec, H1T 2M4
Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0151)
Québec, Quebec, G1J 1Z4
CHUS - Hopital Fleurimont ( Site 0152)
Sherbrooke, Quebec, J1H 5N4
Princess Margaret Cancer Centre ( Site 0153)
Toronto, Ontario, M5G 2M9
Silverado Resarch Inc. ( Site 0155)
Victoria, British Columbia, V8T 2C1
Colombia8 sites
Administradora Country S.A. - Clinica del Country ( Site 1607)
Bogotá, Bogota D.C., 110221
Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 1605)
Bogotá, Bogota D.C., 111321
Hemato Oncologos SA-Oncology ( Site 1601)
Cali, Valle del Cauca Department, 76001
Clínica Imbanaco S.A.S ( Site 1611)
Cali, Valle del Cauca Department, 760042
Instituto de Cancerología-Oncology ( Site 1609)
Medellín, Antioquia, 050024
IMAT S.A.S ( Site 1604)
Montería, Departamento de Córdoba, 230002
Oncologos del Occidente ( Site 1608)
Pereira, Risaralda Department, 661001
Fundación Hospital San Vicente de Paúl - Rionegro - Centros Especializados o de Centros Especializad ( Site 1606)
Rionegro, Antioquia, 054047
Brazil6 sites
Fundação Pio XII - Hospital de Câncer de Barretos-Unidade de Pesquisa Clínica ( Site 1553)
Barretos, São Paulo, 14784-400
Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 1551)
Curitiba, Paraná, 81520-060
Hospital São Carlos-Oncocentro Ce ( Site 1558)
Fortaleza, Ceará, 60135-237
ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 1560)
São Paulo, 01246-000
BP - A Beneficencia Portuguesa de São Paulo ( Site 1559)
São Paulo, 01321-001
Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 1554)
São Paulo, 04014-002
Portugal6 sites
Unidade Local de Saude de Braga - Hospital de Braga ( Site 0705)
Braga, 4710-243
Inst. Portugues de Oncologia de Coimbra Francisco Gentil EPE ( Site 0704)
Coimbra, 3000-075
Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE ( Site 0708)
Lisbon, 1099-023
Unidade Local de Saude de Santa Maria - Hospital de Santa Maria ( Site 0702)
Lisbon, 1649-035
Hospital CUF Descobertas ( Site 0706)
Lisbon, 1998-018
Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 0701)
Porto, 4200-072
Turkey (Türkiye)6 sites
Ankara Universitesi Tip Fakultesi Hastanesi ( Site 0966)
Ankara, 06590
Eskisehir Osmangazi Universitesi Hastanesi ( Site 0953)
Eskişehir, 26480
Memorial Sisli Hastanesi-Medical Oncology ( Site 0965)
Istanbul, 34385
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 0963)
Istanbul, 34722
Dokuz Eylul Universitesi ( Site 0959)
Izmir, 35340
Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 0961)
Konya, 42000
Belgium5 sites
AZORG Campus Aalst-Moorselbaan ( Site 0106)
Aalst, Oost-Vlaanderen, 9300
UZA University Hospital Antwerp ( Site 0105)
Edegem, Antwerpen, 2650
AZ Maria Middelares Gent ( Site 0102)
Ghent, Oost-Vlaanderen, 9000
UZ Gent ( Site 0101)
Ghent, Oost-Vlaanderen, 9000
CHU UCL Namur Site de Godinne ( Site 0103)
Yvoir, Namur, 5530
France5 sites
HENRI MONDOR HOSPITAL ( Site 1357)
Créteil, Seine-et-Marne, 94000
Centre Hospitalier Universitaire Dijon Bourgogne - Hôpital François Mitterrand-Urology ( Site 1355)
Dijon, Bourgogne-Franche-Comté, 21000
Hopital Claude Huriez - CHU de Lille ( Site 1360)
Lille, Nord, 59037
Centre Hospitalier Universitaire de Rennes - Hôpital Pontchaillou ( Site 1353)
Rennes, Brittany Region, 35000
Hôpital Foch-Urology department ( Site 1351)
Suresnes, Hauts-de-Seine, 92150
Germany5 sites
Universitaetsklinikum Jena ( Site 0252)
Jena, Thuringia, 07747
Klinikum Rechts der Isar. Technischen Universitaet Muenchen ( Site 0266)
Munich, Bavaria, 81675
Krankenhaus der Barmherzigen Brüder Trier-Abteilung für Urologie und Kinderurologie ( Site 0262)
Trier, Rhineland-Palatinate, 54292
Klinikum Weiden ( Site 0259)
Weiden in Der Oberpfalz, Bavaria, 92637
Universitaetsklinikum Wuerzburg ( Site 0265)
Würzburg, Bavaria, 97080
Greece5 sites
ATTIKON GENERAL UNIVERSITY HOSPITAL ( Site 0304)
Chaïdári, Attica, 124 62
University Hospital of Larissa ( Site 0301)
Larissa, Thessaly, 411 10
Olympion General Clinic ( Site 0306)
