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)

• ClinicalTrials.gov Identifier: NCT04810078
• Recruitment Status: Active, not recruiting
• First Posted: March 22, 2021
• Last Update Posted: October 12, 2023
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: March 16, 2021
• First Posted Date: March 22, 2021
• Last Update Posted Date: October 12, 2023
• Actual Study Start Date: May 24, 2021
• Estimated Primary Completion Date: September 8, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 16, 2021)

• 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 ]

• Original Primary Outcome Measures (submitted: March 19, 2021): Minimum serum concentration at Day 28 (Cmind28) [ Time Frame: Up to 28 days ]

Current Secondary Outcome Measures (submitted: June 29, 2023)

• 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 ]

Original Secondary Outcome Measures (submitted: March 19, 2021)

• 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 ]
• Average serum concentration over 28 days (Cavgd28) [ Time Frame: Up to 28 days ]
• Maximum serum concentration after the first dose (Cmax1) [ Time Frame: Up to 7 days ]
• Time to maximum concentration (Tmax) [ Time Frame: Up to 7 days ]
• Steady-state average serum concentration (Cavgss) [ Time Frame: Up to 4 months ]
• Steady-state trough serum concentration (Cminss) [ Time Frame: Up to 4 months ]
• 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 [ 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 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Clear Cell Renal Cell Carcinoma

Intervention

• Biological: Nivolumab and rHuPH20
  Specified dose on specified days
  Other Name: BMS-986298
• Biological: Nivolumab
  Specified dose on specified days
  Other Names:

  • Opdivo
  • BMS-936558

Study Arms

• Experimental: Arm A: Subcutaneous Nivolumab
  Intervention: Biological: Nivolumab and rHuPH20
• Active Comparator: Arm B: Intravenous Nivolumab
  Intervention: Biological: Nivolumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: March 19, 2021): 454
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 29, 2026
• Estimated Primary Completion Date: September 8, 2025 (Final data collection date for primary outcome measure)

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 on the study
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, Chile, Czechia, Finland, France, Ireland, Italy, Mexico, New Zealand, Poland, Portugal, Romania, Russian Federation, Spain, Turkey, United States

Administrative Information

• NCT Number: NCT04810078
• Other Study ID Numbers: CA209-67T; 2020-003655-15 ( EudraCT Number ); U1111-1255-9514 ( Registry Identifier: WHO )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: October 2023