Clinical trial NCT04810078: A Study of Subcutaneous Nivolumab Versus Intravenous Nivolumab in Participants With Previously Treated Clear Cell Renal Cell Carcinoma That is Advanced or Has Spread
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Clear Cell Renal Cell Carcinoma
Keywords: BMS-936558
BMS-986298
Clear cell renal cell carcinoma
ccRCC
Nivolumab
Opdivo
rHuPH20
Subcutaneous
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2021-03-22
Enrollment: 632
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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/exclusion criteria apply

Primary outcomes:
measure: Time-averaged serum concentration over 28 days (Cavgd28)
timeFrame: Up to 28 days
measure: Trough serum concentration at steady-state (Cminss)
timeFrame: Up to 4 months
Secondary outcomes:
measure: Objective response rate (ORR) by Blinded Independent Central Review (BICR) with a minimum of 6 months follow-up
timeFrame: Up to 2 years 6 months
measure: Trough serum concentration at day 28 (Cmind28)
timeFrame: At 28 days
measure: Maximum serum concentration after the first dose (Cmax1)
timeFrame: Up to 7 days
measure: Peak serum concentration at steady-state (Cmaxss)
timeFrame: Up to 4 months
measure: Steady-state average serum concentration (Cavgss)
timeFrame: Up to 4 months
measure: Trough concentration (Ctrough)
timeFrame: At week 17
measure: Incidence of adverse events (AEs)
timeFrame: Up to 2 years 3 months
measure: Incidence of serious adverse events (SAEs)
timeFrame: Up to 2 years 3 months
measure: Incidence of AEs leading to discontinuation
timeFrame: Up to 2 years
measure: Incidence of deaths
timeFrame: Up to 5 years
measure: Incidence of clinically significant changes in clinical laboratory results: Hematology tests
timeFrame: Up to 2 years 3 months
measure: Incidence of clinically significant changes in clinical laboratory results: Chemistry panel tests
timeFrame: Up to 2 years 3 months
measure: Efficacy parameters: disease control rate (DCR) by BICR with a minimum of 6 months follow-up
timeFrame: Up to 2 years 6 months
measure: Efficacy parameters: DCR by BICR with a minimum of 12 months follow-up
timeFrame: Up to 3 years
measure: Efficacy parameters: DCR by BICR at end of study
timeFrame: Up to 5 years
measure: Efficacy parameters: duration of response (DOR) by BICR with a minimum of 6 months follow-up
timeFrame: Up to 2 years 6 months
measure: Efficacy parameters: DOR by BICR with a minimum of 12 months follow-up
timeFrame: Up to 3 years
measure: Efficacy parameters: DOR by BICR at end of study
timeFrame: Up to 5 years
measure: Efficacy parameters: time to objective response (TTR) by BICR with a minimum of 6 months follow-up
timeFrame: Up to 2 years 6 months
measure: Efficacy parameters: TTR by BICR with a minimum of 12 months follow-up
timeFrame: Up to 3 years
measure: Efficacy parameters: TTR by BICR at end of study
timeFrame: Up to 5 years
measure: Efficacy parameters: progression-free survival (PFS) by BICR with a minimum of 6 months follow-up
timeFrame: Up to 2 years 6 months
measure: Efficacy parameters: PFS by BICR with a minimum of 12 months follow-up
timeFrame: Up to 3 years
measure: Efficacy parameters: PFS by BICR at end of study
timeFrame: Up to 5 years
measure: Efficacy parameters: overall survival (OS) with a minimum of 6 months follow-up
timeFrame: Up to 2 years 6 months
measure: Efficacy parameters: OS with a minimum of 12 months follow-up
timeFrame: Up to 3 years
measure: Efficacy parameters: OS at end of study
timeFrame: Up to 5 years
measure: Efficacy parameters: ORR by BICR with a minimum of 12 months follow-up
timeFrame: Up to 3 years
measure: Efficacy parameters: ORR by BICR at end of study
timeFrame: Up to 5 years
measure: Incidence of anaphylactic, hypersensitivity, and systemic infusion reactions/systemic injection reactions
timeFrame: Up to 2 years 3 months
measure: Incidence of local injection- or infusion-site reactions
timeFrame: Up to 2 years 3 months
measure: Percentage of participants who develop anti-nivolumab antibodies, if applicable
timeFrame: Up to 2 years 3 months
measure: Percentage of participants who develop neutralizing antibodies, if applicable
timeFrame: Up to 2 years 3 months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Local Institution
state: Illinois
city: Buffalo
country: United States
facility: Local Institution - 0025
state: New York
city: West Reading
country: United States
facility: Local Institution - 0088
state: Pennsylvania
city: Capital Federal
country: Argentina
facility: Local Institution - 0095
state: Buenos Aires
city: Mar Del Plata
country: Argentina
facility: Local Institution - 0058
state: Buenos Aires
city: Pergamino
country: Argentina
facility: Local Institution - 0037
state: Buenos Aires
city: Parana
country: Argentina
facility: Local Institution - 0079
state: Cordoba
city: Rio Cuarto
country: Argentina
facility: Local Institution - 0030
state: Cordoba
city: Viedma
country: Argentina
facility: Local Institution - 0066
state: RIO Negro
city: Buenos Aires
country: Argentina
facility: Local Institution - 0038
city: San Juan
country: Argentina
facility: Local Institution - 0056
city: Curitiba
country: Brazil
facility: Local Institution - 0064
state: Parana
city: Porto Alegre
country: Brazil
facility: Local Institution - 0039
state: RIO Grande DO SUL
city: Ijui
country: Brazil
facility: Local Institution - 0107
state: RS
city: Barretos
