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)
2 other identifiers
interventional
560
18 countries
120
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2016
Longer than P75 for phase_3
120 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 26, 2015
CompletedFirst Posted
Study publicly available on registry
December 1, 2015
CompletedStudy Start
First participant enrolled
March 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 17, 2019
CompletedResults Posted
Study results publicly available
February 3, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
March 4, 2022
CompletedMarch 28, 2023
March 1, 2023
2.9 years
November 26, 2015
November 30, 2020
March 1, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (4)
Kaplan-Meier Plot of Progression Free Survival
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
At 24 Months
Overall Survival in Tumor Mutational Burden (TMB) High Population
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
From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 6 years)
Study Arms (2)
Nivolumab + Radiotherapy Arm
EXPERIMENTALNivolumab IV infusion + Radiotherapy dose as specified
Temozolomide + Radiotherapy Arm
ACTIVE COMPARATORTemozolomide + Radiotherapy dose as specified
Interventions
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bristol-Myers Squibblead
- Ono Pharmaceutical Co. Ltdcollaborator
Study Sites (125)
University of Alabama at Birmingham
Birmingham, Alabama, 35294-3410, United States
Local Institution - 0083
Phoenix, Arizona, 85013, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
Local Institution - 0019
Los Angeles, California, 90095-1769, United States
Sutter Institute For Medical Research
Sacramento, California, 95816, United States
Sharp Memorial Hospital
San Diego, California, 92123, United States
The Regents of the University of California, San Francisco
San Francisco, California, 94143-0372, United States
Yale Cancer Center
New Haven, Connecticut, 06520, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007, United States
University Of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 33136, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University - Winship Cancer Institute
Atlanta, Georgia, 30322, United States
The University Of Chicago
Chicago, Illinois, 60637, United States
University Of Kansas Medical Center
Westwood, Kansas, 66205, United States
Norton Cancer Institute
Louisville, Kentucky, 40202, United States
Johns Hopkins University School Of Medicine
Baltimore, Maryland, 21287, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Massachusetts General Hospital
Boston, Massachusetts, 02215, United States
Local Institution - 0006
Detroit, Michigan, 48202, United States
Washington University School OF Medicine-Siteman Cancer Center
St Louis, Missouri, 63110, United States
JFK Medical Center
Edison, New Jersey, 08820, United States
Local Institution - 0064
Hackensack, New Jersey, 07601, United States
Columbia University Medical Center (Cumc)
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Levine Cancer Institute
Charlotte, North Carolina, 28204, United States
Preston Robert Tisch Brain Tumor Center at Duke University
Durham, North Carolina, 27710, United States
Local Institution - 0010
Cleveland, Ohio, 44195, United States
Local Institution - 0095
Columbus, Ohio, 43210, United States
Local Institution - 0132
Allentown, Pennsylvania, 18103, United States
Local Institution - 0007
Philadelphia, Pennsylvania, 19107, United States
Medical University Of South Carolina
Charleston, South Carolina, 29425, United States
Local Institution - 0090
Chattanooga, Tennessee, 37404, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
University Of Texas Southwestern Medical Center
Dallas, Texas, 75390-8852, United States
University Of Texas Md Anderson Cancer Ctr
Houston, Texas, 77030, United States
Local Institution - 0068
Salt Lake City, Utah, 84112, United States
Swedish Neuroscience Institute
Seattle, Washington, 98122, United States
Royal North Shore Hospital
St Leonards, New South Wales, 2065, Australia
Local Institution - 0003
Heidelberg, Victoria, 3084, Australia
Local Institution - 0004
Prahran, Victoria, 3181, Australia
Local Institution - 0001
Nedlands, Western Australia, 6009, Australia
Local Institution - 0002
New South Wales, 2170, Australia
Local Institution - 0061
Linz, 4020, Austria
Local Institution - 0060
Vienna, 1090, Austria
Universitair Ziekenhuis Brussel
Brussels, 1090, Belgium
Cliniques Universitaires Saint-Luc
Brussels, 1200, Belgium
Uz Leuven
Leuven, 3000, Belgium
BC Cancer - Vancouver
Vancouver, British Columbia, V5Z 4E6, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9, Canada
Montreal Neurological Institute and Hospital
Montreal, Quebec, H3A 2B4, Canada
Local Institution
Copenhagen, 2100, Denmark
Local Institution
Odense, 5000, Denmark
Local Institution - 0032
Bron, 69677, France
Local Institution
Lille, 59037, France
Local Institution - 0024
Marseille, 13005, France
Local Institution - 0101
