A Study Comparing Nivolumab, Nivolumab in Combination With Ipilimumab and Placebo in Participants With Localized Kidney Cancer Who Underwent Surgery to Remove Part of a Kidney

Study Overview
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Brief Summary
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The purpose of this study is to determine whether nivolmab alone or the combination of nivolumab and ipilimumab versus placebo, is safe and effective for delaying or preventing recurrence of cancer in participants who have experienced partial or entire removal of a kidney.

Detailed Description
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The study has two primary endpoints. The first primary completion date is anticipated to be reached July 2022 (DFS in Part A). The second primary completion date is anticipated to be reached July 2024 (DFS in Part B).

Official Title
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A Phase 3 Randomized, Double-Blind Study of Nivolumab Monotherapy or Nivolumab Combined With Ipilimumab vs Placebo in Participants With Localized Renal Cell Carcinoma Who Underwent Radical or Partial Nephrectomy and Who Are at High Risk of Relapse

Conditions
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Carcinoma, Renal Cell

Intervention / Treatment
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* Biological: nivolumab
* Biological: ipilimumab
* Drug: nivolumab placebo
* Drug: ipilimumab placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kidney tumor has been completely resected with negative surgical margins obtained. The randomization must occur greater than 4 weeks and less than (or equal to) 12 weeks from the date of nephrectomy Pathologic tumor, node, and metastasis (TNM) staging meeting one of the following: pT2a, G3 or G4, N0 M0; pT2b, G any, N0 M0; pT3, (a, b, c), G any, N0 M0; pT4, G any, N0 M0; pT any, G any, N1 M0 Post-nephrectomy tumor shows renal cell cancer (RCC) with a predominantly clear cell histology, including participants with sarcomatoid features Participants must have no clinical or radiological evidence of macroscopic residual disease or distant metastases after nephrectomy Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1 Women must agree to follow methods of contraception, if applicable Exclusion Criteria: Participants with an active known or suspected autoimmune disease Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Any severe or serious, acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation History of allergy or hypersensitivity to study drug components Participants with a condition requiring systemic treatment with corticosteroids Participants who have received a live/attenuated vaccine within 30 days of first treatment 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A, Arm A: nivolumab + ipilimumab<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;|
| Placebo Comparator: Part A, Arm B: nivolumab placebo + ipilimumab placebo<br> | Drug: nivolumab placebo<br>* Specified dose on specified days<br>Drug: ipilimumab placebo<br>* Specified dose on specified days<br>|
| Experimental: Part B, Arm A: nivolumab + ipilimumab<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;|
| Placebo Comparator: Part B, Arm B: nivolumab placebo + ipilimumab placebo<br> | Drug: nivolumab placebo<br>* Specified dose on specified days<br>Drug: ipilimumab placebo<br>* Specified dose on specified days<br>|
| Experimental: Part B, Arm C: nivolumab + ipilimumab placebo<br> | Biological: nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;Drug: ipilimumab placebo<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 |
| --- | --- | --- |
| Disease-free survival (DFS) as assessed by BICR (Part A and Part B) |  | Up to 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) (Part A and Part B) |  | Up to 10 years | 
| Incidence of Adverse Events (AEs) (Part A and Part B) |  | Up to 100 days after the last dose of study treatment | 
| Disease-Free Survival (DFS) as assessed by BICR (Part B: arm A vs. arm C) |  | Up to 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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localized, resected, adjuvant, Renal Cell Carcinoma, Kidney Cancer, Nephrectomy, Clear cell, High Risk of Relapse/Recurrence