A Study of Nivolumab or Nivolumab Plus Experimental Medication BMS-986205 With or Without Bacillus Calumette-Guerin (BCG) in BCG Unresponsive Bladder Cancer That Has Not Invaded Into the Muscle Wall of the Bladder (CheckMate 9UT)

A Phase 2, Randomized, Open-label Study of Nivolumab or Nivolumab/BMS-986205 Alone or Combined With Intravesical BCG in Participants With BCG-Unresponsive, High-Risk, Non-Muscle Invasive Bladder Cancer

A study to evaluate the safety and tolerability of nivolumab or nivolumab Plus BMS-986205 with or without BCG in BCG-Unresponsive non-muscle invasive Bladder Cancer.

Study Overview

• Status: Terminated
• Conditions: Urinary Bladder Neoplasms
• Intervention / Treatment: Biological: Nivolumab; Biological: BCG; Drug: BMS-986205

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina, 5000
    • Instituto Oncologico de Cordoba
  • Mendoza, Argentina, 5500
    • Local Institution - 0137
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, 1426
      • Local Institution - 0068
  • Distrito Federal
    • Capital Federal, Distrito Federal, Argentina, C1280AEB
      • Local Institution - 0065
    • Ciudad Autonoma Buenos Aires, Distrito Federal, Argentina, 1118
      • Local Institution - 0089
  • RIO Negro
    • Viedma, RIO Negro, Argentina, 8500
      • Local Institution
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Local Institution - 0146
    • St Leonards, New South Wales, Australia, 2065
      • Local Institution - 0148
• Brazil
  • Rio de Janeiro, Brazil, 20230-130
    • Local Institution - 0150
  • Sao Paulo, Brazil, 01246-000
    • Local Institution - 0074
  • Ceara
    • Fortaleza, Ceara, Brazil, 60135-237
      • Local Institution - 0072
  • Parana
    • Curitiba, Parana, Brazil, 80810050
      • Local Institution - 0151
  • RIO Grande DO SUL
    • Porto Alegre, RIO Grande DO SUL, Brazil, 91350-200
      • Local Institution - 0073
  • Santa Catarina
    • Itacorubi, Florianopolis, Santa Catarina, Brazil, 88034
      • Local Institution
  • Sao Paulo
    • Jau, Sao Paulo, Brazil, 17210-120
      • Local Institution - 0078
• Canada
  • Ontario
    • North York, Ontario, Canada, M2K 1E1
      • Local Institution - 0143
    • Toronto, Ontario, Canada, M4N 3M5
      • Local Institution - 0086
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 0084
  • Quebec
    • Quebec City, Quebec, Canada, G1J 1Z4
      • Local Institution - 0046
• Chile
  • Metropolitana
    • Santiago, Metropolitana, Chile, 8420383
      • Local Institution - 0154
    • Santiago, Metropolitana, Chile
      • Local Institution - 0069
• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Local Institution - 0116
    • Beijing, Beijing, China, 100021
      • Local Institution - 0128
    • Beijing, Beijing, China, 100034
      • Local Institution - 0131
    • Beijing, Beijing, China, 100191
      • Local Institution - 0099
  • Chongqing
    • Chongqing, Chongqing, China, 400030
      • Local Institution - 0129
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Local Institution - 0108
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Local Institution - 0117
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Local Institution - 0102
  • Jiangxi
    • Nan Chang, Jiangxi, China, 330000
      • Local Institution - 0109
  • Shandong
    • Jinan, Shandong, China, 250012
      • Local Institution - 0112
    • Yantai, Shandong, China, 264000
      • Local Institution - 0111
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Local Institution - 0094
    • Shanghai, Shanghai, China, 200025
      • Local Institution - 0098
    • Shanghai, Shanghai, China, 200040
      • Local Institution - 0097
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Local Institution - 0120
  • Tianjin
    • Tianjin, Tianjin, China, 300211
      • Local Institution - 0133
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Local Institution - 0126
• France
  • Bordeaux Cedex, France, 33076
    • Local Institution - 0031
