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)
High-risk Non-muscle Invasive Bladder Cancer
About this trial
This is an interventional treatment trial for High-risk Non-muscle Invasive Bladder Cancer focused on measuring 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)
Eligibility Criteria
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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
- 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
Sites / Locations
- Alaska Urological Institute dba Alaska Clinical Research Center ( Site 1083)
- Mayo Clinic in Arizona - Phoenix ( Site 1094)Recruiting
- Arizona Urology Specialists (AUS)-Professional Park ( Site 1096)Recruiting
- UCLA Hematology/Oncology - Westwood (Building 200 Suite 140)-Department of Urology/Institute of Uro
- University of California Irvine Medical Center ( Site 1061)Recruiting
- Genesis Research LLC ( Site 1065)Recruiting
- Colorado Clinical Research ( Site 1100)Recruiting
- Urological Research Network ( Site 1106)Recruiting
- Mayo Clinic in Florida-Urology ( Site 1097)Recruiting
- University of Miami Hospital and Clinics, Sylvester Cancer Center ( Site 1056)Recruiting
- Woodlands Medical Specialists, PA ( Site 8002)
- Emory School of Medicine ( Site 1076)Recruiting
- Advanced Urology ( Site 1092)Recruiting
- Northwestern Memorial Hospital ( Site 1101)Recruiting
- Wichita Urology Group ( Site 1086)Recruiting
- Ochsner LSU Health Shreveport - Regional Urology ( Site 1099)Recruiting
- Henry Ford Health System ( Site 1062)Recruiting
- Michigan Institute of Urology ( Site 1077)Recruiting
- Coastal Urology Associates ( Site 1055)
- Morristown Medical Center ( Site 1090)Recruiting
- Rutgers Cancer Institute of New Jersey ( Site 1059)
- St. Peter's Hospital Cancer Care Center ( Site 1087)
- Monter Cancer Center ( Site 1080)Recruiting
- Veterans Affairs New York Harbor Healthcare System-PCF COE ( Site 1112)Recruiting
- Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 1074)Recruiting
- Associated Medical Professionals of NY ( Site 1078)
- TriState Urologic Services PSC Inc. dba The Urology Group ( Site 1091)Recruiting
- University Hospitals Cleveland Medical Center ( Site 1066)
- Ohio State University Arthur G James Cancer Hospital & Richard J Solove Research Institute ( Site 10Recruiting
- OHSU Knight Cancer Institute ( Site 1075)
- Oregon Urology Institute ( Site 1098)Recruiting
- MidLantic Urology ( Site 1071)Recruiting
- Lancaster Urology ( Site 1079)Recruiting
- University of Pennsylvania ( Site 1088)Recruiting
- Carolina Urologic Research Center ( Site 1085)Recruiting
- Urology Associates [Nashville, TN] ( Site 1072)Recruiting
- Urology Clinics of North Texas, PLLC ( Site 1064)Recruiting
- University Of Texas Southwestern Medical Center ( Site 1053)Recruiting
- Texas Oncology-Fort Worth Cancer Center ( Site 8003)
- Houston Metro Urology ( Site 1111)Recruiting
- Texas Oncology-Plano West ( Site 8001)
- Urology San Antonio Research ( Site 1108)Recruiting
- University of Vermont Medical Center ( Site 1057)Recruiting
- Urology of Virginia ( Site 1070)Recruiting
- GenesisCare North Shore ( Site 0010)Recruiting
- Nothern Cancer Institute ( Site 0003)
- Sydney Adventist Hospital ( Site 0001)
- Epworth Hospital ( Site 0009)Recruiting
- Ordensklinikum Linz GmbH Elisabethinen ( Site 0052)Recruiting
- Univ. Klinik f. Urologie Innsbruck ( Site 0051)
- Medizinische Universität Wien ( Site 0054)Recruiting
