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)

NCT02667587 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CA209-5482015-004722-34
• Study Type: interventional
• Target: 716
• Locations: 18 countries
• Sites: 121

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.

Conditions

Brain Neoplasms

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS) Determined by BICR

  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.

  From randomization to the date of the first documented tumor progression or death by any cause. (up to approximately 4.5 years)

• Overall Survival (OS)

  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.

  From randomization to date of death (up to approximately 4.5 years)

Secondary Outcomes (3)

• Overall Survival (OS) Rates at 12 Months

  From randomization to 12 months after first dose

• Overall Survival (OS) Rates at 24 Months

  From randomization to 24 months after first dose

• Progression Free Survival (PFS) Based on Investigator Assessment

  From randomization to the date of the first documented tumor progression or death by any cause. (up to approximately 4.5 years)

Study Arms (2)

Nivolumab + Temozolomide + Radiotherapy

EXPERIMENTAL

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

Drug: Nivolumab; Drug: Temozolomide; Radiation: Radiotherapy

Nivolumab placebo + Temozolomide + Radiotherapy

PLACEBO COMPARATOR

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

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

Interventions

Nivolumab DRUG

Also known as: Opdivo, Nivo, N, BMS-936558

Nivolumab + Temozolomide + Radiotherapy

Temozolomide DRUG

Also known as: Temodar, TMZ, Temodal, Temcad

Nivolumab + Temozolomide + Radiotherapy; Nivolumab placebo + Temozolomide + Radiotherapy

Radiotherapy RADIATION

Also known as: RT

Nivolumab + Temozolomide + Radiotherapy; Nivolumab placebo + Temozolomide + Radiotherapy

Nivolumab Placebo OTHER

Nivolumab placebo + Temozolomide + Radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Ono Pharmaceutical Co. Ltd: collaborator

Study Sites (123)

Local Institution - 0023

Birmingham, Alabama, 35294-3410, United States

Location

Local Institution - 0003

Phoenix, Arizona, 85013, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Local Institution - 0010

