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: Active, not recruiting
• Conditions: Clear Cell Renal Cell Carcinoma
• Intervention / Treatment: Biological: Nivolumab; Biological: Nivolumab and rHuPH20

• Study Type: Interventional
• Enrollment (Actual): 681
• Phase: Phase 3

Expanded Access

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

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1426ANZ
    • Local Institution - 0038
  • San Juan, Argentina, J5402DIL
    • Local Institution - 0056
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, C1419AHN
      • Local Institution - 0095
    • Mar del Plata, Buenos Aires, Argentina, 7600
      • Local Institution - 0058
    • Pergamino, Buenos Aires, Argentina, B2700CPM
      • Local Institution - 0037
  • Córdoba Province
    • Parana, Córdoba Province, Argentina, 5000
      • Local Institution - 0079
    • Río Cuarto, Córdoba Province, Argentina, 5800
      • Local Institution - 0030
  • Río Negro Province
    • Viedma, Río Negro Province, Argentina, R8500ACE
      • Local Institution - 0066
• Brazil
  • Rio de Janeiro, Brazil, 20230-130
    • Local Institution - 0090
  • São Paulo, Brazil, 01246-000
    • Local Institution - 0081
  • São Paulo, Brazil, 01327-0001
    • Local Institution - 0096
  • Paraná
    • Curitiba, Paraná, Brazil, 80520-174
      • Local Institution - 0064
  • Rio Grande do Sul
    • Ijuí, Rio Grande do Sul, Brazil, 98700-000
      • Local Institution - 0107
    • Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
      • Local Institution - 0039
  • São Paulo
    • Barretos, São Paulo, Brazil, 014784-000
      • Local Institution - 0071
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Local Institution - 0070
• Chile
  • Región de Valparaíso
    • Viña del Mar, Región de Valparaíso, Chile, 2520598
      • Local Institution - 0077
  • Región de la Araucanía
    • Temuco, Región de la Araucanía, Chile
      • Local Institution - 0084
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile
      • Local Institution - 0005
    • Santiago, Santiago Metropolitan, Chile, 7500653
      • Local Institution - 0104
    • Santiago, Santiago Metropolitan, Chile, 7500921
      • Local Institution - 0076
• Czechia
  • Brno, Czechia, 656 53
    • Local Institution - 0063
  • Hradec Králové, Czechia, 500 05
    • Local Institution - 0036
  • Olomouc, Czechia, 77900
    • Local Institution - 0020
  • Ostrava, Czechia, 708 52
    • Local Institution - 0099
  • Prague, Czechia, 140 59
    • Local Institution - 0010
  • Praha 8 Liben, Czechia, 18081
    • Local Institution - 0106
• Finland
  • Tampere, Finland, 33521
    • Local Institution - 0017
• France
  • Nice, France, 6189
    • Local Institution
  • Suresnes, France, 92151
    • Local Institution - 0051
  • Villejuif, France, 94800
    • Local Institution - 0068
• Ireland
  • Dublin
    • Tallaght, Dublin, Ireland
      • Local Institution - 0060
• Italy
  • Cremona, Italy, 26100
    • Local Institution - 0033
  • Florence, Italy, 50134
    • Local Institution - 0008
  • Meldola, Italy, 47014
    • Local Institution - 0027
  • Milan, Italy, 20141
    • Local Institution - 0018
  • Milan, Italy, 20133
    • Local Institution
  • Padua, Italy, 35128
    • Local Institution - 0014
  • Parma, Italy, 43126
    • Local Institution - 0082
  • Pavia, Italy, 27100
    • Local Institution - 0092
  • Roma, Italy, 00168
    • Local Institution - 0100
  • Rome, Italy, 00152
    • Local Institution - 0091
  • Terni, Italy, 05100
    • Local Institution - 0057
• Mexico
  • Querétaro, Mexico, 76000
    • Local Institution - 0065
  • Querétaro, Mexico, 76090
    • Local Institution - 0085
  • San Luis Potosí City, Mexico, 78200
    • Local Institution - 0105
  • Coahuila
    • Torreón, Coahuila, Mexico, 27010
      • Local Institution - 0101
  • Mexico City
    • Tlalpan, Mexico City, Mexico, 14080
      • Local Institution - 0089
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Local Institution - 0103
    • Monterrey, Nuevo León, Mexico, 64710
      • Local Institution - 0031
• New Zealand
  • Auckland, New Zealand, 1023
    • Local Institution - 0053
  • Hamilton, New Zealand, 3204
    • Local Institution - 0041
  • Palmerston North, New Zealand, 4414
    • Local Institution - 0078
• Poland
  • Biała Podlaska, Poland, 21-500
    • Local Institution - 0055
  • Bydgoszcz, Poland, 85-796
    • Local Institution - 0062
  • Gdansk, Poland, 80-214
    • Local Institution - 0083
  • Krakow, Poland, 30-688
    • Local Institution - 0021
  • Krakow, Poland, 31-115
    • Local Institution - 0098
  • Poznan, Poland, 60-569
    • Local Institution - 0001
  • Warsaw, Poland, 02-781
    • Local Institution - 0023
• Portugal
  • Coimbra, Portugal, 3030-075
    • Local Institution - 0050
  • Lisbon, Portugal, 1500-650
    • Local Institution - 0052
• Romania
  • Bucharest, Romania, 022238
    • Local Institution - 0024
  • Cluj-Napoca, Romania, 400132
    • Local Institution - 0002
  • Cluj-Napoca, Romania, 400641
    • Local Institution - 0040
  • Craiova, Romania, 200347
    • Local Institution - 0016
• Russia
  • Chelyabinsk, Russia, 454087
    • SBIH Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine
  • Ivanovo, Russia, 153040
    • Ivanovo Regional Oncology Dispensary
  • Moscow, Russia, 125284
    • Hertzen Moscow Oncology Research Center
  • Nizghiy Novgorod, Russia, 603000
    • Local Institution
  • Omsk, Russia, 644013
    • Budgetary Healthcare Institution of Omsk Region - Clinical Oncological Dispensary
  • Saint Petersburg, Russia, 197022
    • LLC Eurocityclinic
• Spain
  • Barcelona, Spain, 08003
    • Local Institution - 0048
  • Barcelona, Spain, 08035
    • Local Institution - 0102
  • Barcelona, Spain, 08041
    • Local Institution - 0049
  • Madrid, Spain, 28026
    • Local Institution - 0072
  • Madrid, Spain, 28033
    • Local Institution - 0067
  • Madrid, Spain, 28046
    • Local Institution - 0074
  • Madrid, Spain, 28050
    • Local Institution - 0075
  • Sabadell, Spain, 08208
    • Local Institution - 0032
  • Santander, Spain, 39008
    • Local Institution - 0086
  • Seville, Spain, 31013
    • Local Institution - 0059
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06230
    • Local Institution - 0026
  • Ankara, Turkey (Türkiye), 06590
    • Local Institution - 0097
  • Istanbul, Turkey (Türkiye), 34098
    • Local Institution - 0019
  • Bagcilar
    • Istanbul, Bagcilar, Turkey (Türkiye), 34284
      • Local Institution - 0035
• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Local Institution
  • New York
    • Buffalo, New York, United States, 14263
      • Local Institution - 0025
  • Pennsylvania
    • West Reading, Pennsylvania, United States, 19611
      • 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 21, 2021
• Primary Completion (Actual): July 29, 2025
• Study Completion (Estimated): May 10, 2027

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 (Estimated): October 9, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: October 1, 2025

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: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Renal Cell; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; 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