An Investigational Immuno-therapy Study of Nivolumab, Compared to Placebo, in Patients With Bladder or Upper Urinary Tract Cancer, Following Surgery to Remove the Cancer (CheckMate 274)

• ClinicalTrials.gov Identifier: NCT02632409
• Recruitment Status: Active, not recruiting
• First Posted: December 16, 2015
• Results First Posted: December 1, 2021
• Last Update Posted: January 8, 2024
• Sponsor: Bristol-Myers Squibb
• Collaborator: Ono Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: December 14, 2015
• First Posted Date: December 16, 2015
• Results First Submitted Date: July 16, 2021
• Results First Posted Date: December 1, 2021
• Last Update Posted Date: January 8, 2024
• Actual Study Start Date: March 22, 2016
• Actual Primary Completion Date: July 17, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 5, 2021)

• Disease Free Survival (DFS) [ Time Frame: approximately up to 48 months ]
  The time between the date of randomization and the date of first documented recurrence (local urothelial tract, local non-urothelial tract or distant), or death due to any cause, whichever occurs first.
• Disease Free Survival (DFS) in PD-L1 Expression ≥ 1% Population [ Time Frame: approximately up to 48 months ]
  The time between the date of randomization and the date of first documented recurrence (local urothelial tract, local non-urothelial tract or distant), or death due to any cause, whichever occurs first.

Original Primary Outcome Measures (submitted: December 15, 2015)

Disease free survival (DFS) [ Time Frame: Approximately 5 years after the first subject is randomized ]

DFS defined as the time between the date of randomization and the date of first recurrence or death (of any cause) whichever occurs first.

Current Secondary Outcome Measures (submitted: November 5, 2021)

• Non-Urothelial Tract Recurrence Free Survival [ Time Frame: up to 53 months ]
  The time between the date of randomization and the date of first documented recurrence (local non-urothelial tract or distant), or death due to any cause, whichever occurs first.
• Non-Urothelial Tract Recurrence Free Survival in PD-L1 Expression ≥ 1% Population [ Time Frame: up to 53 months ]
  The time between the date of randomization and the date of first documented recurrence (local non-urothelial tract or distant), or death due to any cause, whichever occurs first.
• Overall Survival [ Time Frame: on going ]
  the time from randomization to the date of death from any cause.
• Overall Survival in Participants With PD-L1 Expression ≥ 1% [ Time Frame: on going ]
  the time from randomization to the date of death from any cause.
• Disease Specific Survival [ Time Frame: on going ]
  the time from randomization to the date of death due to disease (urothelial cancer).
• Disease Specific Survival in Participants With PD-L1 Expression ≥ 1% [ Time Frame: on going ]
  the time from randomization to the date of death due to disease (urothelial cancer).

Original Secondary Outcome Measures (submitted: December 15, 2015)

• Non-Urothelial track recurrence free survival (NUTRFS) [ Time Frame: Approximately 5 years after the first subject is randomized ]
  NUTRFS is defined as the time between the date of randomization and the date of first local non urothelial tract or distant recurrence or death (of any cause), whichever occurs first.
• Disease specific survival (DSS) [ Time Frame: Approximately 5 years after the first subject is randomized ]
  DSS is defined the time between the date of randomization and the date of death due to disease (urothelial cancer).
• Overall survival (OS) [ Time Frame: Approximately 5 years after the first subject is randomized ]
  OS is defined as the time between the date of randomization and the date of death (of any cause).

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

Descriptive Information

• Brief Title: An Investigational Immuno-therapy Study of Nivolumab, Compared to Placebo, in Patients With Bladder or Upper Urinary Tract Cancer, Following Surgery to Remove the Cancer
• Official Title: A Phase 3 Randomized, Double-blind, Multi-center Study of Adjuvant Nivolumab Versus Placebo in Subjects With High Risk Invasive Urothelial Carcinoma (CheckMate 274: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 274)
• Brief Summary: The purpose of this study is to determine the effectiveness and safety of Nivolumab compared to placebo in participants who have undergone radical surgery for invasive urothelial cancer.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Various Advanced Cancer

Intervention

• Biological: Nivolumab
• Other: Placebo

Study Arms

• Experimental: Nivolumab
  Nivolumab dose as specified
  Intervention: Biological: Nivolumab
• Placebo Comparator: Placebo
  Placebo dose as specified
  Intervention: Other: Placebo

• Publications *: Bajorin DF, Witjes JA, Gschwend JE, Schenker M, Valderrama BP, Tomita Y, Bamias A, Lebret T, Shariat SF, Park SH, Ye D, Agerbaek M, Enting D, McDermott R, Gajate P, Peer A, Milowsky MI, Nosov A, Neif Antonio J Jr, Tupikowski K, Toms L, Fischer BS, Qureshi A, Collette S, Unsal-Kacmaz K, Broughton E, Zardavas D, Koon HB, Galsky MD. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2021 Jun 3;384(22):2102-2114. doi: 10.1056/NEJMoa2034442. Erratum In: N Engl J Med. 2021 Aug 26;385(9):864.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 5, 2021): 709
• Original Estimated Enrollment (submitted: December 15, 2015): 640
• Estimated Study Completion Date: May 27, 2027
• Actual Primary Completion Date: July 17, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Must have had invasive urothelial cancer at high risk of recurrence originating in the bladder, ureter, or renal pelvis
• Must have had radical surgical resection (e.g. radical cystectomy), performed within the last 120 days
• Must have disease free status as determined by imaging within 4 weeks of dosing
• Tumor tissue must be provided for biomarker analysis
• Patients who have not received prior neoadjuvant cisplatin chemotherapy must be ineligible for or refuse cisplatin-based adjuvant chemotherapy

Exclusion Criteria:

• Partial bladder or partial kidney removal (eg, partial cystectomy or partial nephrectomy)
• Secondary Treatment (eg, adjuvant systemic chemotherapy for bladder cancer) following surgical removal of bladder cancer
• Subjects with active, known or suspected autoimmune disease
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured
• Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 day of study drug administration
• Positive test for hepatitis B virus surface antigen (HBV s Ag) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection

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, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Denmark, France, Germany, Greece, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Peru, Poland, Romania, Russian Federation, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT02632409
• Other Study ID Numbers: CA209-274; 2014-003626-40 ( EudraCT Number )
• 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: Ono Pharmaceutical Co. Ltd

Investigators

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

• PRS Account: Bristol-Myers Squibb
• Verification Date: January 2024