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
• Results First Posted: February 3, 2022
• Last Update Posted: December 27, 2022
• 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
• Results First Submitted Date: November 30, 2021
• Results First Posted Date: February 3, 2022
• Last Update Posted Date: December 27, 2022
• Actual Study Start Date: May 9, 2016
• Actual Primary Completion Date: December 22, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 6, 2022)

• Progression-free Survival (PFS) Determined by BICR [ Time Frame: From randomization to the date of the first documented tumor progression or death by any cause. (up to approximately 4.5 years) ]
  The time from randomization to the date of the first documented tumor progression or death by any cause. PFS will be determined by a Blinded Independent Central Review (BICR) assessed based on Radiologic Assessment in Neuro-Oncology (RANO) criteria. Specifically, RANO response criteria indicates that within the first 12 weeks of completion of radiotherapy, progression can only be assessed if the majority of the new enhancement is outside of the radiation field or if there is pathologic confirmation of progressive disease.
• Overall Survival (OS) [ Time Frame: From randomization to date of death (up to approximately 4.5 years) ]
  The time from the date of randomization to the date of death. who have not died by the end of the study will be censored to last known date alive. OS is assessed in the randomized population with no corticosteroids at baseline population and in the overall randomized population.

• 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 6, 2022)

• Overall Survival (OS) Rates at 12 Months [ Time Frame: From randomization to 12 months after first dose ]
  Overall Survival (OS) rate is defined as the percentage of participants surviving at 12 months
• Overall Survival (OS) Rates at 24 Months [ Time Frame: From randomization to 24 months after first dose ]
  Overall Survival (OS) rate is defined as the percentage of participants surviving at 24 months
• Progression Free Survival (PFS) Based on Investigator Assessment [ Time Frame: From randomization to the date of the first documented tumor progression or death by any cause. (up to approximately 4.5 years) ]
  The time from randomization to the date of the first documented tumor progression or death by any cause. PFS will be determined by investigator assessment based Radiologic Assessment in Neuro-Oncology (RANO) criteria. Specifically, RANO response criteria indicates that within the first 12 weeks of completion of radiotherapy, progression can only be assessed if the majority of the new enhancement is outside of the radiation field or if there is pathologic confirmation of progressive disease.

• 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 *

• Lim M, Weller M, Idbaih A, Steinbach J, Finocchiaro G, Raval RR, Ansstas G, Baehring J, Taylor JW, Honnorat J, Petrecca K, De Vos F, Wick A, Sumrall A, Sahebjam S, Mellinghoff IK, Kinoshita M, Roberts M, Slepetis R, Warad D, Leung D, Lee M, Reardon DA, Omuro A. Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro Oncol. 2022 Nov 2;24(11):1935-1949. doi: 10.1093/neuonc/noac116.
• 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: Active, not recruiting
• Actual Enrollment (submitted: October 18, 2021): 716
• Original Estimated Enrollment (submitted: January 26, 2016): 320
• Estimated Study Completion Date: August 1, 2023
• Actual Primary Completion Date: December 22, 2020 (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
• 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: December 2022