- Universitaetsklinik Salzburg ( Site 0053)Recruiting
- UZA University Hospital Antwerp ( Site 0105)Recruiting
- CHU UCL Namur Site de Godinne ( Site 0103)Recruiting
- O.L.V. Ziekenhuis Aalst ( Site 0106)Recruiting
- AZ Maria Middelares Gent ( Site 0102)Recruiting
- UZ Gent ( Site 0101)Recruiting
- Hospital São Carlos-Oncocentro Ce ( Site 1558)
- Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 1551)Recruiting
- Fundação Pio XII - Hospital de Câncer de Barretos-Unidade de Pesquisa Clínica ( Site 1553)
- ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO ( Site 1560)
- Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 1554)
- BP - A Beneficencia Portuguesa de São Paulo ( Site 1559)
- Exdeo Clinical Research Inc. ( Site 0165)
- Silverado Resarch Inc. ( Site 0155)
- Horizon Health Network ( Site 0160)Recruiting
- Princess Margaret Cancer Centre ( Site 0153)Recruiting
- CIUSSS du Saguenay-Lac-St-Jean ( Site 0164)Recruiting
- CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0157)Recruiting
- CHUS - Hopital Fleurimont ( Site 0152)Recruiting
- Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0Recruiting
- Cancer Hospital Chinese Academy of Medical Science-Urinary Surgery ( Site 1766)Recruiting
- Peking University First Hospital ( Site 1759)Recruiting
- Beijing Cancer hospital-Urinary Surgery ( Site 1755)Recruiting
- The First Affiliated hospital of Xiamen University-Urology ( Site 1776)Recruiting
- SUN YAT-SEN UNIVERSITY CANCER CENTRE ( Site 1752)Recruiting
- Sun Yat-sen Memorial Hospital, Sun Yat-sen University-Urology Surgery ( Site 1751)Recruiting
- The First Affiliated Hospital of Guangzhou Medical University-Urology ( Site 1777)Recruiting
- ShenZhen People's Hospital ( Site 1778)Recruiting
- Harbin Medical University Cancer Hospital-urology ( Site 1772)Recruiting
- Henan Cancer Hospital-Urology ( Site 1770)Recruiting
- Wuhan Union Hospital ( Site 1771)Recruiting
- Tongji Hospital Tongji Medical,Science & Technology ( Site 1768)Recruiting
- Hunan Cancer Hospital ( Site 1763)Recruiting
- Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School-Urology ( SRecruiting
- The Second Affiliated Hospital of Soochow University-Urology ( Site 1773)Recruiting
- The First Affiliated Hospital of Xi'an Jiaotong University ( Site 1764)Recruiting
- West China Hospital Sichuan University ( Site 1767)Recruiting
- The Second Hospital of Tianjin Medical University ( Site 1769)Recruiting
- Zhejiang Provincial People's Hospital-Urology ( Site 1762)Recruiting
- The First Affiliated Hospital of Wenzhou Medical University-Urology Surgery ( Site 1774)Recruiting
- Instituto de Cancerología-Oncology ( Site 1609)
- Fundación Hospital San Vicente de Paúl - Rionegro - Centros Especializados o de Centros Especializad
- Oncomedica S.A.-Oncomedica S.A ( Site 1604)
- Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 1605)
- Administradora Country S.A. - Clinica del Country ( Site 1607)
- Oncologos del Occidente ( Site 1608)
- Hemato Oncologos SA-Oncology ( Site 1601)
- Clínica Imbanaco S.A.S ( Site 1611)
- CIMCA ( Site 1550)Recruiting
- Policlinico San Bosco ( Site 0600)Recruiting
- Tampere University Hospital [Tampere Finland] ( Site 0201)
- Centre Hospitalier Universitaire Dijon Bourgogne - Hôpital François Mitterrand-Urology ( Site 1355)Recruiting
- Hôpital Foch-Urology department ( Site 1351)Recruiting
- Centre Hospitalier Universitaire de Rennes - Hôpital Pontchaillou ( Site 1353)Recruiting
