An Investigational Immuno-therapy Safety Trial of Nivolumab in Patients With Advanced or Metastatic Renal Cell Carcinoma (CheckMate 374)

• ClinicalTrials.gov Identifier: NCT02596035
• Recruitment Status: Completed
• First Posted: November 4, 2015
• Results First Posted: August 28, 2019
• Last Update Posted: October 27, 2022
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: November 2, 2015
• First Posted Date: November 4, 2015
• Results First Submitted Date: April 29, 2019
• Results First Posted Date: August 28, 2019
• Last Update Posted Date: October 27, 2022
• Actual Study Start Date: January 8, 2016
• Actual Primary Completion Date: March 19, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 23, 2019)

Percentage of Participants Who Experienced High-Grade (Grade 3-4 and Grade 5) Immune Mediated Adverse Events (IMAEs) [ Time Frame: Up to 100 days of the last dose of study drug (Approximately 2 years) ]

IMAEs were tabulated using worst grade per Common Terminology Criteria for Adverse Events, National Cancer Institute (NCI CTCAE) Version 4.0 criteria by system organ class and MedDRA version 20.1 preferred term.

Original Primary Outcome Measures (submitted: November 2, 2015)

Incidence of high grade (Grade 3-4 and Grade 5) IMAEs in subjects with advanced or metastatic renal cell carcinoma (RCC) who are treated with nivolumab monotherapy [ Time Frame: Approximately 2 years ]

IMAEs: skin, endocrinopathy, gastrointestinal, hepatic, renal, pulmonary and hypersensitivity reactions

Current Secondary Outcome Measures (submitted: October 25, 2022)

• Median Time to Onset of High Grade (Grade 3-5) Immune Mediated Adverse Events [ Time Frame: Up to 100 days of the last dose of study drug (Approximately 10 months up to 26 months) ]
  Time to onset was calculated from first dosing date to the event onset date. If a participant never experienced the given AE, the participant will be censored at the last contact date.
• Median Time to Resolution of High Grade (Grade 3-5) Immune Mediated Adverse Events [ Time Frame: From onset of grade 3-5 IMAEs to resolution of IMAEs (Approximately 4 years and 7 months) ]
  Time-to resolution of grade 3-5 AE was defined as the longest time from onset to complete resolution or improvement to the grade at baseline among all clustered select AEs in the category experienced by the participant. Events which worsened into grade 5 events (death) or have a resolution date equal to the date of death are considered unresolved. If a clustered AE is considered as unresolved, the resolution date will be censored to the last known date alive.
• Percentage of Participants Who Receive Immune Modulating Medication for the Immune-Mediated Event (Any Grade) [ Time Frame: Up to 100 days of the last dose of study drug (Approximately 3 years and 2 months) ]
  Immune modulating medication includes corticosteroids, infliximab, cyclophosphamide, Intravenous immunoglobulin (IVIG), and mycophenolate mofetil
• Percentage of Participants Who Receive More Than Equal to (>=) 40 mg Prednisone Equivalents for the Immune-Mediated Event [ Time Frame: Up to 100 days of the last dose of study drug (Approximately 3 years and 2 months) ]
  Immune modulating medication includes corticosteroids, infliximab, cyclophosphamide, Intravenous immunoglobulin (IVIG), and mycophenolate mofetil
• Total Duration of All Immune Modulating Medications Given for the Immune-Mediated Event [ Time Frame: From the initiation of Immune modulating medication to discontinuation (approximately 4 years and 9 months).) ]
  Immune modulating medication includes corticosteroids, infliximab, cyclophosphamide, Intravenous immunoglobulin (IVIG), and mycophenolate mofetil.
• Percentage of Participants With a Resolution of IMAEs After Initiating Immune Modulating Medication [ Time Frame: Up to 100 days of the last dose of study drug (Approximately 2 years) ]
  Percentage of participants with a resolution of IMAEs after initiating immune modulating medication.

Original Secondary Outcome Measures (submitted: November 2, 2015)

• Incidence of high grade (Grade 3-4 and Grade 5) IMAEs [ Time Frame: Approximately 2 years ]
• Median time to onset of high grade (Grade 3-4) IMAEs [ Time Frame: Approximately 2 years ]
  Median time to onset: Time to onset is calculated from first dosing date to the event onset date
• Median time to resolution of high grade (Grade 3-4) IMAEs [ Time Frame: Approximately 2 years ]
  Median time to resolution: Time to resolution is calculated from the adverse events (AE) onset date to AE end date
• Percentage of subjects who receive immune modulating medication for the immune-mediated event [ Time Frame: Approximately 2 years ]
  Immune modulating medication: corticosteroids, infliximab, cyclophosphamide, Intravenous immunoglobulin (IVIG), and mycophenolate mofetil
• Percentage of subjects who receive hormonal replacement therapy for the immune-mediated event [ Time Frame: Approximately 2 years ]
• Percentage of subjects who receive ≥ 40 mg prednisone equivalents for the immune-mediated event [ Time Frame: Approximately 2 years ]
• Total duration of all immune modulating medications given for the immune-mediated event [ Time Frame: Approximately 2 years ]

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

Descriptive Information

• Brief Title: An Investigational Immuno-therapy Safety Trial of Nivolumab in Patients With Advanced or Metastatic Renal Cell Carcinoma
• Official Title: A Phase 3b/4 Safety Trial of Nivolumab (BMS-936558) in Subjects With Advanced or Metastatic Renal Cell Carcinoma (CheckMate 374: CHECKpoint Pathway and Nivolumab Clinical Trial Evaluation 374)
• Brief Summary: This study will generate safety data on Nivolumab given by itself in treatment of advanced Renal Cell Carcinoma (RCC). The primary objective of this study is to assess immune related side effects, also known as immune-mediated adverse events (IMAEs), in patients treated with Nivolumab.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Renal Cell Carcinoma

Intervention

Drug: Nivolumab

Other Name: Opdivo

Study Arms

Experimental: Nivolumab

Nivolumab dose as specified

Intervention: Drug: Nivolumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 31, 2018): 197
• Original Estimated Enrollment (submitted: November 2, 2015): 150
• Actual Study Completion Date: May 24, 2021
• Actual Primary Completion Date: March 19, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Advanced or Metastatic renal cell carcinoma (RCC)

• Predominant clear cell histology:

  1. At least 1 but no more than 2 prior systemic anti vascular endothelial growth factor (anti-VEGF) treatments
  2. No more than 3 total prior systemic treatment regimens in the advanced or metastatic setting
  3. Subjects with prior treatment with a mechanistic target of rapamycin (mTOR) are eligible
• Non-clear cell histology: 0-3 prior systemic therapies and may include mTOR inhibitor
• Brain metastases allowed if asymptomatic, without edema, and not receiving corticosteroids or radiation
• Performance Status (PS): ≥ 70% Karnofsky Performance Scale (KPS)
• All Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic scores allowed

Exclusion Criteria:

• Subjects with any active autoimmune disease or a history of known autoimmune disease
• History of severe hypersensitivity reaction to other monoclonal antibodies
• Prior malignancy, active within the last 3 years, except for locally curable cancers which have been apparently cured
• Known HIV or AIDS-related illness
• Any positive tests for Hepatitis B or Hepatitis C virus indicating acute or chronic infection

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: United States

Administrative Information

• NCT Number: NCT02596035
• Other Study ID Numbers: CA209-374; 2015-003286-28 ( EudraCT Number )
• Has Data Monitoring Committee: No

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 2022