  • Lille, France, 59037
    • Local Institution - 0088
  • Strasbourg, France, 67200
    • Local Institution - 0091
  • Hauts-de-Seine
    • Suresnes, Hauts-de-Seine, France, 92151
      • Local Institution - 0027
  • Maine-et-Loire
    • Angers, Maine-et-Loire, France, 49933
      • Local Institution - 0028
• Hong Kong
  • Hong Kong, Hong Kong
    • Local Institution - 0093
• Italy
  • Milano, Italy, 20133
    • IRCCS Istituto Nazionale Tumori Milano
  • Napoli, Italy, 80131
    • Instituto Nazionale Tumori Fondazione G. Pascale
  • Pisa, Italy, 56126
    • Azienda Ospedaliera Universitaria Pisana
• Mexico
  • Chiapas
    • Tuxtla Gutierrez, Chiapas, Mexico, 290838
      • Local Institution - 0062
  • Distrito Federal
    • Ciudad de Mexico, Distrito Federal, Mexico, 06100
      • Local Institution - 0055
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Local Institution - 0004
  • Nijmegen, Netherlands, 6525GA
    • Local Institution - 0003
  • Utrecht, Netherlands, 3584CX
    • Local Institution - 0005
• Russian Federation
  • Omsk, Russian Federation, 644013
    • Local Institution - 0070
  • Saint-Petersburg, Russian Federation, 194044
    • Local Institution - 0054
  • Saint-Petersburg, Russian Federation, 199034
    • Local Institution - 0153
• Spain
  • Madrid, Spain, 28041
    • Local Institution
  • Malaga, Spain, 29010
    • Local Institution - 0033
  • Santander, Spain, 39008
    • Local Institution - 0139
  • Valencia, Spain, 46010
    • Local Institution - 0136
• United Kingdom
  • Lancaster, United Kingdom, LA1 4RP
    • Local Institution - 0015
  • Essex
    • Chelmsford, Essex, United Kingdom, CM1 7ET
      • Local Institution
  • Greater London
    • London, Greater London, United Kingdom, N18 1QX
      • Local Institution
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Local Institution - 0013
• United States
  • California
    • Los Angeles, California, United States, 90033
      • Local Institution - 0044
    • Riverside, California, United States, 92505
      • Local Institution - 0081
    • San Francisco, California, United States, 94158
      • Local Institution - 0087
  • Florida
    • Tampa, Florida, United States, 33612
      • Local Institution - 0125
  • Georgia
    • Hapeville, Georgia, United States, 30354
      • Local Institution - 0056
  • Illinois
    • New Lenox, Illinois, United States, 60451
      • Local Institution - 0023
  • Kansas
    • Wichita, Kansas, United States, 67226
      • Wichita Urology Group
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Local Institution - 0001
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Local Institution - 0077
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Local Institution - 0032
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Local Institution - 0040
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Local Institution - 0144
    • Voorhees, New Jersey, United States, 08043
      • Deleware Valley Urology, LLC
  • New York
    • New York, New York, United States, 10016
      • Local Institution - 0051
  • Ohio
    • Columbus, Ohio, United States, 43212
      • Local Institution - 0058
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • Local Institution - 0036
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Local Institution - 0049
    • Myrtle Beach, South Carolina, United States, 29572
      • Local Institution - 0002
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Local Institution - 0057
  • Texas
    • Dallas, Texas, United States, 75231
      • Urology Clinics Of North Texas, Pa
    • Houston, Texas, United States, 77030
      • Local Institution - 0048
    • Houston, Texas, United States, 77030
      • Local Institution - 0140
    • Lubbock, Texas, United States, 79415
      • Local Institution - 0047
    • San Antonio, Texas, United States, 78229
      • Urology San Antonio Research, PA
  • Washington
    • Seattle, Washington, United States, 98195
      • Local Institution - 0141