Pátrai, Achaia, 264 43
General University Hospital of Patras ( Site 0302)
Pátrai, Achaia, 265 04
Antikarkiniko Nosokomeio Thessalonikis THEAGENIO ( Site 0303)
Thessaloniki, Central Macedonia, 54007
Australia4 sites
Epworth Hospital ( Site 0009)
Richmond, Victoria, 3121
GenesisCare North Shore ( Site 0010)
St Leonards, New South Wales, 2065
Northern Cancer Institute. ( Site 0003)
St Leonards, New South Wales, 2065
Sydney Adventist Hospital ( Site 0001)
Wahroonga, New South Wales, 2076
Austria4 sites
Univ. Klinik f. Urologie Innsbruck ( Site 0051)
Innsbruck, Tyrol, 6020
Ordensklinikum Linz GmbH Elisabethinen ( Site 0052)
Linz, Upper Austria, 4020
Universitaetsklinik Salzburg ( Site 0053)
Salzburg, 5020
Medizinische Universität Wien ( Site 0054)
Vienna, State of Vienna, 1090
Hungary4 sites
Semmelweis University-Urológiai Klinika ( Site 1301)
Budapest, 1082
Debreceni Egyetem Klinikai Kozpont ( Site 1302)
Debrecen, 4032
Pécsi Tudományegyetem Klinikai Központ-Urológiai Klinika ( Site 1304)
Pécs, Baranya, 7621
Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ-Urológiai Klinika ( Site 1303)
Szeged, Csongrád megye, 6725
South Korea4 sites
Korea University Anam Hospital ( Site 0801)
Seoul, 02841
Seoul National University Hospital ( Site 0802)
Seoul, 03080
Samsung Medical Center ( Site 0803)
Seoul, 06351
Asan Medical Center ( Site 0804)
Songpagu, Seoul, 05505
Guatemala3 sites
INTEGRA Cancer Institute ( Site 1451)
Guatemala City, 01010
Onco Go, S.A ( Site 1454)
Guatemala City, 01010
Grupo Medico Angeles ( Site 1453)
Guatemala City, 01015
Netherlands3 sites
Maastricht University Medical Centre ( Site 0453)
Maastricht, Limburg, 6229 HX
Erasmus MC ( Site 0451)
Rotterdam, South Holland, 3015 GD
Universitair Medisch Centrum Utrecht-Medical Oncology ( Site 0455)
Utrecht, 3584 CX
Peru3 sites
Hospital Nacional Guillermo Almenara Irigoyen ( Site 0601)
La Victoria, Lima region, 15033
Oncosalud ( Site 0603)
Lima, Lima Province, 15036
Hospital Militar Central [Lima, Peru] ( Site 0604)
Lima, 15076
Switzerland3 sites
Universitaetsspital Basel ( Site 1201)
Basel, Canton of Basel-City, 4031
Hopitaux Universitaires de Geneve HUG ( Site 1204)
Geneva, 1205
Universitaetsspital Zurich ( Site 1203)
Zurich, 8091
Taiwan3 sites
China Medical University Hospital-Department of Urology ( Site 1654)
Taichung, 40447
Taichung Veterans General Hospital ( Site 1653)
Taichung, 407
Taipei Veterans General Hospital ( Site 1652)
Taipei, 112
United Kingdom3 sites
Raigmore Hospital ( Site 1006)
Inverness, Highland, IV2 3UJ
St Bartholomew s Hospital ( Site 1008)
London, London, City of, EC1A 7BE
St Georges University Hospitals NHS Foundation Trust. ( Site 1005)
London, London, City of, SW17 0QT
Costa Rica2 sites
CIMCA ( Site 1550)
San José, Provincia de San José, 10103
Policlinico San Bosco ( Site 0600)
San José, 10103
Norway2 sites
Akershus University Hospital ( Site 0553)
Lorenskog, Akershus, 1478
Stavanger universitetssykehus ( Site 0555)
Stavanger, Rogaland, 4011
Puerto Rico2 sites
Advance Urology and Laparoscopic Center ( Site 0757)
Ponce, 00716
Ad-Vance Medical Research ( Site 0756)
Ponce, 00717
Finland1 site
Tampere University Hospital [Tampere Finland] ( Site 0201)
Tampere, Pirkanmaa, 33520
Malaysia1 site
University Malaya Medical Centre ( Site 1180)
Kuala Lumpur, 59100
About this study
Official title: A Phase 3, Randomized, Comparator-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Bacillus Calmette-Guerin (BCG) in Participants With High-risk Non-muscle Invasive Bladder Cancer (HR NMIBC) That is Either Persistent or Recurrent Following BCG Induction or That is Naïve to BCG Treatment (KEYNOTE-676)
Researchers are looking for new ways to treat high-risk non muscle invasive bladder cancer (HR NMIBC). NMIBC is cancer in the tissue that lines the inside of the bladder but has not spread to the bladder muscle or outside of the bladder. High-risk means NMIBC may have a high chance of getting worse or coming back after treatment.
