An Investigational Immuno-therapy Study of Nivolumab Compared to Temozolomide, Each Given With Radiation Therapy, for Newly-diagnosed Patients With Glioblastoma (GBM, a Malignant Brain Cancer) (CheckMate 498)

• ClinicalTrials.gov Identifier: NCT02617589
• Recruitment Status: Completed
• First Posted: December 1, 2015
• Results First Posted: February 3, 2021
• Last Update Posted: March 28, 2023
• Sponsor: Bristol-Myers Squibb
• Collaborator: Ono Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: November 26, 2015
• First Posted Date: December 1, 2015
• Results First Submitted Date: November 30, 2020
• Results First Posted Date: February 3, 2021
• Last Update Posted Date: March 28, 2023
• Actual Study Start Date: March 1, 2016
• Actual Primary Completion Date: January 17, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 15, 2021)

Overall Survival (OS) [ Time Frame: up to 3 years ]

OS is defined as the time between the date of randomization and the date of death due to any cause. A participant who has not died will be censored at the last known alive date.

Original Primary Outcome Measures (submitted: November 26, 2015)

Overall survival (OS) [ Time Frame: Approximately 3 years ]

Overall survival: Defined as the time between the date of randomization and the date of death due to any cause

Current Secondary Outcome Measures (submitted: March 1, 2023)

• Kaplan-Meier Plot of Progression Free Survival [ Time Frame: From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 6 years) ]
  PFS was defined as the time from randomization to the date of the first documented tumor progression or death due to any cause. Participants who did not have disease progression or who did not die were censored at the date of last tumor assessment. Participants who did not have any on study tumor assessment and did not have tumor progression or die were censored at the randomization date. Participants who started any subsequent anti-cancer therapy without a prior reported progression were censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. Participants who had surgical resection post start of study treatment were censored at the last tumor assessment date prior to initiation of surgical resection. PFS was determined by investigator reported response based on the Radiologic Assessment in Neuro-Oncology criteria.
• Overall Survival Rate at 24 Months [ Time Frame: At 24 Months ]
  The overall survival (OS) rate of (nivolumab + radiation therapy) and (temozolomide + radiation therapy) estimated as Kaplan-Meier probability of survival at 24 months. OS was defined as the time between the date of randomization and the date of death due to any cause. A participant who has not died was censored at the last known alive date.
• Overall Survival in Tumor Mutational Burden (TMB) High Population [ Time Frame: From randomization to the date of death due to any cause (up to approximately 6 years) ]
  OS in all randomized participants that are tumor mutational burden high. OS was defined as the time between the date of randomization and the date of death due to any cause. A participant who has not died was censored at the last known alive date.
• Progression Free Survival in Tumor Mutational Burden (TMB) High Population [ Time Frame: From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 6 years) ]
  PFS in all randomized participants that are tumor mutational burden high. PFS was defined as the time from randomization to the date of the first documented tumor progression or death due to any cause. Participants who did not have disease progression or who did not die were censored at the date of last tumor assessment. Participants who did not have any on study tumor assessment and did not have tumor progression or die were censored at the randomization date. Participants who started any subsequent anti-cancer therapy without a prior reported progression were censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. Participants who had surgical resection post start of study treatment were censored at the last tumor assessment date prior to initiation of surgical resection. PFS was determined by investigator reported response based on the Radiologic Assessment in Neuro-Oncology criteria.

Original Secondary Outcome Measures (submitted: November 26, 2015)

• Progression free survival (PFS) [ Time Frame: Approximately 24 months ]
  Progression free survival: Defined as the time from randomization to the date of the first documented tumor progression or death due to any cause
• Overall survival [ Time Frame: Approximately 24 months ]

• 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 Temozolomide, Each Given With Radiation Therapy, for Newly-diagnosed Patients With Glioblastoma (GBM, a Malignant Brain Cancer)
• Official Title: A Randomized Phase 3 Open Label Study of Nivolumab vs Temozolomide Each in Combination With Radiation Therapy in Newly Diagnosed Adult Subjects With Unmethylated MGMT (Tumor O-6-methylguanine DNA Methyltransferase) Glioblastoma (CheckMate 498: CHECKpoint Pathway and Nivolumab Clinical Trial Evaluation 498)
• Brief Summary: The purpose of this study is to evaluate patients with glioblastoma that is MGMT-unmethylated (the MGMT gene is not altered by a chemical change). Patients will receive Nivolumab every two weeks in addition to radiation therapy, and then every four weeks. They will be compared to patients receiving standard therapy with temozolomide in addition to radiation therapy.
• 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: Brain Cancer

Intervention

• Drug: Nivolumab
• Drug: Temozolomide
• Radiation: Radiotherapy

Study Arms

• Experimental: Nivolumab + Radiotherapy Arm
  Nivolumab IV infusion + Radiotherapy dose as specified
  Interventions:

  • Drug: Nivolumab
  • Radiation: Radiotherapy
• Active Comparator: Temozolomide + Radiotherapy Arm
  Temozolomide + Radiotherapy dose as specified
  Interventions:

  • Drug: Temozolomide
  • Radiation: Radiotherapy

• Publications *: Woroniecka K, Fecci PE. Immuno-synergy? Neoantigen vaccines and checkpoint blockade in glioblastoma. Neuro Oncol. 2020 Sep 29;22(9):1233-1234. doi: 10.1093/neuonc/noaa170. No abstract available.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 15, 2021): 560
• Original Estimated Enrollment (submitted: November 26, 2015): 550
• Actual Study Completion Date: March 4, 2022
• Actual Primary Completion Date: January 17, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Males and Females, age ≥ 18 years old
• Newly-diagnosed brain cancer or tumor called glioblastoma or GBM
• Tumor test result shows MGMT unmethylated type
• Karnofsky performance status of ≥ 70 (able to care for self)

Exclusion Criteria:

• Prior treatment for GBM (other than surgical resection)
• Any known tumor outside of the brain
• Recurrent or secondary GBM
• Active known or suspected autoimmune disease
• Biopsy with less than 20% of tumor removed

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: Australia, Austria, Belgium, Canada, Denmark, France, Germany, Israel, Italy, Japan, Netherlands, Norway, Poland, Russian Federation, Spain, Sweden, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT02617589
• Other Study ID Numbers: CA209-498; 2015-003739-37 ( 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: March 2023