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)

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)

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.

Study Overview

• Status: Completed
• Conditions: Brain Cancer
• Intervention / Treatment: Drug: Temozolomide; Radiation: Radiotherapy; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 560
• Phase: Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales, Australia, 2170
    • Local Institution - 0002
  • New South Wales
    • St. Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Local Institution - 0003
    • Prahran, Victoria, Australia, 3181
      • Local Institution - 0004
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Local Institution - 0001
• Austria
  • Linz, Austria, 4020
    • Local Institution - 0061
  • Vienna, Austria, 1090
    • Local Institution - 0060
• Belgium
  • Brussels, Belgium, 1090
    • Universitair Ziekenhuis Brussel
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Leuven, Belgium, 3000
    • UZ Leuven
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer - Vancouver
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute and Hospital
• Denmark
  • Copenhagen, Denmark, 2100
    • Local Institution
  • Odense, Denmark, 5000
    • Local Institution
• France
  • Bron Cedex, France, 69677
    • Local Institution - 0032
  • Lille Cedex, France, 59037
    • Local Institution
  • Marseille, France, 13005
    • Local Institution - 0024
  • Nancy, France, 54035
    • Local Institution - 0101
  • Paris, France, 75010
    • Local Institution - 0023
  • Paris cedex 13, France, 75651
    • Local Institution - 0038
  • Rennes, France, 35000
    • Centre Eugene Marquis
  • Toulouse, France, 31100
    • Local Institution - 0106
• Germany
  • Bonn, Germany, 53105
    • Local Institution - 0051
  • Erlangen, Germany, 91054
    • Local Institution - 0072
  • Frankfurt am Main, Germany, 60528
    • Local Institution - 0049
  • Freiburg, Germany, 79106
    • Local Institution - 0073
  • Hamburg, Germany, 20246
    • Local Institution - 0054
  • Heidelberg, Germany, 69120
    • Local Institution - 0052
  • Koeln, Germany, 50937
    • Local Institution - 0139
  • Muenster, Germany, 48149
    • Local Institution - 0050
  • Munich, Germany, 81675
    • Local Institution - 0138
  • Regensburg, Germany, 93053
    • Local Institution - 0055
  • Tuebingen, Germany, 72076
    • Local Institution - 0056
• Israel
  • Petach Tikva, Israel, 49100
    • Local Institution - 0096
  • Tel Aviv, Israel, 64239
    • Local Institution - 0097
• Italy
  • Bologna, Italy, 40139
    • Local Institution - 0076
  • Milano, Italy, 20133
    • Local Institution - 0079
  • Padova, Italy, 35128
    • Local Institution - 0126
  • Rozzano (milano), Italy, 20089
    • Local Institution - 0135
  • Siena, Italy, 53100
    • Local Institution - 0078
  • Torino, Italy, 10126
    • Local Institution - 0077
• Japan
  • Tokyo, Japan, 1628666
    • Local Institution - 0112
  • Aichi
    • Nagoya-shi, Aichi, Japan, 4668560
      • Local Institution - 0115
  • Chiba
    • Chiba-shi, Chiba, Japan, 2608677
      • Local Institution - 0125
  • Hiroshima
    • Hiroshima-Shi, Hiroshima, Japan, 7348551
      • Local Institution - 0123
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 0608648
      • Local Institution - 0122
  • Hyogo
    • Kobe, Hyogo, Japan, 6500017
      • Local Institution - 0129
  • Ibaraki
    • Tsukuba-shi, Ibaraki, Japan, 3058576
      • Local Institution - 0111
  • Ishikawa
    • Kanazawa-shi, Ishikawa, Japan, 9200934
      • Local Institution - 0121
  • Kagoshima
    • Kagoshima-shi, Kagoshima, Japan, 8908520
      • Local Institution - 0131
  • Kanagawa
    • Sagamihara-shi, Kanagawa, Japan, 2520375
      • Local Institution - 0133
  • Kumamoto
    • Kumamoto-shi, Kumamoto, Japan, 8608556
      • Local Institution - 0119
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 606-8507
      • Local Institution - 0117
    • Kyoto-shi, Kyoto, Japan, 6128555
      • Local Institution - 0116
  • Okayama
    • Okayama-shi, Okayama, Japan, 7008558
      • Local Institution - 0134
  • Osaka
    • Hirakata-shi, Osaka, Japan, 5731191
      • Local Institution
    • Suita-shi, Osaka, Japan, 565-0871
      • Local Institution - 0130
  • Saitama
    • Hidaka, Saitama, Japan, 350-1298
      • Local Institution - 0113
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 1138655
      • Local Institution - 0128
    • Chuo-ku, Tokyo, Japan, 1040045
      • Local Institution - 0114
    • Mitaka-shi, Tokyo, Japan, 181-8611
      • Local Institution - 0118
  • Yamagata
    • Yamagata-shi, Yamagata, Japan, 9909585
      • Local Institution - 0110
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • NKI AVL
  • Groningen, Netherlands, 9713 AP
    • Universitair Medisch Centrum Groningen
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus MC
  • Utrecht, Netherlands, 3584CX
    • Local Institution - 0063
• Norway
  • Oslo, Norway, 0379
    • Local Institution
• Poland
  • Gdansk, Poland, 80952
    • Local Institution - 0080
  • Warszawa, Poland, 02-781
    • Local Institution - 0081
• Russian Federation
