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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Urinary Bladder Neoplasms

Intervention / Treatment
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* Biological: Nivolumab
* Biological: BCG
* Drug: BMS-986205


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab monotherapy<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|
| Experimental: Nivolumab + BCG<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;Biological: BCG<br>* Specified dose on specified days<br>* Other names: Bacillus Calumette-Guerin;|
| Experimental: Nivolumab + BMS-986205<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;Drug: BMS-986205<br>* Specified dose on specified days<br>|
| Experimental: Nivolumab + BMS-986205 + BCG<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;Biological: BCG<br>* Specified dose on specified days<br>* Other names: Bacillus Calumette-Guerin;Drug: BMS-986205<br>* Specified dose on specified days<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bladder Cancer, BCG-unresponsive, Nivolumab, Intravesical BCG, NMIBC, Non-Muscle Invasive, BMS-986205, CheckMate 9UT