- Hopital Claude Huriez - CHU de Lille ( Site 1360)Recruiting
- HENRI MONDOR HOSPITAL ( Site 1357)Recruiting
- Klinikum Rechts der Isar. Technischen Universitaet Muenchen ( Site 0266)Recruiting
- Klinikum Weiden ( Site 0259)Recruiting
- Universitaetsklinikum Wuerzburg ( Site 0265)Recruiting
- Krankenhaus der Barmherzigen Brüder Trier-Abteilung für Urologie und Kinderurologie ( Site 0262)Recruiting
- Universitaetsklinikum Jena ( Site 0252)Recruiting
- Olympion General Clinic ( Site 0306)Recruiting
- General University Hospital of Patras ( Site 0302)
- ATTIKON GENERAL UNIVERSITY HOSPITAL ( Site 0304)Recruiting
- Antikarkiniko Nosokomeio Thessalonikis THEAGENIO ( Site 0303)
- University Hospital of Larissa ( Site 0301)Recruiting
- Onco Go, S.A ( Site 1454)
- INTEGRA Cancer Institute ( Site 1451)
- Grupo Medico Angeles-Grupo Medico Angeles ( Site 1453)
- Pécsi Tudományegyetem Klinikai Központ-Urológiai Klinika ( Site 1304)Recruiting
- Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ-Urológiai Klinika ( Site 1303)Recruiting
- Semmelweis University-Urológiai Klinika ( Site 1301)Recruiting
- Debreceni Egyetem Klinikai Kozpont ( Site 1302)Recruiting
- Ospedale Clinicizzato Santissima Annunziata ( Site 0361)Recruiting
- Ospedale San Raffaele ( Site 0362)Recruiting
- Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0353)Recruiting
- Ospedale Mauriziano-SCDU ONCOLOGIA MEDICA ( Site 0366)Recruiting
- Azienda Ospedaliero Universitaria Careggi ( Site 0360)Recruiting
- Osp Generale Reg di Bolzano ( Site 0355)
- Azienda USL 8 di Arezzo-Medical Oncology ( Site 0363)Recruiting
- Istituto Tumori Giovanni Paolo II ( Site 0357)
- Ospedale San Martino ( Site 0351)
- Ospedale Buccheri La Ferla Fatebenefratelli ( Site 0352)Recruiting
- Policlinico Universitario A. Gemelli ( Site 0358)Recruiting
- A.O.U. di Verona - Ospedale Civile Maggiore Borgo Trento ( Site 0356)
- Hirosaki University Hospital ( Site 0407)Recruiting
- Ehime University Hospital ( Site 0414)Recruiting
- University of Tsukuba Hospital ( Site 0412)Recruiting
- St. Marianna University Hospital ( Site 0415)Recruiting
- Kitasato University Hospital ( Site 0403)Recruiting
- Yokosuka Kyosai Hospital ( Site 0406)Recruiting
- Nara Medical University Hospital ( Site 0411)Recruiting
- Hamamatsu University Hospital ( Site 0416)Recruiting
- Chiba Cancer Center ( Site 0401)Recruiting
- Harasanshin Hospital ( Site 0410)Recruiting
- Osaka International Cancer Institute ( Site 0413)Recruiting
- Osaka Metropolitan University Hospital ( Site 0404)Recruiting
- Tokyo Medical and Dental University Hospital ( Site 0409)Recruiting
- Keio University Hospital ( Site 0405)Recruiting
- Asan Medical Center ( Site 0804)
- Korea University Anam Hospital ( Site 0801)Recruiting
- Seoul National University Hospital ( Site 0802)Recruiting
- Samsung Medical Center ( Site 0803)
- University Malaya Medical Centre ( Site 1180)
- Maastricht University Medical Centre ( Site 0453)Recruiting
- Erasmus MC ( Site 0451)Recruiting
- Universitair Medisch Centrum Utrecht-Medical Oncology ( Site 0455)
- Akershus University Hospital ( Site 0553)Recruiting
- Stavanger universitetssykehus ( Site 0555)Recruiting
- Hospital Nacional Guillermo Almenara Irigoyen ( Site 0601)
- Oncosalud ( Site 0603)Recruiting
- Hospital Militar Central [Lima, Peru] ( Site 0604)Recruiting
- Uniwesytecki Szpital Kliniczny we Wroclawiu ( Site 0669)Recruiting
- Nasz Lekarz Przychodnie Medyczne ( Site 0679)Recruiting