  • Moscow, Russian Federation, 105229
    • Local Institution - 0070
  • Moscow, Russian Federation, 115478
    • Local Institution - 0105
• Spain
  • Badalona-Barcelona, Spain, 08916
    • Local Institution
  • Barcelona, Spain, 08035
    • Local Institution
  • Barcelona, Spain, 08036
    • Local Institution - 0028
  • Madrid, Spain, 28041
    • Local Institution
  • Madrid, Spain, 28007
    • Local Institution - 0029
  • Santiago De Compostela, Spain, 15706
    • Local Institution
  • Valencia, Spain, 46014
    • Local Institution - 0025
• Sweden
  • Lund, Sweden, 221 85
    • Local Institution
  • Solna, Sweden, 171 64
    • Local Institution
• Switzerland
  • Geneve, Switzerland, 1211
    • Local Institution - 0059
  • Lausanne, Switzerland, 1011
    • Local Institution - 0057
  • Zuerich, Switzerland, 8091
    • Local Institution - 0053
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Beaston West of Scotland Cancer Centre
  • Greater London
    • London, Greater London, United Kingdom, NW1 2PG
      • University College Hospital
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M20 4BX
      • Christie Hospital Nhs Found. Trust
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Royal Marsden Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3410
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Local Institution - 0083
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Los Angeles, California, United States, 90095-1769
      • Local Institution - 0019
    • Sacramento, California, United States, 95816
      • Sutter Institute for Medical Research
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital
    • San Francisco, California, United States, 94143-0372
      • The Regents of the University of California, San Francisco
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Comprehensive Cancer Center
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University - Winship Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Local Institution - 0006
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School OF Medicine-Siteman Cancer Center
  • New Jersey
    • Edison, New Jersey, United States, 08820
      • JFK Medical Center
    • Hackensack, New Jersey, United States, 07601
      • Local Institution - 0064
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center (CUMC)
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
    • Durham, North Carolina, United States, 27710
      • Preston Robert Tisch Brain Tumor Center at Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Local Institution - 0010
    • Columbus, Ohio, United States, 43210
      • Local Institution - 0095
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Local Institution - 0132
    • Philadelphia, Pennsylvania, United States, 19107
      • Local Institution - 0007
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Local Institution - 0090
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390-8852
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • University Of Texas Md Anderson Cancer Ctr
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Local Institution - 0068
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Neuroscience Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab + Radiotherapy Arm; Nivolumab IV infusion + Radiotherapy dose as specified	Radiation: Radiotherapy; Drug: Nivolumab
Active Comparator: Temozolomide + Radiotherapy Arm; Temozolomide + Radiotherapy dose as specified	Drug: Temozolomide; Radiation: Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	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.	up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kaplan-Meier Plot of Progression Free Survival	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.	From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 6 years)
Overall Survival Rate 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.	At 24 Months
Overall Survival in Tumor Mutational Burden (TMB) High Population	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.	From randomization to the date of death due to any cause (up to approximately 6 years)
Progression Free Survival in Tumor Mutational Burden (TMB) High Population	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.	From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 6 years)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Ono Pharmaceutical Co. Ltd

Publications and helpful links

General 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.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): January 17, 2019
• Study Completion (Actual): March 4, 2022

Study Registration Dates

• First Submitted: November 26, 2015
• First Submitted That Met QC Criteria: November 26, 2015
• First Posted (Estimate): December 1, 2015

Study Record Updates

• Last Update Posted (Actual): March 28, 2023
• Last Update Submitted That Met QC Criteria: March 1, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Glioblastoma; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Temozolomide; Nivolumab
• Other Study ID Numbers: CA209-498; 2015-003739-37 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No