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 3

Recruiting

• Conditions: Clear Cell Renal Cell Carcinoma
• Interventions: Biological: Nivolumab and rHuPH20; Biological: Nivolumab

• Registration Number: NCT04810078
• Lead Sponsor: Bristol-Myers Squibb

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Study Timeline

• Study First Submitted: 2021-03-16
• Study First Submitted QC: 2021-03-19
• Study First Posted: 2021-03-22
• Study Start: 2021-05-21
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-13
• Last Update Posted: 2024-11-15
• Primary Completion: 2025-09-08
• Study Completion: 2026-01-29

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 632

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm D	Nivolumab and rHuPH20	-
Arm A	Nivolumab and rHuPH20	-
Arm C	Nivolumab and rHuPH20	-
Arm B	Nivolumab	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Objective response rate (ORR) by Blinded Independent Central Review (BICR) with a minimum of 6 months follow-up	Up to 2 years 6 months
Peak serum concentration at steady-state (Cmaxss)	Up to 4 months
Efficacy parameters: TTR by BICR at end of study	Up to 5 years
Maximum serum concentration after the first dose (Cmax1)	Up to 7 days
Trough concentration (Ctrough)	At week 17
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: 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
Trough serum concentration at day 28 (Cmind28)	At 28 days
Steady-state average serum concentration (Cavgss)	Up to 4 months
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
Efficacy parameters: disease control rate (DCR) 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: 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 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 neutralizing antibodies, if applicable	Up to 2 years 3 months
Efficacy parameters: OS with a minimum of 12 months follow-up	Up to 3 years
Percentage of participants who develop anti-nivolumab antibodies, if applicable	Up to 2 years 3 months

Trial Locations

Locations (92)

Local Institution; 🇹🇷 Izmir, Turkey

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

Local Institution - 0088; 🇺🇸 West Reading, Pennsylvania, United States

Instituto de Investigaciones Clinicas Mar del Plata; 🇦🇷 Mar Del Plata, Buenos Aires, Argentina

Centro de Investigacion Pergamino S.A.; 🇦🇷 Pergamino, Buenos Aires, Argentina

Instituto Oncologico de Cordoba IONC; 🇦🇷 Parana, Cordoba, Argentina

Cent Priv RMI Rio Cuarto SA II; 🇦🇷 Rio Cuarto, Cordoba, Argentina

Centro de Investigaciones Clinicas. Clinica Viedma S.A.; 🇦🇷 Viedma, RIO Negro, Argentina

Instituto Medico Especializado Alexander Fleming; 🇦🇷 Buenos Aires, Argentina

CER San Juan; 🇦🇷 San Juan, Argentina

Local Institution - 0064; 🇧🇷 Curitiba, Parana, Brazil

Local Institution - 0011; 🇧🇷 Ijui, RIO Grande DO SUL, Brazil

Local Institution - 0107; 🇧🇷 Ijui, Rio Grande Do Sul, Brazil

Local Institution - 0039; 🇧🇷 Porto Alegre, RIO Grande DO SUL, Brazil

Local Institution - 0071; 🇧🇷 Barretos, Sao Paulo, Brazil

Local Institution - 0070; 🇧🇷 Sao Jose Do Rio Preto, Sao Paulo, Brazil

Local Institution - 0090; 🇧🇷 Rio de Janeiro, Brazil

Hospital Sirio Libanes; 🇧🇷 Sao Paulo, Brazil

Local Institution - 0081; 🇧🇷 Sao Paulo, Brazil

Local Institution - 0096; 🇧🇷 Sao Paulo, Brazil

SIM Centro de Investigacion Clinica; 🇨🇱 Temuco, Araucania, Chile

Bradford Hill Centro de Investigacion Clinica; 🇨🇱 Santiago de Chile, Metropolitana, Chile