Nancy, 54035, France
Local Institution - 0023
Paris, 75010, France
Local Institution - 0038
Paris, 75651, France
Centre Eugene Marquis
Rennes, 35000, France
Local Institution - 0106
Toulouse, 31100, France
Local Institution - 0051
Bonn, 53105, Germany
Local Institution - 0139
Cologne, 50937, Germany
Local Institution - 0072
Erlangen, 91054, Germany
Local Institution - 0049
Frankfurt am Main, 60528, Germany
Local Institution - 0073
Freiburg im Breisgau, 79106, Germany
Local Institution - 0054
Hamburg, 20246, Germany
Local Institution - 0052
Heidelberg, 69120, Germany
Local Institution - 0138
Munich, 81675, Germany
Local Institution - 0050
Münster, 48149, Germany
Local Institution - 0055
Regensburg, 93053, Germany
Local Institution - 0056
Tübingen, 72076, Germany
Local Institution - 0096
Petah Tikva, 49100, Israel
Local Institution - 0097
Tel Aviv, 64239, Israel
Local Institution - 0076
Bologna, 40139, Italy
Local Institution - 0079
Milan, 20133, Italy
Local Institution - 0126
Padua, 35128, Italy
Local Institution - 0135
Rozzano (milano), 20089, Italy
Local Institution - 0078
Siena, 53100, Italy
Local Institution - 0077
Torino, 10126, Italy
Local Institution - 0115
Nagoya, Aichi-ken, 4668560, Japan
Local Institution - 0125
Chiba, Chiba, 2608677, Japan
Local Institution - 0123
Hiroshima, Hiroshima, 7348551, Japan
Local Institution - 0122
Sapporo, Hokkaido, 0608648, Japan
Local Institution - 0129
Kobe, Hyōgo, 6500017, Japan
Local Institution - 0111
Tsukuba, Ibaraki, 3058576, Japan
Local Institution - 0121
Kanazawa, Ishikawa-ken, 9200934, Japan
Local Institution - 0131
Kagoshima, Kagoshima-ken, 8908520, Japan
Local Institution - 0133
Sagamihara-shi, Kanagawa, 2520375, Japan
Local Institution - 0119
Kumamoto, Kumamoto, 8608556, Japan
Local Institution - 0117
Kyoto, Kyoto, 606-8507, Japan
Local Institution - 0116
Kyoto, Kyoto, 6128555, Japan
Local Institution - 0134
Okayama, Okayama-ken, 7008558, Japan
Local Institution
Hirakata-shi, Osaka, 5731191, Japan
Local Institution - 0130
Suita-shi, Osaka, 565-0871, Japan
Local Institution - 0113
Hidaka, Saitama, 350-1298, Japan
Local Institution - 0128
Bunkyo-ku, Tokyo, 1138655, Japan
Local Institution - 0114
Chuo-ku, Tokyo, 1040045, Japan
Local Institution - 0118
Mitaka-shi, Tokyo, 181-8611, Japan
Local Institution - 0110
Yamagata, Yamagata, 9909585, Japan
Local Institution - 0112
Tokyo, 1628666, Japan
NKI AVL
Amsterdam, 1066 CX, Netherlands
Universitair Medisch Centrum Groningen
Groningen, 9713 AP, Netherlands
Erasmus Mc
Rotterdam, 3015 CE, Netherlands
Local Institution - 0063
Utrecht, 3584CX, Netherlands
Local Institution
Oslo, 0379, Norway
Local Institution - 0080
Gdansk, 80952, Poland
Local Institution - 0081
Warsaw, 02-781, Poland
Local Institution - 0070
Moscow, 105229, Russia
Local Institution - 0105
Moscow, 115478, Russia
Local Institution
Badalona-Barcelona, 08916, Spain
Local Institution
Barcelona, 08035, Spain
Local Institution - 0028
Barcelona, 08036, Spain
Local Institution - 0029
Madrid, 28007, Spain
Local Institution
Madrid, 28041, Spain
Local Institution
Santiago de Compostela, 15706, Spain
Local Institution - 0025
Valencia, 46014, Spain
Local Institution
Lund, 221 85, Sweden
Local Institution
Solna, 171 64, Sweden
Local Institution - 0059
Geneva, 1211, Switzerland
Local Institution - 0057
Lausanne, 1011, Switzerland
Local Institution - 0053
Zurich, 8091, Switzerland
University College Hospital
London, Greater London, NW1 2PG, United Kingdom
Christie Hospital Nhs Found. Trust
Manchester, Greater Manchester, M20 4BX, United Kingdom
Royal Marsden Hospital
Sutton, Surrey, SM2 5PT, United Kingdom
Beaston West of Scotland Cancer Centre
Glasgow, G12 0YN, United Kingdom
Related Publications (3)
Grkovski M, Daras M, Bale T, Lyashchenko S, Reiner AS, Mellinghoff IK, Schoder H, Dunphy MPS. 18F-BMS-986229 PET imaging of tumor PD-L1 expression in glioblastoma patients. EJNMMI Res. 2025 Sep 26;15(1):124. doi: 10.1186/s13550-025-01283-x.
PMID: 41003913DERIVEDOmuro A, Brandes AA, Carpentier AF, Idbaih A, Reardon DA, Cloughesy T, Sumrall A, Baehring J, van den Bent M, Bahr O, Lombardi G, Mulholland P, Tabatabai G, Lassen U, Sepulveda JM, Khasraw M, Vauleon E, Muragaki Y, Di Giacomo AM, Butowski N, Roth P, Qian X, Fu AZ, Liu Y, Potter V, Chalamandaris AG, Tatsuoka K, Lim M, Weller M. Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial. Neuro Oncol. 2023 Jan 5;25(1):123-134. doi: 10.1093/neuonc/noac099.
PMID: 35419607DERIVEDWoroniecka 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.
PMID: 32691060DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Bristol-Myers Squibb Study Director
- Organization
- Bristol-Myers Squibb
Study Officials
- STUDY DIRECTOR
Bristol-Myers Squibb
Bristol-Myers Squibb
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
November 26, 2015
First Posted
December 1, 2015
Study Start
March 1, 2016
Primary Completion
January 17, 2019
Study Completion
March 4, 2022
Last Updated
March 28, 2023
Results First Posted
February 3, 2021
Record last verified: 2023-03