A Study of Subcutaneous Nivolumab Versus Intravenous Nivolumab in Participants With Previously Treated Clear Cell Renal Cell Carcinoma That is Advanced or Has Spread (CheckMate-67T)

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

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 Overview

• Status: Recruiting
• Conditions: Clear Cell Renal Cell Carcinoma
• Intervention / Treatment: Biological: Nivolumab; Biological: Nivolumab and rHuPH20

• Study Type: Interventional
• Enrollment (Estimated): 632
• Phase: Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: BMS Study Connect Contact Center www.BMSStudyConnect.com; Phone Number: 855-907-3286; Email: Clinical.Trials@bms.com
• Study Contact Backup: Name: First line of the email MUST contain NCT # and Site #.

Study Locations

• Argentina
  • San Juan, Argentina, J5402DIL
    • Active, not recruiting
    • Local Institution - 0056
  • Buenos Aires
    • Ciudad Autonoma de BuenosAires, Buenos Aires, Argentina, C1426ANZ
      • Active, not recruiting
      • Local Institution - 0038
    • Mar Del Plata, Buenos Aires, Argentina, 7600
      • Active, not recruiting
      • Local Institution - 0058
    • Pergamino, Buenos Aires, Argentina, B2700CPM
      • Active, not recruiting
      • Local Institution - 0037
  • Cordoba
    • Parana, Cordoba, Argentina, 5000
      • Active, not recruiting
      • Local Institution - 0079
    • Rio Cuarto, Cordoba, Argentina, 5800
      • Recruiting
      • Cent Priv RMI Rio Cuarto SA II
      • Contact: Ignacio Magri, Site 0030; Phone Number: +5493585628491
  • RIO Negro
    • Viedma, RIO Negro, Argentina, 8500
      • Active, not recruiting
      • Local Institution - 0066
• Brazil
  • Rio de Janeiro, Brazil, 20230-130
    • Active, not recruiting
    • Local Institution - 0090
  • Sao Paulo, Brazil, 01.308-050
    • Active, not recruiting
    • Local Institution - 0095
  • Sao Paulo, Brazil, 01246-000
    • Active, not recruiting
    • Local Institution - 0081
  • Sao Paulo, Brazil, 01327-0001
    • Active, not recruiting
    • Local Institution - 0096
  • Parana
    • Curitiba, Parana, Brazil, 80520-174
      • Active, not recruiting
      • Local Institution - 0064
  • RIO Grande DO SUL
    • Ijui, RIO Grande DO SUL, Brazil, 98700-000
      • Withdrawn
      • Local Institution - 0011
    • Porto Alegre, RIO Grande DO SUL, Brazil, 91350-200
      • Active, not recruiting
      • Local Institution - 0039
  • Rio Grande Do Sul
    • Ijui, Rio Grande Do Sul, Brazil, 98700-000
      • Active, not recruiting
      • Local Institution - 0107
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 014784-000
      • Active, not recruiting
      • Local Institution - 0071
    • Sao Jose Do Rio Preto, Sao Paulo, Brazil, 15090-000
      • Active, not recruiting
      • Local Institution - 0070
• Chile
  • Araucania
    • Temuco, Araucania, Chile
      • Active, not recruiting
      • Local Institution - 0084
  • Metropolitana
    • Santiago, Metropolitana, Chile, 7500921
      • Active, not recruiting
      • Local Institution - 0076
    • Santiago de Chile, Metropolitana, Chile
      • Active, not recruiting
      • Local Institution - 0005
    • Santiago de Chile, Metropolitana, Chile, 7500653
      • Active, not recruiting
      • Local Institution - 0104
  • Valparaiso
    • Vina del Mar, Valparaiso, Chile, 2520598
      • Active, not recruiting
      • Local Institution - 0077
• Czechia
  • Brno, Czechia, 65653
    • Active, not recruiting
    • Local Institution - 0063
  • Hradec Kralove, Czechia, 500 05
    • Active, not recruiting
    • Local Institution - 0036
  • Olomouc, Czechia, 77900
    • Active, not recruiting
    • Local Institution - 0020
  • Ostrava, Czechia, 708 52
    • Active, not recruiting
    • Local Institution - 0099
  • Prague, Czechia, 140 59
    • Completed
    • Local Institution - 0010
  • Praha 8 Liben, Czechia, 18081
    • Completed
    • Local Institution - 0106
• Finland
  • Jyvaskyla, Finland, 40620
    • Withdrawn
    • Local Institution
  • Kuopio, Finland, 70029
    • Withdrawn
    • Local Institution - 0080
  • Tampere, Finland, 33521
    • Active, not recruiting
    • Local Institution - 0017