Centro de Estudios Clinicos SAGA; 🇨🇱 Santiago de Chile, Metropolitana, Chile

Fundacion Arturo Lopez Perez; 🇨🇱 Santiago, Metropolitana, Chile

Oncocentro Apys; 🇨🇱 Vina del Mar, Valparaiso, Chile

Local Institution - 0063; 🇨🇿 Brno, Czechia

Local Institution - 0036; 🇨🇿 Hradec Kralove, Czechia

Local Institution - 0020; 🇨🇿 Olomouc, Czechia

Local Institution - 0099; 🇨🇿 Ostrava, Czechia

Local Institution - 0010; 🇨🇿 Prague, Czechia

Local Institution - 0106; 🇨🇿 Praha 8 Liben, Czechia

Local Institution - 0080; 🇫🇮 Kuopio, Finland

Local Institution - 0017; 🇫🇮 Tampere, Finland

Local Institution - 0047; 🇫🇮 Turku, Finland

Local Institution - 0073; 🇫🇷 Lyon, France

Local Institution - 0051; 🇫🇷 Suresnes, France

Local Institution - 0068; 🇫🇷 Villejuif, France

Local Institution - 0060; 🇮🇪 Tallaght, Dublin, Ireland

Local Institution - 0033; 🇮🇹 Cremona, Italy

Local Institution - 0008; 🇮🇹 Firenze, Italy

Local Institution - 0027; 🇮🇹 Meldola, Italy

Local Institution - 0018; 🇮🇹 Milan, Italy

Local Institution - 0014; 🇮🇹 Padova, Italy

Local Institution - 0082; 🇮🇹 Parma, Italy

Local Institution - 0092; 🇮🇹 Pavia, Italy

Local Institution - 0100; 🇮🇹 Roma, Italy

Local Institution - 0091; 🇮🇹 Rome, Italy

Local Institution - 0057; 🇮🇹 Terni, Italy

Local Institution - 0101; 🇲🇽 Torreon, Coahuila, Mexico

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran; 🇲🇽 Tlalpan, Distrito Federal, Mexico

Local Institution - 0103; 🇲🇽 Monterrey, Nuevo LEON, Mexico

I Can Oncology Center; 🇲🇽 Monterrey, Nuevo LEON, Mexico

Cuidados Oncologicos; 🇲🇽 Queretaro, Mexico

Local Institution - 0085; 🇲🇽 Queretaro, Mexico

Centro de Atencion E Investigacion Cardiovascular Del Potosi S.C.; 🇲🇽 San Luis Potosi, Mexico

Auckland District Health Board-Auckland City Hospital; 🇳🇿 Auckland, New Zealand

Waikato Hospital; 🇳🇿 Hamilton, New Zealand

Palmerston North Hospital; 🇳🇿 Palmerston North, New Zealand

Local Institution - 0055; 🇵🇱 Biala Podlaska, Poland

Local Institution - 0062; 🇵🇱 Bydgoszcz, Poland

Local Institution - 0083; 🇵🇱 Gdansk, Poland

Local Institution - 0009; 🇵🇱 Gliwice, Poland

Local Institution - 0021; 🇵🇱 Krakow, Poland

Local Institution - 0098; 🇵🇱 Krakow, Poland

Local Institution - 0001; 🇵🇱 Poznan, Poland

Local Institution - 0023; 🇵🇱 Warszawa, Poland

Local Institution - 0050; 🇵🇹 Coimbra, Portugal

Local Institution - 0052; 🇵🇹 Lisboa, Portugal

Local Institution - 0024; 🇷🇴 Bucuresti, Romania

Local Institution - 0002; 🇷🇴 Cluj-Napoca, Romania

Local Institution - 0040; 🇷🇴 Cluj-Napoca, Romania

Local Institution - 0016; 🇷🇴 Craiova, Romania

SBIH Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine; 🇷🇺 Chelyabinsk, Russian Federation

Ivanovo Regional Oncology Dispensary; 🇷🇺 Ivanovo, Russian Federation

Local Institution - 0015; 🇷🇺 Moscow, Russian Federation

Hertzen Moscow Oncology Research Center; 🇷🇺 Moscow, Russian Federation

Budgetary Healthcare Institution of Omsk Region - Clinical Oncological Dispensary; 🇷🇺 Omsk, Russian Federation

LLC Eurocityclinic; 🇷🇺 Saint Petersburg, Russian Federation

Local Institution - 0048; 🇪🇸 Barcelona, Spain

Local Institution - 0102; 🇪🇸 Barcelona, Spain

Local Institution - 0049; 🇪🇸 Barcelona, Spain

Local Institution - 0072; 🇪🇸 Madrid, Spain

Local Institution - 0067; 🇪🇸 Madrid, Spain

Local Institution - 0074; 🇪🇸 Madrid, Spain

Local Institution - 0075; 🇪🇸 Madrid, Spain

Local Institution - 0032; 🇪🇸 Sabadell, Spain

Local Institution - 0086; 🇪🇸 Santander, Spain

Local Institution - 0059; 🇪🇸 Sevilla, Spain

Local Institution - 0026; 🇹🇷 Ankara, Turkey

Local Institution - 0097; 🇹🇷 Ankara, Turkey

Local Institution - 0019; 🇹🇷 Istanbul, Turkey

Local Institution - 0035; 🇹🇷 Istanbul, Turkey