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

Phase 3Active Not RecruitingNCT04810078

Bristol-Myers Squibb681 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

681

Conditions

Clear Cell Renal Cell Carcinoma

Interventions

Nivolumab and rHuPH20BIOLOGICAL

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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/exclusion criteria apply

Outcomes

Primary Outcomes

Time-averaged serum concentration over 28 days (Cavgd28)

Time frame: Up to 28 days

Trough serum concentration at steady-state (Cminss)

Time frame: Up to 4 months

Secondary Outcomes

Objective response rate (ORR) by Blinded Independent Central Review (BICR) with a minimum of 6 months follow-up

Time frame: Up to 2 years 6 months

Trough serum concentration at day 28 (Cmind28)

Time frame: At 28 days

Maximum serum concentration after the first dose (Cmax1)

Time frame: Up to 7 days

Peak serum concentration at steady-state (Cmaxss)

Time frame: Up to 4 months

Steady-state average serum concentration (Cavgss)

Time frame: Up to 4 months

Trough concentration (Ctrough)

Time frame: At week 17

Incidence of adverse events (AEs)

Time frame: Up to 2 years 3 months

Incidence of serious adverse events (SAEs)

Time frame: Up to 2 years 3 months

Incidence of AEs leading to discontinuation

Time frame: Up to 2 years

Incidence of deaths

Time frame: Up to 5 years

Incidence of clinically significant changes in clinical laboratory results: Hematology tests

Time frame: Up to 2 years 3 months

Incidence of clinically significant changes in clinical laboratory results: Chemistry panel tests

Time frame: Up to 2 years 3 months

Efficacy parameters: disease control rate (DCR) by BICR with a minimum of 6 months follow-up

Time frame: Up to 2 years 6 months

Efficacy parameters: DCR by BICR with a minimum of 12 months follow-up

Time frame: Up to 3 years

Efficacy parameters: DCR by BICR at end of study

Time frame: Up to 5 years

Efficacy parameters: duration of response (DOR) by BICR with a minimum of 6 months follow-up

Time frame: Up to 2 years 6 months

Efficacy parameters: DOR by BICR with a minimum of 12 months follow-up

Time frame: Up to 3 years

Efficacy parameters: DOR by BICR at end of study

Time frame: Up to 5 years

Efficacy parameters: time to objective response (TTR) by BICR with a minimum of 6 months follow-up

Time frame: Up to 2 years 6 months

Efficacy parameters: TTR by BICR with a minimum of 12 months follow-up

Time frame: Up to 3 years

Efficacy parameters: TTR by BICR at end of study

Time frame: Up to 5 years

Efficacy parameters: progression-free survival (PFS) by BICR with a minimum of 6 months follow-up

Time frame: Up to 2 years 6 months

Efficacy parameters: PFS by BICR with a minimum of 12 months follow-up

Time frame: Up to 3 years

Efficacy parameters: PFS by BICR at end of study

Time frame: Up to 5 years

Efficacy parameters: overall survival (OS) with a minimum of 6 months follow-up

Time frame: Up to 2 years 6 months

Efficacy parameters: OS with a minimum of 12 months follow-up

Time frame: Up to 3 years

Efficacy parameters: OS at end of study

Time frame: Up to 5 years

Efficacy parameters: ORR by BICR with a minimum of 12 months follow-up

Time frame: Up to 3 years

Efficacy parameters: ORR by BICR at end of study

Time frame: Up to 5 years

Incidence of anaphylactic, hypersensitivity, and systemic infusion reactions/systemic injection reactions

Time frame: Up to 2 years 3 months

Incidence of local injection- or infusion-site reactions

Time frame: Up to 2 years 3 months

Percentage of participants who develop anti-nivolumab antibodies, if applicable

Time frame: Up to 2 years 3 months

Percentage of participants who develop neutralizing antibodies, if applicable

Time frame: Up to 2 years 3 months

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

Overview

Conditions

Interventions

Eligibility

Locations (89)

Outcomes

Primary Outcomes

Secondary Outcomes