An Investigational Immuno-therapy Study of Temozolomide Plus Radiation Therapy With Nivolumab or Placebo, for Newly Diagnosed Patients With Glioblastoma (GBM, a Malignant Brain Cancer) (CheckMate548)

• ClinicalTrials.gov Identifier: NCT02667587
• Recruitment Status: Active, not recruiting
• First Posted: January 29, 2016
• Last Update Posted: September 11, 2020
• Sponsor: Bristol-Myers Squibb
• Collaborator: Ono Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: January 26, 2016
• First Posted Date: January 29, 2016
• Last Update Posted Date: September 11, 2020
• Actual Study Start Date: May 5, 2016
• Estimated Primary Completion Date: February 11, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 4, 2019)

• Progression-free survival (PFS), Blinded Independent Central Review (BICR) assessed [ Time Frame: Approximately 35 months after first patient randomized ]
• Overall survival (OS) defined as time from the date of randomization to the date of death. [ Time Frame: Approximately 69 months after first patient randomized ]

• Original Primary Outcome Measures (submitted: January 26, 2016): Overall survival defined as time from the date of randomization to the date of death. [ Time Frame: Approximately 54 months after first patient first visit ]

Current Secondary Outcome Measures (submitted: January 14, 2019)

• Overall Survival (OS) [ Time Frame: up to 24 months ]
• Progression free survival (PFS), investigator assessed [ Time Frame: Approximately 35 months after first patient randomized ]

• Original Secondary Outcome Measures (submitted: January 26, 2016): Progression free survival, defined as the time from randomization to the date of the first documented tumor progression or death to any cause. [ Time Frame: Approximately 54 months after first patient first visit ]
• 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 Temozolomide Plus Radiation Therapy With Nivolumab or Placebo, for Newly Diagnosed Patients With Glioblastoma (GBM, a Malignant Brain Cancer)
• Official Title: A Randomized Phase 3 Single Blind Study of Temozolomide Plus Radiation Therapy Combined With Nivolumab or Placebo in Newly Diagnosed Adult Subjects With MGMT-Methylated (Tumor O6-methylguanine DNA Methyltransferase) Glioblastoma
• Brief Summary: The purpose of this study is to evaluate patients with glioblastoma that is MGMT-methylated (the MGMT gene is altered by a chemical change). Patients will receive temozolomide plus radiation therapy. They will be compared to patients receiving nivolumab in addition to temozolomide plus radiation therapy.
• 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: Brain Neoplasms

Intervention

• Drug: Nivolumab
  Other Names:

  • Opdivo
  • Nivo
  • N
  • BMS-936558
• Drug: Temozolomide
  Other Names:

  • Temodar
  • TMZ
  • Temodal
  • Temcad
• Radiation: Radiotherapy
  Other Name: RT
• Other: Nivolumab Placebo

Study Arms

• Experimental: Nivolumab + Temozolomide + Radiotherapy
  Nivolumab: specified dose on specified days; IV (intravenous) infusion Temozolomide: 75 mg (milligram)/meter squared daily during Radiotherapy, 4 week treatment break, 150 mg/meter squared Day 1-5 for Cycle 1 and increased to 200 mg/meter squared Day 1-5 for Cycle2-Cycle 6 as tolerated; orally (additional cycles may be permitted with approval of sponsor) Radiotherapy: 2 gray units (joule of radiation energy per kilogram) 5 times per week for 6 weeks
  Interventions:

  • Drug: Nivolumab
  • Drug: Temozolomide
  • Radiation: Radiotherapy
• Placebo Comparator: Nivolumab placebo + Temozolomide + Radiotherapy
  Nivolumab Placebo: specified dose on specified days; IV infusion Temozolomide: 75 mg/meter squared daily during Radiotherapy, 4 week treatment break, 150 mg/meter squared Day 1-5 for Cycle 1 and increased to 200 mg/meter squared Day 1-5 for Cycle2-Cycle 6 as tolerated; orally (additional cycles may be permitted with approval of sponsor) Radiotherapy: 2 gray units 5x/week x 6 weeks
  Interventions:

  • Drug: Temozolomide
  • Radiation: Radiotherapy
  • Other: Nivolumab Placebo

• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: June 26, 2017): 693
• Original Estimated Enrollment (submitted: January 26, 2016): 320
• Estimated Study Completion Date: August 1, 2023
• Estimated Primary Completion Date: February 11, 2022 (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:

• Males and Females, age ≥ 18 years old
• Newly diagnosed brain cancer or tumor called glioblastoma or GBM
• Karnofsky performance status of ≥ 70 (able to take care of self)
• Substantial recovery from surgery resection
• Tumor test result shows MGMT methylated or indeterminate tumor subtype

Exclusion Criteria:

• Biopsy-only of GBM with less than 20% of tumor removed
• 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

Other protocol defined inclusion/exclusion criteria could 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: NCT02667587
• Other Study ID Numbers: CA209-548; 2015-004722-34 ( 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
• Responsible Party: Bristol-Myers Squibb
• Study Sponsor: Bristol-Myers Squibb
• Collaborators: Ono Pharmaceutical Co. Ltd

Investigators

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

• PRS Account: Bristol-Myers Squibb
• Verification Date: September 2020