The goals of this study are to learn: 1. If more people who receive pembrolizumab with Bacillus Calmette-Guerin (BCG) have no signs of cancer in their body and live longer without the cancer growing, spreading, or coming back compared to people who receive BCG alone. 2. About the safety and how well people tolerate BCG alone or in combination with pembrolizumab.
- Being tested
- Pembrolizumab, BCG
- Keywords
- programmed cell death receptor 1 (PD-1), programmed cell death ligand 1 (PD-L1), anti-PD-1, anti-PD-L1, BCG, HR NMIBC, Patient Reported Outcome (PRO)
- Medical subject headings
- 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
Pembrolizumab IV infusion of 200 mg Q3W for BCG Post-Induction Cohort (Cohort A), or IV infusion of 400 mg Q6W for BCG Naïve Cohort (Cohort B), according to randomization
BCGBiological
Also called TICE® BCG, OncoTICE®
BCG (intravesical instillation): powder for instillation fluid for intravesical use, administered during Induction and Maintenance therapy
| Study group | Role | What they receive |
|---|---|---|
| BCG plus Pembrolizumab: Post-induction Cohort A (Arm A-1) | Experimental | Participants receive BCG (Induction and Maintenance) in combination with 200 mg pembrolizumab administered intravenously (IV) every 3 weeks (Q3W) for 35 doses (~2 years). Receives: Biological: Pembrolizumab; Biological: BCG |
| BCG Monotherapy: Post-induction Cohort A (Arm A-2) | Experimental | Participants receive BCG monotherapy (Induction and Maintenance). Receives: Biological: BCG |
| BCG plus Pembrolizumab: BCG Naïve Cohort B-Reduced Maintenance (Arm B-1) | Experimental | Participants receive BCG (Induction and reduced Maintenance) in combination with 400 mg pembrolizumab administered IV every 6 weeks (Q6W) for 9 doses (~1 year). Receives: Biological: Pembrolizumab; Biological: BCG |
| BCG plus Pembrolizumab: BCG Naïve Cohort B-Full Maintenance (Arm B-2) | Experimental | Participants receive BCG (Induction and full Maintenance) in combination with 400 mg pembrolizumab administered IV Q6W for 9 doses (~1 year). Receives: Biological: Pembrolizumab; Biological: BCG |
| BCG Monotherapy: BCG Naïve Cohort B (Arm B-3) | Experimental | Participants receive BCG monotherapy (Induction and Maintenance). Receives: Biological: BCG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Response Rate (CRR) by Blinded Independent Central Review (BICR) (Cohort A)
CRR is defined as the percentage of participants with carcinoma in situ (CIS) achieving a complete response (CR).
Measured: Up to ~3.5 years
Event-Free Survival (EFS) (Cohort B)
EFS is defined as the time from randomization until urothelial carcinoma (UC)-defined event, or death due to any cause.
Measured: Up to ~5 years
Secondary outcomes (18)
EFS (Cohort A)
EFS is defined as the time from randomization until UC-defined event, or death due to any cause.
Measured: Up to ~5 years
Recurrence-Free Survival (RFS) (Cohorts A and B)
RFS is defined as the time from randomization until the first occurrence of any UC recurrence, progression, or death due to any cause.
Measured: Up to ~5 years
Overall Survival (OS) (Cohorts A and B)
OS is defined as the time from randomization to death due to any cause.
Measured: Up to ~5 years
Disease Specific Survival (DSS) (Cohorts A and B)
DSS is defined as the time from randomization to death due to bladder cancer.
Measured: Up to ~5 years
Time to Cystectomy (Cohorts A and B)
Time to cystectomy is defined as the time from a participant's randomization until the date of cystectomy.
Measured: Up to ~5 years
12-Month EFS Rate (Cohort A)
EFS is defined as the time from randomization until UC-defined event, or death due to any cause. The 12-month EFS rate is defined as the percentage of participants with EFS at 12 months.