  • Turku, Finland, 20520
    • Withdrawn
    • Local Institution - 0047
• France
  • Lyon, France, 69373 CEDEX 08
    • Withdrawn
    • Local Institution - 0073
  • Nice cedex 2, France, 6189
    • Not yet recruiting
    • Local Institution
    • Contact: Site 0029
  • Suresnes, France, 92151
    • Active, not recruiting
    • Local Institution - 0051
  • Toulouse, France, 31059
    • Withdrawn
    • Local Institution
  • Villejuif, France, 94800
    • Active, not recruiting
    • Local Institution - 0068
• Ireland
  • Cork, Ireland, 1111
    • Withdrawn
    • Local Institution
  • Dublin, Ireland, 9
    • Withdrawn
    • Local Institution
  • Dublin
    • Tallaght, Dublin, Ireland
      • Active, not recruiting
      • Local Institution - 0060
• Italy
  • Cremona, Italy, 26100
    • Completed
    • Local Institution - 0033
  • Firenze, Italy, 50134
    • Active, not recruiting
    • Local Institution - 0008
  • Meldola, Italy, 47014
    • Active, not recruiting
    • Local Institution - 0027
  • Milano, Italy, 20133
    • Not yet recruiting
    • Local Institution
    • Contact: Site 0046
  • Milano, Italy, 20141
    • Completed
    • Local Institution - 0018
  • Padova, Italy, 35128
    • Active, not recruiting
    • Local Institution - 0014
  • Parma, Italy, 43126
    • Active, not recruiting
    • Local Institution - 0082
  • Pavia, Italy, 27100
    • Active, not recruiting
    • Local Institution - 0092
  • Pisa, Italy, 56126
    • Withdrawn
    • Local Institution
  • Roma, Italy, 00168
    • Active, not recruiting
    • Local Institution - 0100
  • Rome, Italy, 00152
    • Active, not recruiting
    • Local Institution - 0091
  • Terni, Italy, 05100
    • Active, not recruiting
    • Local Institution - 0057
• Mexico
  • Queretaro, Mexico, 76000
    • Completed
    • Local Institution - 0065
  • Queretaro, Mexico, 76090
    • Active, not recruiting
    • Local Institution - 0085
  • San Luis Potosi, Mexico, 78200
    • Active, not recruiting
    • Local Institution - 0105
  • Coahuila
    • Torreon, Coahuila, Mexico, 27010
      • Active, not recruiting
      • Local Institution - 0101
  • Distrito Federal
    • Tlalpan, Distrito Federal, Mexico, 14080
      • Active, not recruiting
      • Local Institution - 0089
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64460
      • Active, not recruiting
      • Local Institution - 0103
    • Monterrey, Nuevo LEON, Mexico, 64710
      • Active, not recruiting
      • Local Institution - 0031
• New Zealand
  • Auckland, New Zealand, 1023
    • Recruiting
    • Auckland District Health Board-Auckland City Hospital
    • Contact: Simon Fu, Site 0053; Phone Number: 6493074949
  • Hamilton, New Zealand, 3204
    • Recruiting
    • Waikato Hospital
    • Contact: Alvin Tan, Site 0041; Phone Number: 6478398899
  • Palmerston North, New Zealand, 4414
    • Recruiting
    • Palmerston North Hospital
    • Contact: Navin Wewala, Site 0078; Phone Number: 6463509159
• Poland
  • Biala Podlaska, Poland, 21-500
    • Active, not recruiting
    • Local Institution - 0055
  • Bydgoszcz, Poland, 85-796
    • Active, not recruiting
    • Local Institution - 0062
  • Gdansk, Poland, 80-214
    • Active, not recruiting
    • Local Institution - 0083
  • Gliwice, Poland, 44-101
    • Withdrawn
    • Local Institution - 0009
  • Krakow, Poland, 30-688
    • Active, not recruiting
    • Local Institution - 0021
  • Krakow, Poland, 31-115
    • Active, not recruiting
    • Local Institution - 0098
  • Poznan, Poland, 60-569
    • Active, not recruiting
    • Local Institution - 0001
  • Warszawa, Poland, 02-781
    • Active, not recruiting
    • Local Institution - 0023
• Portugal
  • Coimbra, Portugal, 3030-075
    • Active, not recruiting
    • Local Institution - 0050
  • Lisboa, Portugal, 1500-650
    • Active, not recruiting
    • Local Institution - 0052
• Romania
  • Bucuresti, Romania, 022238
    • Active, not recruiting
    • Local Institution - 0024
  • Cluj-Napoca, Romania, 400132
    • Active, not recruiting
    • Local Institution - 0002
  • Cluj-Napoca, Romania, 400461
    • Active, not recruiting
    • Local Institution - 0040
  • Craiova, Romania, 200347
    • Active, not recruiting
