Study of Nivolumab in Combination With Ipilimumab or Standard of Care Chemotherapy Compared to the Standard of Care Chemotherapy Alone in Treatment of Participants With Untreated Inoperable or Metastatic Urothelial Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine whether an investigational immunotherapy nivolumab in combination with ipilimumab or in combination with standard of care chemotherapy is more effective than standard of care chemotherapy alone in treating participants with previously untreated inoperable or metastatic urothelial cancer.

Official Title
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A Phase 3, Open-label, Randomized Study of Nivolumab Combined With Ipilimumab, or With Standard of Care Chemotherapy, Versus Standard of Care Chemotherapy in Participants With Previously Untreated Unresectable or Metastatic Urothelial Cancer

Conditions
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Urothelial Cancer

Intervention / Treatment
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* Biological: Nivolumab
* Biological: Ipilimumab
* Drug: Gemcitabine
* Drug: Cisplatin
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytological evidence of metastatic or surgically inoperable transitional cell cancer (TCC) of the urothelium involving the renal pelvis, ureter, bladder or urethra No prior systemic chemotherapy for metastatic or surgically inoperable urothelial cancer (UC) Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 Women and men must agree to follow specific methods of contraception, if applicable Exclusion Criteria: Disease that is suitable for local therapy administered with curative intent Any serious or uncontrolled medical disorder in the opinion of the investigator that may increase the risk associated with study participation or study drug administration or interfere with the interpretation of study results Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways 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: Arm A: Investigational immunotherapy<br> | Biological: Nivolumab<br>* Specified Dose on Specified Days<br>* Other names: Opdivo;Biological: Ipilimumab<br>* Specified Dose on Specified Days<br>* Other names: Yervoy;|
| Active Comparator: Arm B: Standard of care chemotherapy<br> | Drug: Gemcitabine<br>* Specified Dose on Specified Days<br>Drug: Cisplatin<br>* Specified Dose on Specified Days<br>Drug: Carboplatin<br>* Specified Dose on Specified Days<br>|
| Experimental: Arm C: Investigational immunotherapy<br> | Biological: Nivolumab<br>* Specified Dose on Specified Days<br>* Other names: Opdivo;Drug: Gemcitabine<br>* Specified Dose on Specified Days<br>Drug: Cisplatin<br>* Specified Dose on Specified Days<br>|
| Active Comparator: Arm D: Standard of care chemotherapy<br> | Drug: Gemcitabine<br>* Specified Dose on Specified Days<br>Drug: Cisplatin<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 |
| --- | --- | --- |
| Overall survival (OS) in cisplatin-ineligible randomized participants |  | Up to 55 months | 
| Overall survival (OS) in PD-L1 positive (>=1%) randomized participants by immunohistochemistry (IHC) |  | Up to 52 months | 
| Progression-free survival (PFS) by blinded independent central review (BICR) (using RECIST 1.1) in cisplatin-eligible participants with previously untreated, unresectable or metastatic UC |  | Up to 64 months | 
| Overall survival (OS) in cisplatin-eligible participants with previously untreated, unresectable or metastatic UC |  | Up to 64 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) in all randomized participants |  | Up to 55 months | 
| Progression-free survival (PFS) by blinded independent central review (BICR) (using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1) in cisplatin-ineligible randomized participants |  | Up to 55 months | 
| Progression-free survival (PFS) by blinded independent central review (BICR) (using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1) in PD-L1 positive (≥1%) randomized participants |  | Up to 55 months | 
| Progression-free survival (PFS) by blinded independent central review (BICR) (using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1) in all randomized participants |  | Up to 55 months | 
| European Organisation for Research and Treatment of Care (EORTC) QLQ-C30 Global Health Status score in all randomized participants |  | Up to 55 months | 
| European Organisation for Research and Treatment of Care (EORTC) QLQ-C30 Global Health Status score in cisplatin eligible participants with previously untreated, unresectable or metastatic UC |  | Up to 64 months | 
| Progression-free survival (PFS) by BICR by PD-L1 expression at >=1% by immunohistochemistry (IHC) |  | Up to 64 months | 
| Overall survival (OS) by PD-L1 expression at ≥ 1% expression by immunohistochemistry (IHC) |  | Up to 64 months |