Measured: 12 months after EFS (up to ~5 years)
Duration of Response (DOR) (Cohorts A and B)
DOR in participants with CIS is defined as the time from first documented CR until end of response or death due to any cause, whichever occurs first.
Measured: Up to ~5 years
12-Month DOR Rate (Cohorts A and B)
The 12-month DOR Rate in participants with CIS is defined as the percentage of participants with a CR of at least 12 months duration.
Measured: 12 months after CR (up to ~4.5 years)
Percentage of Participants Experiencing Adverse Events (AEs) (Cohorts A and B)
An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Measured: Up to ~5 years
Percentage of Participants Discontinuing Study Drug Due to AEs (Cohorts A and B)
An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Measured: Up to ~5 years
Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Cohorts A and B)
The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall outcome. The change from baseline in Global Health Status/Quality of Life (EORTC QLQ-C30 Items 29 and 30) combined score will be presented.
Measured: Baseline, time of last PRO assessment (up to ~2 years)
Change from Baseline in EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score (Cohorts A and B)
EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better quality of life. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) combined score will be presented.
Measured: Baseline, time of last PRO assessment (up to ~2 years)
Change from Baseline in EORTC-QLQ-Non-muscle Invasive Bladder Cancer Module 24 (NMIBC24) Total Score (Cohorts A and B)
The EORTC-QLQ-NMIBC24 is a 24-item questionnaire developed to supplement the EORTC QLQ-C30 in high-risk NMIBC patients. Each item is scored out of 4 total points (1=Not at All to 4=Very Much). All responses are transformed from 0 to 100, with a high score indicating more symptoms or problems. The change from baseline in EORTC-QLQ-NMIBC24 total score will be presented.
Measured: Baseline, time of last PRO assessment (up to ~2 years)
Change from Baseline in European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS) (Cohorts A and B)
The EQ-5D-5L VAS records the respondent's self-rated health on a 10 cm vertical, visual analogue scale. It is rated by the respondent on a scale 0 to 100, with 0 being "the worst health you can imagine" and 100 being "the best health you can imagine". The change from baseline in EQ-5D-5L VAS will be presented.
Measured: Baseline, time of last PRO assessment (up to ~2 years)
Time to Deterioration (TTD) in the EORTC-QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Cohorts A and B)
EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall outcome. TTD in Global Health Status/Quality of Life is defined as the time from baseline to the first onset of a 10 point or greater decrease from baseline in the Global Health Status/Quality of Life (EORTC QLQ-C30 Items 29 and 30) combined score, with or without subsequent confirmation.
Measured: Time of last PRO assessment (up to ~2 years)
TTD in the EQ-5D-5L VAS (Cohorts A and B)
The EQ-5D-5L VAS records the respondent's self-rated health on a 20 cm vertical, visual analogue scale. It is rated by the respondent on a scale 0 to 100, with 0 being "the worst health you can imagine" and 100 being "the best health you can imagine". TTD in EQ-5D-5L VAS is defined as the time from baseline to the first onset of a 7 point or greater decrease from baseline in EQ-5D-5L VAS, with or without subsequent confirmation, under a right-censoring rule.
Measured: Time of last PRO assessment (up to ~2 years)
CRR by BICR (Cohort B)
CRR is defined as the percentage of participants with CIS achieving a CR.
Measured: Up to ~3.5 years
24-Month EFS Rate (Cohort B)
EFS is defined as the time from randomization until UC-defined event, or death due to any cause. The 24-month EFS rate is defined as the percentage of participants with EFS at 24 months.
Measured: 24 months after EFS (Up to ~5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2018
- Study start24 Dec 2018
- Primary completion31 Jul 2028 (estimated)
- Study completion20 Nov 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for High-risk Non-muscle Invasive Bladder CancerStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- None (open label)
- Enrolment
- 1,397 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03711032
- Sponsor's protocol ID
- 3475-676
- Other IDs
- MK-3475-676, 194713, jRCT2031200390, 2022-501817-29-00, U1111-1282-1555, 2018-001967-22, 2018
- Status last verified
- Oct 2026
- First submitted
- 15 Oct 2018
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
Kamat AM, Shore N, Hahn N, Alanee S, Nishiyama H, Shariat S, Nam K, Kapadia E, Frenkl T, Steinberg G. KEYNOTE-676: Phase III study of BCG and pembrolizumab for persistent/recurrent high-risk NMIBC. Future Oncol. 2020 Apr;16(10):507-516. doi: 10.2217/fon-2019-0817. Epub 2020 Mar 12.
PubMed 32162533