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pathologically demonstrated BCG-unresponsive, carcinoma in situ (CIS)-containing high-risk non-muscle-invasive bladder cancer (NMIBC) defined as CIS with or without papillary component
• Participants must have CIS to be eligible.
• Predominant histologic component (> 50%) must be urothelial (transitional cell) carcinoma
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

Exclusion Criteria:

• Sign of locally advanced disease or metastatic bladder cancer
• Urothelial cancer (UC) in the upper genitourinary tract (kidneys, renal collecting systems, ureters) within 24 months of enrollment
• Prior immuno-oncology therapy

Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab monotherapy	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo
Experimental: Nivolumab + BCG	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo; Biological: BCG; Specified dose on specified days; Other Names: Bacillus Calumette-Guerin
Experimental: Nivolumab + BMS-986205	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo; Drug: BMS-986205; Specified dose on specified days
Experimental: Nivolumab + BMS-986205 + BCG	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo; Biological: BCG; Specified dose on specified days; Other Names: Bacillus Calumette-Guerin; Drug: BMS-986205; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. AEs are reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.	From first dose to 30 days post last dose of study treatment (an average of 45 weeks up to approximately 64 weeks)
Number of Participants With Serious Adverse Events (SAEs)	Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: Results in death; Is life-threatening (an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe); Requires inpatient hospitalization or causes prolongation of existing hospitalization. SAEs are reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.	From first dose to 30 days post last dose of study treatment (an average of 45 weeks up to approximately 64 weeks)
Number of Participants With Adverse Events (AEs) Leading to Discontinuation of Study Treatment	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. AEs leading to discontinuation are reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.	From first dose to 30 days post last dose of study treatment (an average of 45 weeks up to approximately 64 weeks)
Number of Participants Immune-Mediated Adverse Events (IMAEs)	IMAEs are AEs consistent with an immune-mediated mechanism or immune-mediated component for which non-inflammatory etiologies (eg, infection or tumor progression) have been ruled out. IMAEs can include events with an alternate etiology which were exacerbated by the induction of autoimmunity IMAEs are reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.	From first dose to 30 days post last dose of study treatment (an average of 45 weeks up to approximately 64 weeks)
Number of Participants Who Died	Number of participants who died.	From first dose to 100 days post last dose of study treatment (an average of 45 weeks up to approximately 74 weeks)
Number of Participants With Specific Liver Laboratory Abnormalities	On-treatment laboratory evaluations are evaluations taken after the day (and time, if collected and not missing) of first dose of study treatment. For participants who are off study treatment, evaluations were within a safety window of 30 days after the last dose of study treatment. ALT = Alanine Aminotransferase AST = Aspartate Aminotransferase ULN = Upper Limit of Normal.	From first dose to 30 days post last dose of study treatment (an average of 45 weeks up to approximately 64 weeks)
Number of Participants With Specific Thyroid Laboratory Abnormalities	On-treatment laboratory evaluations are evaluations taken after the day (and time, if collected and not missing) of first dose of study treatment. For participants who are off study treatment, evaluations were within a safety window of 30 days after the last dose of study treatment. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal	From first dose to 30 days post last dose of study treatment (an average of 45 weeks up to approximately 64 weeks)
Number of Participants With Changes From Baseline Laboratory Values	On-study laboratory parameters include hematology, chemistry, liver function, and renal function. On-study laboratory evaluations are evaluations taken after the day (and time, if collected and not missing) of first dose of study treatment. For participants who are off study treatment, evaluations were within a safety window of 30 days after the last dose of study treatment. On-study lab parameters are reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.	From baseline to 30 days post last dose of study treatment (an average of 45 weeks up to approximately 64 weeks)
Number of Participants With Adverse Events (AEs) by Anti-Drug- Antibody (ADA) Status	An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. An Anti-drug antibody (ADA) is defined as biologic drug-reactive antibody, including pre-existing host antibodies that are cross-reactive with the administered biologic drug. An ADA-positive participant has at least one ADA positive-sample relative to baseline at any time after initiation of treatment An ADA-negative participant doesn't not have an ADA-positive sample after the initiation of treatment.	From first dose to 30 days post last dose of study treatment (an average of 45 weeks up to approximately 64 weeks)
Number of Participants With Serious Adverse Events (SAEs) by Anti-Drug- Antibody (ADA) Status	Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: Results in death; Is life-threatening (an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe); Requires inpatient hospitalization or causes prolongation of existing hospitalization. An Anti-drug antibody (ADA) is defined as biologic drug-reactive antibody, including pre-existing host antibodies that are cross-reactive with the administered biologic drug. An ADA-positive participant has at least one ADA positive-sample relative to baseline at any time after initiation of treatment An ADA-negative participant doesn't not have an ADA-positive sample after the initiation of treatment.	From first dose to 30 days post last dose of study treatment (an average of 45 weeks up to approximately 64 weeks)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2018
• Primary Completion (Actual): August 22, 2022
• Study Completion (Actual): August 24, 2022

Study Registration Dates

• First Submitted: April 17, 2018
• First Submitted That Met QC Criteria: April 26, 2018
• First Posted (Actual): May 8, 2018

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 31, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Nivolumab; NMIBC; Bladder Cancer; BCG-unresponsive; Intravesical BCG; Non-Muscle Invasive; BMS-986205; CheckMate 9UT
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Linrodostat
• Other Study ID Numbers: CA209-9UT; 2017-003581-27 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No