- Pratia MCM Krakow ( Site 0668)
- Szpital Wojewódzki im. Świętego Lukasza SP ZOZ w Tarnowie ( Site 0681)Recruiting
- Urologica Praktyka Lekarska Adam Marcheluk ( Site 0654)
- Medical Concierge Centrum Medyczne ( Site 0676)Recruiting
- Luxmed Onkologia sp. z o. o. ( Site 0653)
- Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 0678)Recruiting
- Szpital Specjalistyczny w Koscierzynie Sp. z o.o. ( Site 0671)
- Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku ( Site 0655)Recruiting
- LIFTMED ( Site 0652)
- Clinical Research Center Sp. z o.o. ( Site 0674)Recruiting
- 2CA Braga. Centro Clinico Academico ( Site 0705)Recruiting
- Inst. Portugues de Oncologia de Coimbra Francisco Gentil EPE ( Site 0704)
- Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE ( Site 0708)
- CHLN Hospital Santa Maria ( Site 0702)Recruiting
- Hospital CUF Descobertas ( Site 0706)
- Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 0701)Recruiting
- Advance Urology and Laparoscopic Center ( Site 0757)
- Ad-Vance Medical Research ( Site 0756)
- Hospital Universitario Lucus Augusti ( Site 0852)Recruiting
- Hospital Universitario Quiron Madrid ( Site 0862)Recruiting
- Clinica Universitaria de Navarra ( Site 0863)
- Fundacio Puigvert ( Site 0864)Recruiting
- Hospital Universitario Gregorio Maranon ( Site 0854)Recruiting
- Clinica Universitaria Navarra - Madrid ( Site 0860)
- MD Anderson Cancer Center Madrid ( Site 0859)Recruiting
- Hospital Universitario Ramon y Cajal ( Site 0857)Recruiting
- Hospital Universitario La Paz ( Site 0866)Recruiting
- Hospital La Fe de Valencia ( Site 0855)Recruiting
- Universitaetsspital Basel ( Site 1201)Recruiting
- Hopitaux Universitaires de Geneve HUG ( Site 1204)Recruiting
- Universitaetsspital Zurich ( Site 1203)Recruiting
- China Medical University Hospital-Department of Urology ( Site 1654)
- Taichung Veterans General Hospital ( Site 1653)
- Taipei Veterans General Hospital ( Site 1652)
- Ankara Universitesi Tip Fakultesi Hastanesi ( Site 0966)Recruiting
- Eskisehir Osmangazi Universitesi Hastanesi ( Site 0953)Recruiting
- Memorial Sisli Hastanesi-Medical Oncology ( Site 0965)Recruiting
- TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 0963)Recruiting
- Dokuz Eylul Universitesi ( Site 0959)
- Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 0961)Recruiting
- Raigmore Hospital ( Site 1006)Recruiting
- St Bartholomew s Hospital ( Site 1008)Recruiting
- St Georges University Hospitals NHS Foundation Trust. ( Site 1005)Recruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Experimental
BCG plus Pembrolizumab: Post-induction Cohort A (Arm A-1)
BCG Monotherapy: Post-induction Cohort A (Arm A-2)
BCG plus Pembrolizumab: BCG Naïve Cohort B-Reduced Maintenance (Arm B-1)
BCG plus Pembrolizumab: BCG Naïve Cohort B-Full Maintenance (Arm B-2)
BCG Monotherapy: BCG Naïve Cohort B (Arm B-3)
Participants receive BCG (Induction and Maintenance) in combination with 200 mg pembrolizumab administered intravenously (IV) every 3 weeks (Q3W) for 35 doses (~2 years).
Participants receive BCG monotherapy (Induction and Maintenance).
Participants receive BCG (Induction and reduced Maintenance) in combination with 400 mg pembrolizumab administered IV every 6 weeks (Q6W) for 9 doses (~1 year).
Participants receive BCG (Induction and full Maintenance) in combination with 400 mg pembrolizumab administered IV Q6W for 9 doses (~1 year).
Participants receive BCG monotherapy (Induction and Maintenance).