country: Brazil
facility: Local Institution - 0071
state: Sao Paulo
city: Sao Jose Do Rio Preto
country: Brazil
facility: Local Institution - 0070
state: Sao Paulo
city: Rio de Janeiro
country: Brazil
facility: Local Institution - 0090
city: Sao Paulo
country: Brazil
facility: Local Institution - 0081
city: Sao Paulo
country: Brazil
facility: Local Institution - 0096
city: Temuco
country: Chile
facility: Local Institution - 0084
state: Araucania
city: Santiago de Chile
country: Chile
facility: Local Institution - 0005
state: Metropolitana
city: Santiago de Chile
country: Chile
facility: Local Institution - 0104
state: Metropolitana
city: Santiago
country: Chile
facility: Local Institution - 0076
state: Metropolitana
city: Vina del Mar
country: Chile
facility: Local Institution - 0077
state: Valparaiso
city: Brno
country: Czechia
facility: Local Institution - 0063
city: Hradec Kralove
country: Czechia
facility: Local Institution - 0036
city: Olomouc
country: Czechia
facility: Local Institution - 0020
city: Ostrava
country: Czechia
facility: Local Institution - 0099
city: Prague
country: Czechia
facility: Local Institution - 0010
city: Praha 8 Liben
country: Czechia
facility: Local Institution - 0106
city: Tampere
country: Finland
facility: Local Institution - 0017
city: Nice cedex 2
country: France
facility: Local Institution
city: Suresnes
country: France
facility: Local Institution - 0051
city: Villejuif
country: France
facility: Local Institution - 0068
city: Tallaght
country: Ireland
facility: Local Institution - 0060
state: Dublin
city: Cremona
country: Italy
facility: Local Institution - 0033
city: Firenze
country: Italy
facility: Local Institution - 0008
city: Meldola
country: Italy
facility: Local Institution - 0027
city: Milano
country: Italy
facility: Local Institution
city: Milan
country: Italy
facility: Local Institution - 0018
city: Padova
country: Italy
facility: Local Institution - 0014
city: Parma
country: Italy
facility: Local Institution - 0082
city: Pavia
country: Italy
facility: Local Institution - 0092
city: Roma
country: Italy
facility: Local Institution - 0100
city: Rome
country: Italy
facility: Local Institution - 0091
city: Terni
country: Italy
facility: Local Institution - 0057
city: Torreon
country: Mexico
facility: Local Institution - 0101
state: Coahuila
city: Tlalpan
country: Mexico
facility: Local Institution - 0089
state: Distrito Federal
city: Monterrey
country: Mexico
facility: Local Institution - 0103
state: Nuevo LEON
city: Monterrey
country: Mexico
facility: Local Institution - 0031
state: Nuevo LEON
city: Queretaro
country: Mexico
facility: Local Institution - 0065
city: Queretaro
country: Mexico
facility: Local Institution - 0085
city: San Luis Potosi
country: Mexico
facility: Local Institution - 0105
city: Auckland
country: New Zealand
facility: Local Institution - 0053
city: Hamilton
country: New Zealand
facility: Local Institution - 0041
city: Palmerston North
country: New Zealand
facility: Local Institution - 0078
city: Biala Podlaska
country: Poland
facility: Local Institution - 0055
city: Bydgoszcz
country: Poland
facility: Local Institution - 0062
city: Gdansk
country: Poland
facility: Local Institution - 0083
city: Krakow
country: Poland
facility: Local Institution - 0021
city: Krakow
country: Poland
facility: Local Institution - 0098
city: Poznan
country: Poland
facility: Local Institution - 0001
city: Warszawa
country: Poland
facility: Local Institution - 0023
city: Coimbra
country: Portugal
facility: Local Institution - 0050
city: Lisboa
country: Portugal
facility: Local Institution - 0052
city: Bucuresti
country: Romania
facility: Local Institution - 0024
city: Cluj-Napoca
country: Romania
facility: Local Institution - 0002
city: Cluj-Napoca
country: Romania
facility: Local Institution - 0040
city: Craiova
country: Romania
facility: Local Institution - 0016
city: Chelyabinsk
country: Russian Federation
facility: SBIH Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine
city: Ivanovo
country: Russian Federation
facility: Ivanovo Regional Oncology Dispensary
city: Moscow
country: Russian Federation
facility: Hertzen Moscow Oncology Research Center
city: Nizghiy Novgorod
country: Russian Federation
facility: Local Institution
city: Omsk
country: Russian Federation
facility: Budgetary Healthcare Institution of Omsk Region - Clinical Oncological Dispensary
city: Saint Petersburg
country: Russian Federation
facility: LLC Eurocityclinic
city: Barcelona
country: Spain
facility: Local Institution - 0048
city: Barcelona
country: Spain
facility: Local Institution - 0102
city: Barcelona
country: Spain
facility: Local Institution - 0049
city: Madrid
country: Spain
facility: Local Institution - 0072
city: Madrid
country: Spain
facility: Local Institution - 0067
city: Madrid
country: Spain
facility: Local Institution - 0074
city: Madrid
country: Spain
facility: Local Institution - 0075
city: Sabadell
country: Spain
facility: Local Institution - 0032
city: Santander
country: Spain
facility: Local Institution - 0086
city: Sevilla
country: Spain
facility: Local Institution - 0059
city: Istanbul
country: Turkey
facility: Local Institution - 0035
state: Bagcilar
city: Ankara
country: Turkey
facility: Local Institution - 0026
city: Ankara
country: Turkey
facility: Local Institution - 0097
city: Istanbul
country: Turkey
facility: Local Institution - 0019
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: