An Investigational Immuno-therapy Study of Nivolumab, Compared to Placebo, in Patients With Bladder or Upper Urinary Tract Cancer, Following Surgery to Remove the Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine the effectiveness and safety of Nivolumab compared to placebo in participants who have undergone radical surgery for invasive urothelial cancer.

Official Title
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A Phase 3 Randomized, Double-blind, Multi-center Study of Adjuvant Nivolumab Versus Placebo in Subjects With High Risk Invasive Urothelial Carcinoma (CheckMate 274: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 274)

Conditions
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Various Advanced Cancer

Intervention / Treatment
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* Biological: Nivolumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Must have had invasive urothelial cancer at high risk of recurrence originating in the bladder, ureter, or renal pelvis Must have had radical surgical resection (e.g. radical cystectomy), performed within the last 120 days Must have disease free status as determined by imaging within 4 weeks of dosing Tumor tissue must be provided for biomarker analysis Patients who have not received prior neoadjuvant cisplatin chemotherapy must be ineligible for or refuse cisplatin-based adjuvant chemotherapy Exclusion Criteria: Partial bladder or partial kidney removal (eg, partial cystectomy or partial nephrectomy) Secondary Treatment (eg, adjuvant systemic chemotherapy for bladder cancer) following surgical removal of bladder cancer Subjects with active, known or suspected autoimmune disease Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 day of study drug administration Positive test for hepatitis B virus surface antigen (HBV s Ag) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab<br>Nivolumab dose as specified | Biological: Nivolumab<br> <br> |
| Placebo Comparator: Placebo<br>Placebo dose as specified | Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival (DFS) | The time between the date of randomization and the date of first documented recurrence (local urothelial tract, local non-urothelial tract or distant), or death due to any cause, whichever occurs first. | approximately up to 48 months | 
| Disease Free Survival (DFS) in PD-L1 Expression ≥ 1% Population | The time between the date of randomization and the date of first documented recurrence (local urothelial tract, local non-urothelial tract or distant), or death due to any cause, whichever occurs first. | approximately up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-Urothelial Tract Recurrence Free Survival | The time between the date of randomization and the date of first documented recurrence (local non-urothelial tract or distant), or death due to any cause, whichever occurs first. | up to 53 months | 
| Non-Urothelial Tract Recurrence Free Survival in PD-L1 Expression ≥ 1% Population | The time between the date of randomization and the date of first documented recurrence (local non-urothelial tract or distant), or death due to any cause, whichever occurs first. | up to 53 months | 
| Overall Survival | the time from randomization to the date of death from any cause. | on going | 
| Overall Survival in Participants With PD-L1 Expression ≥ 1% | the time from randomization to the date of death from any cause. | on going | 
| Disease Specific Survival | the time from randomization to the date of death due to disease (urothelial cancer). | on going | 
| Disease Specific Survival in Participants With PD-L1 Expression ≥ 1% | the time from randomization to the date of death due to disease (urothelial cancer). | on going |