Clear Cell Renal Cell Carcinoma
Conditions
Keywords
BMS-936558, BMS-986298, Clear cell renal cell carcinoma, ccRCC, Nivolumab, Opdivo, rHuPH20, Subcutaneous
Brief summary
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.
Interventions
BIOLOGICALNivolumab and rHuPH20
Specified dose on specified days
BIOLOGICALNivolumab
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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: 1. They have received established antiretroviral therapy (ART) for at least 4 weeks prior to randomization 2. They continue on ART as clinically indicated while enrolled on study 3. CD4 counts and viral load are monitored per standard of care by a local health care provider 4. 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Trough serum concentration at steady-state (Cminss) | Up to 4 months |
| Time-averaged serum concentration over 28 days (Cavgd28) | Up to 28 days |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Objective response rate (ORR) by Blinded Independent Central Review (BICR) with a minimum of 6 months follow-up | Up to 2 years 6 months |
| 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 |
| Efficacy parameters: DOR by BICR at end of study | Up to 5 years |
| Trough serum concentration at day 28 (Cmind28) | At 28 days |
Countries
Argentina, Brazil, Chile, Czechia, Finland, France, Ireland, Italy, Mexico, New Zealand, Poland, Portugal, Romania, Russia, Spain, Turkey (Türkiye), United States
Outcome results
None listed