A Study of Subcutaneous Nivolumab Versus Intravenous Nivolumab in Participants With Previously Treated Clear Cell Renal Cell Carcinoma That is Advanced or Has Spread

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the drug levels, efficacy, safety, and tolerability of subcutaneous nivolumab versus intravenous nivolumab in participants with previously treated clear cell renal cell carcinoma that is advanced or has spread. The purpose of this study's substudy is to evaluate drug level biocomparability of subcutaneous nivolumab manufactured using two different manufacturing processes.

Official Title
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A Phase 3, Open-label, Randomized, Noninferiority Trial of Subcutaneous Formulation of Nivolumab Versus Intravenous Nivolumab in Participants With Advanced or Metastatic Clear Cell Renal Cell Carcinoma Who Have Received Prior Systemic Therapy

Conditions
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Clear Cell Renal Cell Carcinoma

Intervention / Treatment
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* Biological: Nivolumab and rHuPH20
* Biological: Nivolumab


Participation Criteria
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Eligibility Criteria
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For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Histological confirmation of renal cell carcinoma (RCC) with a clear cell component, including participants who may also have sarcomatoid features Advanced RCC (not amenable to curative surgery or radiation therapy) or metastatic RCC (Stage IV) Measurable disease as defined by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 criteria within 28 days prior to randomization Received no more than 2 prior systemic treatment regimens Intolerance or progression on or after the last treatment regimen received and within 6 months prior to randomization Karnofsky PS ≥ 70 at screening Must agree to follow specific methods of contraception, if applicable Exclusion Criteria: Untreated, symptomatic central nervous system (CNS) metastases Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to randomization Active, known, or suspected autoimmune disease Known human immunodeficiency virus (HIV) positive with an acquired immunodeficiency syndrome (AIDS) defining opportunistic infection within the last year, or a current CD4 count < 350 cells/μL. Participants with HIV are eligible if: They have received established antiretroviral therapy (ART) for at least 4 weeks prior to randomization They continue on ART as clinically indicated while enrolled on study CD4 counts and viral load are monitored per standard of care by a local health care provider Inclusion of participants with HIV should be based on Investigator clinical judgment in consultation with the Medical Monitor NOTE: Testing for HIV must be performed at sites where mandated locally. HIV-positive participants must be excluded where mandated locally Serious or uncontrolled medical disorders including for example, active severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2) infection within approximately 4 weeks prior to screening. In the case of prior SARS-CoV-2 infection, acute symptoms must have resolved based on investigator clinical judgment and, in consultation with Medical Monitor, there are no sequelae that would place the participant at a higher risk of receiving investigational treatment to be eligible Prior treatment with an programmed death receptor-1 (anti-PD-1), programmed death ligand-1 (anti-PD-L1), or cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways Treatment with any live attenuated vaccine within 30 days of first study 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: Arm A<br> | Biological: Nivolumab and rHuPH20<br>* Specified dose on specified days<br>* Other names: BMS-986298;|
| Active Comparator: Arm B<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|
| Experimental: Arm C<br> | Biological: Nivolumab and rHuPH20<br>* Specified dose on specified days<br>* Other names: BMS-986298;|
| Experimental: Arm D<br> | Biological: Nivolumab and rHuPH20<br>* Specified dose on specified days<br>* Other names: BMS-986298;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-averaged serum concentration over 28 days (Cavgd28) |  | Up to 28 days | 
| Trough serum concentration at steady-state (Cminss) |  | Up to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) by Blinded Independent Central Review (BICR) with a minimum of 6 months follow-up |  | Up to 2 years 6 months | 
| Trough serum concentration at day 28 (Cmind28) |  | At 28 days | 
| Maximum serum concentration after the first dose (Cmax1) |  | Up to 7 days | 
| Peak serum concentration at steady-state (Cmaxss) |  | Up to 4 months | 
| Steady-state average serum concentration (Cavgss) |  | Up to 4 months | 
| Trough concentration (Ctrough) |  | At week 17 | 
| Incidence of adverse events (AEs) |  | Up to 2 years 3 months | 
| Incidence of serious adverse events (SAEs) |  | Up to 2 years 3 months | 
| Incidence of AEs leading to discontinuation |  | Up to 2 years | 
| Incidence of deaths |  | Up to 5 years | 
| Incidence of clinically significant changes in clinical laboratory results: Hematology tests |  | Up to 2 years 3 months | 
| Incidence of clinically significant changes in clinical laboratory results: Chemistry panel tests |  | Up to 2 years 3 months | 
| Efficacy parameters: disease control rate (DCR) by BICR with a minimum of 6 months follow-up |  | Up to 2 years 6 months | 
| Efficacy parameters: DCR by BICR with a minimum of 12 months follow-up |  | Up to 3 years | 
| Efficacy parameters: DCR by BICR at end of study |  | Up to 5 years | 
| Efficacy parameters: duration of response (DOR) by BICR with a minimum of 6 months follow-up |  | Up to 2 years 6 months | 
| Efficacy parameters: DOR by BICR with a minimum of 12 months follow-up |  | Up to 3 years | 
| Efficacy parameters: DOR by BICR at end of study |  | Up to 5 years | 
| Efficacy parameters: time to objective response (TTR) by BICR with a minimum of 6 months follow-up |  | Up to 2 years 6 months | 
| Efficacy parameters: TTR by BICR with a minimum of 12 months follow-up |  | Up to 3 years | 
| Efficacy parameters: TTR by BICR at end of study |  | Up to 5 years | 
| Efficacy parameters: progression-free survival (PFS) by BICR with a minimum of 6 months follow-up |  | Up to 2 years 6 months | 
| Efficacy parameters: PFS by BICR with a minimum of 12 months follow-up |  | Up to 3 years | 
| Efficacy parameters: PFS by BICR at end of study |  | Up to 5 years | 
| Efficacy parameters: overall survival (OS) with a minimum of 6 months follow-up |  | Up to 2 years 6 months | 
| Efficacy parameters: OS with a minimum of 12 months follow-up |  | Up to 3 years | 
| Efficacy parameters: OS at end of study |  | Up to 5 years | 
| Efficacy parameters: ORR by BICR with a minimum of 12 months follow-up |  | Up to 3 years | 
| Efficacy parameters: ORR by BICR at end of study |  | Up to 5 years | 
| Incidence of anaphylactic, hypersensitivity, and systemic infusion reactions/systemic injection reactions |  | Up to 2 years 3 months | 
| Incidence of local injection- or infusion-site reactions |  | Up to 2 years 3 months | 
| Percentage of participants who develop anti-nivolumab antibodies, if applicable |  | Up to 2 years 3 months | 
| Percentage of participants who develop neutralizing antibodies, if applicable |  | Up to 2 years 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BMS-936558, BMS-986298, Clear cell renal cell carcinoma, ccRCC, Nivolumab, Opdivo, rHuPH20, Subcutaneous