    • Local Institution - 0016
• Russian Federation
  • Chelyabinsk, Russian Federation, 454087
    • Terminated
    • SBIH Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine
  • Ivanovo, Russian Federation, 153040
    • Terminated
    • Ivanovo Regional Oncology Dispensary
  • Moscow, Russian Federation, 115478
    • Withdrawn
    • Local Institution
  • Moscow, Russian Federation, 117997
    • Withdrawn
    • Local Institution
  • Moscow, Russian Federation, 121359
    • Withdrawn
    • Local Institution
  • Moscow, Russian Federation, 125284
    • Active, not recruiting
    • Hertzen Moscow Oncology Research Center
  • Moscow, Russian Federation, 121309
    • Withdrawn
    • Local Institution - 0015
  • Nizghiy Novgorod, Russian Federation, 603000
    • Terminated
    • Local Institution
  • Omsk, Russian Federation, 644013
    • Terminated
    • Budgetary Healthcare Institution of Omsk Region - Clinical Oncological Dispensary
  • Saint Petersburg, Russian Federation, 197022
    • Terminated
    • LLC Eurocityclinic
• Spain
  • Barcelona, Spain, 08003
    • Completed
    • Local Institution - 0048
  • Barcelona, Spain, 08035
    • Active, not recruiting
    • Local Institution - 0102
  • Barcelona, Spain, 08041
    • Completed
    • Local Institution - 0049
  • Madrid, Spain, 28026
    • Active, not recruiting
    • Local Institution - 0072
  • Madrid, Spain, 28033
    • Completed
    • Local Institution - 0067
  • Madrid, Spain, 28046
    • Active, not recruiting
    • Local Institution - 0074
  • Madrid, Spain, 28050
    • Active, not recruiting
    • Local Institution - 0075
  • Sabadell, Spain, 08208
    • Completed
    • Local Institution - 0032
  • Santander, Spain, 39008
    • Completed
    • Local Institution - 0086
  • Sevilla, Spain, 31013
    • Active, not recruiting
    • Local Institution - 0059
• Turkey
  • Adana, Turkey, 1123
    • Withdrawn
    • Local Institution
  • Ankara, Turkey, 06230
    • Active, not recruiting
    • Local Institution - 0026
  • Ankara, Turkey, 06590
    • Active, not recruiting
    • Local Institution - 0097
  • Istanbul, Turkey, 34098
    • Active, not recruiting
    • Local Institution - 0019
  • Istanbul, Turkey, 34214
    • Active, not recruiting
    • Local Institution - 0035
  • Izmir, Turkey, 111
    • Withdrawn
    • Local Institution
• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Not yet recruiting
      • Local Institution
      • Contact: Site 0045
  • New York
    • Buffalo, New York, United States, 14263
      • Active, not recruiting
      • Local Institution - 0025
  • Pennsylvania
    • West Reading, Pennsylvania, United States, 19611
      • Active, not recruiting
      • Local Institution - 0088

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A	Biological: Nivolumab and rHuPH20; Specified dose on specified days; Other Names: BMS-986298
Active Comparator: Arm B	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo
Experimental: Arm C	Biological: Nivolumab and rHuPH20; Specified dose on specified days; Other Names: BMS-986298
Experimental: Arm D	Biological: Nivolumab and rHuPH20; Specified dose on specified days; Other Names: BMS-986298

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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
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 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
Trough concentration (Ctrough)	At week 17
Incidence of anaphylactic, hypersensitivity, and systemic infusion reactions/systemic injection reactions	Up to 2 years 3 months

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2021
• Primary Completion (Estimated): September 8, 2025
• Study Completion (Estimated): January 29, 2026

Study Registration Dates

• First Submitted: March 16, 2021
• First Submitted That Met QC Criteria: March 19, 2021
• First Posted (Actual): March 22, 2021

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Nivolumab; Subcutaneous; Opdivo; ccRCC; BMS-936558; rHuPH20; BMS-986298; Clear cell renal cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CA209-67T; 2020-003655-15 (EudraCT Number); U1111-1255-9514 (Registry Identifier: WHO)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No