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
Overview
- Phase
- Phase 3
- Intervention
- Nivolumab
- Conditions
- Urothelial Cancer
- Sponsor
- Bristol-Myers Squibb
- Enrollment
- 1314
- Locations
- 296
- Primary Endpoint
- Overall Survival (OS) in Cisplatin-ineligible Randomized Participants for Primary Study
- Status
- Active, not recruiting
- Last Updated
- last month
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Arm A: Investigational immunotherapy
Intervention: Nivolumab
Arm A: Investigational immunotherapy
Intervention: Ipilimumab
Arm B: Standard of care chemotherapy
Intervention: Gemcitabine
Arm B: Standard of care chemotherapy
Intervention: Cisplatin
Arm B: Standard of care chemotherapy
Intervention: Carboplatin
Arm C: Investigational immunotherapy
Intervention: Nivolumab
Arm C: Investigational immunotherapy
Intervention: Gemcitabine
Arm C: Investigational immunotherapy
Intervention: Cisplatin
Arm D: Standard of care chemotherapy
Intervention: Gemcitabine
Arm D: Standard of care chemotherapy
Intervention: Cisplatin
Outcomes
Primary Outcomes
Overall Survival (OS) in Cisplatin-ineligible Randomized Participants for Primary Study
Time Frame: From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months)
This measure looks at how long participants who cannot receive cisplatin (a type of chemotherapy) live after being placed into a treatment group in the primary study. Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization. This helps to understand if the treatment can help people who are unable to receive cisplatin chemotherapy live longer.
Overall Survival (OS) in Programmed Death-Ligand 1 (PD-L1) Positive (≥ 1%) Randomized Participants by Immunohistochemistry (IHC) for Primary Study
Time Frame: From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months)
This measure looks at how long participants with PD-L1 positive tumors (meaning their tumor cells have at least 1% PD-L1, as determined by a laboratory test called immunohistochemistry or IHC) live after being placed into a treatment group in the primary study. Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization. This helps to understand whether the treatment can help people with PD-L1 positive tumors live longer.
Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in Cisplatin-eligible Participants for Sub-study
Time Frame: From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months)
This measure looks at how long people who can receive cisplatin chemotherapy live without their cancer getting worse after being assigned to a treatment group in the sub-study. Progression-Free Survival (PFS) is the time from when a participant is assigned to a group (randomization) until their cancer is first shown to get worse (progress), based on reviews by independent experts who do not know which treatment was given. These experts use standard rules (RECIST 1.1) to decide if the cancer has progressed. If a participant dies before their cancer is shown to get worse, the date of death will be used as the time their disease progressed. If a participant's cancer does not get worse and they do not die during the study, their PFS will be measured up to the date of their last tumor check. This helps to understand if the treatment helps people eligible for cisplatin live longer without their cancer progressing.
Overall Survival (OS) in Cisplatin-eligible Participants for Sub-study
Time Frame: From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months)
This measure looks at how long people who are able to receive cisplatin (a type of chemotherapy) live after being placed into a treatment group in the sub-study. Overall Survival (OS) is defined as the time between the date a participant is randomized (assigned to a treatment group) and the date of death from any cause. For participants without documentation of death, OS will be measured up to the last date the participant was known to be alive. If a participant was randomized but had no follow-up information, OS will be counted from the date of randomization. This helps to understand if the treatment can help people who are eligible for cisplatin chemotherapy live longer.
Secondary Outcomes
- Overall Survival (OS) in All Randomized Participants for Primary Study(From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 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 for Primary Study(From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months))
- Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] in Programmed Death-Ligand 1 (PD-L1) Positive (≥ 1%) Participants for Primary Study(From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 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 for Primary Study(From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months))
- Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score in All Randomized Participants for Primary Study(At Baseline, Week 4, Week 10, Week 16, Week 20, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, Week 108, Week 120, Week 144, Week 156, Week 168, Week 180 and Week 192)
- Change From Baseline in the European Organization for Research and Treatment of Care Quality-of-Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for Sub-study(At Baseline, Week 4, Week 10, Week 16, Week 20, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96, Week 108, and Week 120)
- Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] by Programmed Death-Ligand 1 (PD-L1) Expression at ≥1% Expression by Immunohistochemistry (IHC) for Sub-study(From the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first (up to approximately 89 months))
- Overall Survival (OS) by Blinded Independent Central Review (BICR) [Using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1] by Programmed Death-Ligand 1 (PD-L1) Expression at ≥1% Expression by Immunohistochemistry (IHC) for Sub-study(From the date of randomization to the date of death from any cause, or data cut-off date, whichever occurred first (up to approximately 89 months))