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Brain CancerPhase 3CheckMate 498NCT02617589

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)

A Phase 3 study testing Nivolumab, Temozolomide and Radiotherapy in people with Brain Cancer, run by Bristol-Myers Squibb at 125 sites in 19 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Brain Cancer
What is being tested?
Nivolumab, Temozolomide and Radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
560 participants
Where
125 sitesin 19 countries
Study dates
1 Mar 2016to 4 Mar 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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

Trial locations and contacts

125 sites in 19 countries.

125 sites in 19 countries

United States37 sites

  • Local Institution - 0132

    Allentown, Pennsylvania, 18103

  • Emory University - Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Johns Hopkins University School Of Medicine

    Baltimore, Maryland, 21287

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294-3410

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Massachusetts General Hospital

    Boston, Massachusetts, 02215

  • Medical University Of South Carolina

    Charleston, South Carolina, 29425

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • Local Institution - 0090

    Chattanooga, Tennessee, 37404

  • The University Of Chicago

    Chicago, Illinois, 60637

  • Local Institution - 0010

    Cleveland, Ohio, 44195

  • Local Institution - 0095

    Columbus, Ohio, 43210

  • University Of Texas Southwestern Medical Center

    Dallas, Texas, 75390-8852

  • Local Institution - 0006

    Detroit, Michigan, 48202

  • Preston Robert Tisch Brain Tumor Center at Duke University

    Durham, North Carolina, 27710

  • JFK Medical Center

    Edison, New Jersey, 08820

  • Local Institution - 0064

    Hackensack, New Jersey, 07601

  • University Of Texas Md Anderson Cancer Ctr

    Houston, Texas, 77030

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Local Institution - 0019

    Los Angeles, California, 90095-1769

  • Norton Cancer Institute

    Louisville, Kentucky, 40202

  • University Of Miami Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Yale Cancer Center

    New Haven, Connecticut, 06520

  • Columbia University Medical Center (Cumc)

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Local Institution - 0007

    Philadelphia, Pennsylvania, 19107

  • Local Institution - 0083

    Phoenix, Arizona, 85013

  • Sutter Institute For Medical Research

    Sacramento, California, 95816

  • Local Institution - 0068

    Salt Lake City, Utah, 84112

  • Sharp Memorial Hospital

    San Diego, California, 92123

  • The Regents of the University of California, San Francisco

    San Francisco, California, 94143-0372

  • Swedish Neuroscience Institute

    Seattle, Washington, 98122

  • Washington University School OF Medicine-Siteman Cancer Center

    St Louis, Missouri, 63110

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

  • University Of Kansas Medical Center

    Westwood, Kansas, 66205

Other trials in United States

Japan21 sites

  • Local Institution - 0128

    Bunkyo-ku, Tokyo, 1138655

  • Local Institution - 0125

    Chiba, Chiba, 2608677

  • Local Institution - 0114

    Chuo-ku, Tokyo, 1040045

  • Local Institution - 0113

    Hidaka, Saitama, 350-1298

  • Local Institution

    Hirakata-shi, Osaka, 5731191

  • Local Institution - 0123

    Hiroshima, Hiroshima, 7348551

  • Local Institution - 0131

    Kagoshima, Kagoshima-ken, 8908520

  • Local Institution - 0121

    Kanazawa, Ishikawa-ken, 9200934

  • Local Institution - 0129

    Kobe, Hyōgo, 6500017

  • Local Institution - 0119

    Kumamoto, Kumamoto, 8608556

  • Local Institution - 0117

    Kyoto, Kyoto, 606-8507

  • Local Institution - 0116

    Kyoto, Kyoto, 6128555

  • Local Institution - 0118

    Mitaka-shi, Tokyo, 181-8611

  • Local Institution - 0115

    Nagoya, Aichi-ken, 4668560

  • Local Institution - 0134

    Okayama, Okayama-ken, 7008558

  • Local Institution - 0133

    Sagamihara-shi, Kanagawa, 2520375

  • Local Institution - 0122

    Sapporo, Hokkaido, 0608648

  • Local Institution - 0130

    Suita-shi, Osaka, 565-0871

  • Local Institution - 0112

    Tokyo, 1628666

  • Local Institution - 0111

    Tsukuba, Ibaraki, 3058576

  • Local Institution - 0110

    Yamagata, Yamagata, 9909585

Other trials in Japan

Germany11 sites

  • Local Institution - 0051

    Bonn, 53105

  • Local Institution - 0139

    Cologne, 50937

  • Local Institution - 0072

    Erlangen, 91054

  • Local Institution - 0049

    Frankfurt am Main, 60528

  • Local Institution - 0073

    Freiburg im Breisgau, 79106

  • Local Institution - 0054

    Hamburg, 20246

  • Local Institution - 0052

    Heidelberg, 69120

  • Local Institution - 0138

    Munich, 81675

  • Local Institution - 0050

    Münster, 48149

  • Local Institution - 0055

    Regensburg, 93053

  • Local Institution - 0056

    Tübingen, 72076

Other trials in Germany

France8 sites

  • Local Institution - 0032

    Bron, 69677

  • Local Institution

    Lille, 59037

  • Local Institution - 0024

    Marseille, 13005

  • Local Institution - 0101

    Nancy, 54035

  • Local Institution - 0023

    Paris, 75010

  • Local Institution - 0038

    Paris, 75651

  • Centre Eugene Marquis

    Rennes, 35000

  • Local Institution - 0106

    Toulouse, 31100

Other trials in France

Spain7 sites

  • Local Institution

    Badalona-Barcelona, 08916

  • Local Institution

    Barcelona, 08035

  • Local Institution - 0028

    Barcelona, 08036

  • Local Institution - 0029

    Madrid, 28007

  • Local Institution

    Madrid, 28041

  • Local Institution

    Santiago de Compostela, 15706

  • Local Institution - 0025

    Valencia, 46014

Other trials in Spain

Italy6 sites

  • Local Institution - 0076

    Bologna, 40139

  • Local Institution - 0079

    Milan, 20133

  • Local Institution - 0126

    Padova, 35128

  • Local Institution - 0135

    Rozzano (milano), 20089

  • Local Institution - 0078

    Siena, 53100

  • Local Institution - 0077

    Torino, 10126

Other trials in Italy

Australia5 sites

  • Local Institution - 0003

    Heidelberg, Victoria, 3084

  • Local Institution - 0001

    Nedlands, Western Australia, 6009

  • Local Institution - 0002

    New South Wales, 2170

  • Local Institution - 0004

    Prahran, Victoria, 3181

  • Royal North Shore Hospital

    St Leonards, New South Wales, 2065

Other trials in Australia

Netherlands4 sites

  • NKI AVL

    Amsterdam, 1066 CX

  • Universitair Medisch Centrum Groningen

    Groningen, 9713 AP

  • Erasmus Mc

    Rotterdam, 3015 CE

  • Local Institution - 0063

    Utrecht, 3584CX

Other trials in Netherlands

United Kingdom4 sites

  • Beaston West of Scotland Cancer Centre

    Glasgow, G12 0YN

  • University College Hospital

    London, Greater London, NW1 2PG

  • Christie Hospital Nhs Found. Trust

    Manchester, Greater Manchester, M20 4BX

  • Royal Marsden Hospital

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

Belgium3 sites

  • Universitair Ziekenhuis Brussel

    Brussels, 1090

  • Cliniques Universitaires Saint-Luc

    Brussels, 1200

  • Uz Leuven

    Leuven, 3000

Other trials in Belgium

Canada3 sites

  • Montreal Neurological Institute and Hospital

    Montreal, Quebec, H3A 2B4

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

  • BC Cancer - Vancouver

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

Switzerland3 sites

  • Local Institution - 0059

    Geneva, 1211

  • Local Institution - 0057

    Lausanne, 1011

  • Local Institution - 0053

    Zurich, 8091

Other trials in Switzerland

Austria2 sites

  • Local Institution - 0061

    Linz, 4020

  • Local Institution - 0060

    Vienna, 1090

Other trials in Austria

Denmark2 sites

  • Local Institution

    Copenhagen, 2100

  • Local Institution

    Odense, 5000

Other trials in Denmark

Israel2 sites

  • Local Institution - 0096

    Petah Tikva, 49100

  • Local Institution - 0097

    Tel Aviv, 64239

Other trials in Israel

Poland2 sites

  • Local Institution - 0080

    Gdansk, 80952

  • Local Institution - 0081

    Warsaw, 02-781

Other trials in Poland

Russia2 sites

  • Local Institution - 0070

    Moscow, 105229

  • Local Institution - 0105

    Moscow, 115478

Other trials in Russia

Sweden2 sites

  • Local Institution

    Lund, 221 85

  • Local Institution

    Solna, 171 64

Other trials in Sweden

Norway1 site

  • Local Institution

    Oslo, 0379

Other trials in Norway

About this study

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)

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.

Conditions
Brain Cancer
Being tested
Nivolumab, Temozolomide, Radiotherapy
Medical subject headings
Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02617589
Study groupRoleWhat they receive
Nivolumab + Radiotherapy ArmExperimentalNivolumab IV infusion + Radiotherapy dose as specified
Receives: Drug: Nivolumab; Radiation: Radiotherapy
Temozolomide + Radiotherapy ArmActive comparatorTemozolomide + Radiotherapy dose as specified
Receives: Drug: Temozolomide; Radiation: Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: up to 3 years

Secondary outcomes (4)

  1. 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.

    Measured: From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 6 years)

  2. 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.

    Measured: At 24 Months

  3. 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.

    Measured: From randomization to the date of death due to any cause (up to approximately 6 years)

  4. 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.

    Measured: From randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 6 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Dec 2015 (estimated)
  2. Study start1 Mar 2016
  3. Primary completion17 Jan 2019
  4. Study completion4 Mar 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
560 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02617589
Sponsor's protocol ID
CA209-498
Other IDs
2015-003739-37, 2015
Acronym
CheckMate 498
Status last verified
Mar 2023
First submitted
26 Nov 2015
Last updated
28 Mar 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Expanded access
Available

Publications

  • 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.

    PubMed 41003913

  • Omuro 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.

    PubMed 35419607

  • 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.

    PubMed 32691060

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nivolumab, Temozolomide and Radiotherapy in people with Brain Cancer, run by Bristol-Myers Squibb at 125 sites in 19 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 125 sites in United States, Japan, Germany, France, Spain and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) (time frame: up to 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02617589, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2023.

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