Los Angeles, California, 90095-1769, United States

Location

Local Institution - 0128

Sacramento, California, 95816, United States

Location

Local Institution - 0029

San Diego, California, 92123, United States

Location

Local Institution - 0006

San Francisco, California, 94143-0372, United States

Location

Local Institution - 0004

New Haven, Connecticut, 06520, United States

Location

Local Institution - 0031

Washington D.C., District of Columbia, 20007, United States

Location

Local Institution - 0087

Miami, Florida, 33136, United States

Location

Local Institution - 0030

Tampa, Florida, 33612, United States

Location

Local Institution - 0022

Chicago, Illinois, 60637, United States

Location

Local Institution - 0060

Westwood, Kansas, 66205, United States

Location

Local Institution - 0018

Louisville, Kentucky, 40202, United States

Location

Local Institution - 0020

Baltimore, Maryland, 21287, United States

Location

Local Institution - 0011

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0028

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0035

Detroit, Michigan, 48202, United States

Location

Local Institution - 0002

St Louis, Missouri, 63110, United States

Location

Local Institution - 0017

Edison, New Jersey, 08820, United States

Location

Local Institution - 0012

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 0015

New York, New York, 10032, United States

Location

Local Institution - 0024

New York, New York, 10065, United States

Location

Local Institution - 0032

Charlotte, North Carolina, 28204, United States

Location

Preston Robert Tisch Brain Tumor Center at Duke University

Durham, North Carolina, 27710, United States

Location

Local Institution - 0001

Cleveland, Ohio, 44195, United States

Location

Local Institution - 0027

Columbus, Ohio, 43210, United States

Location

Local Institution - 0098

Allentown, Pennsylvania, 18103, United States

Location

Local Institution - 0016

Philadelphia, Pennsylvania, 19107, United States

Location

Local Institution - 0021

Charleston, South Carolina, 29425, United States

Location

Erlanger Oncology & Hematology - Univ. of TN

Chattanooga, Tennessee, 37403, United States

Location

Local Institution - 0008

Nashville, Tennessee, 37232, United States

Location

Local Institution - 0025

Dallas, Texas, 75390-8575, United States

Location

Local Institution - 0009

Salt Lake City, Utah, 84112, United States

Location

Local Institution - 0005

Seattle, Washington, 98122, United States

Location

Local Institution - 0049

Liverpool, New South Wales, 2170, Australia

Location

Local Institution - 0052

St Leonards, New South Wales, 2065, Australia

Location

Local Institution - 0050

Heidelberg, Victoria, 3084, Australia

Location

Local Institution - 0051

Prahran, Victoria, 3181, Australia

Location

Local Institution - 0122

Nedlands, Western Australia, 6009, Australia

Location

Local Institution - 0062

Linz, 4020, Austria

Location

Local Institution - 0061

Vienna, 1090, Austria

Location

Local Institution - 0070

Brussels, 1090, Belgium

Location

Local Institution - 0069

Brussels, 1200, Belgium

Location

Local Institution - 0071

Leuven, 3000, Belgium

Location

Local Institution - 0046

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Local Institution - 0048

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 0047

Montreal, Quebec, H3A 2B4, Canada

Location

Local Institution - 0084

Copenhagen, 2100, Denmark

Location

Local Institution - 0085

Odense, 5000, Denmark

Location

Local Institution - 0043

Lille, 59037, France

Location

Local Institution - 0041

Lyon, 69394, France

Location

Local Institution - 0040

Marseille, 13385, France

Location

Local Institution - 0042

Nancy, 54035, France

Location

Local Institution - 0038

Paris, 75010, France

Location

Local Institution - 0039

Paris, 75651, France

Location

Local Institution - 0044

Rennes, 35042, France

Location

Local Institution - 0045

Toulouse, 31100, France

Location

Local Institution - 0055

Bonn, 53127, Germany

Location

Local Institution - 0131

Cologne, 50937, Germany

Location

Local Institution - 0123

Erlangen, 91054, Germany

Location

Local Institution - 0053

Frankfurt am Main, 60528, Germany

Location

Local Institution - 0124

Freiburg im Breisgau, 79106, Germany

Location

Local Institution - 0057

Hamburg, 20246, Germany

Location

Local Institution - 0056

Heidelberg, 69120, Germany

Location

Local Institution - 0130

Munich, 81675, Germany

Location

Local Institution - 0054

Münster, 48149, Germany

Location

Local Institution - 0058

Regensburg, 93053, Germany

Location

Local Institution - 0059

Tübingen, 72076, Germany

Location

Local Institution - 0094

Petah Tikva, 49100, Israel

Location

Local Institution - 0093

Tel Aviv, 64239, Israel

Location

Local Institution - 0088

Bologna, 40139, Italy

Location

Local Institution - 0089

Milan, 20133, Italy

Location

Local Institution - 0092

Padua, 35128, Italy

Location

Local Institution - 0127

Rozzano (milano), 20089, Italy

Location

Local Institution - 0090

Siena, 53100, Italy

Location

Local Institution - 0091

Torino, 10126, Italy

Location

Local Institution - 0110

Nagoya, Aichi-ken, 4668560, Japan

Location

Local Institution - 0099

Chiba, Chiba, 2608677, Japan

Location

Local Institution - 0100

Hiroshima, Hiroshima, 7348551, Japan

Location

Local Institution - 0101

Sapporo, Hokkaido, 0608648, Japan

Location

Local Institution - 0105

Kobe, Hyōgo, 650-0017, Japan

Location

Local Institution - 0116

Tsukuba, Ibaraki, 3058576, Japan

Location

Local Institution - 0103

Kanazawa, Ishikawa-ken, 9200934, Japan

Location

Local Institution - 0102

Kagoshima, Kagoshima-ken, 8908520, Japan

Location

Local Institution - 0118

Sagamihara-shi, Kanagawa, 2520375, Japan

Location

Local Institution - 0106

Kumamoto, Kumamoto, 8608556, Japan

Location

Local Institution - 0120

Okayama, Okayama-ken, 7008558, Japan

Location

Local Institution - 0104

Hirakata-shi, Osaka, 5731191, Japan

Location

Local Institution - 0112

Suita, Osaka, 5650871, Japan

Location

Local Institution - 0121

Hidaka-shi, Saitama, 3501298, Japan

Location

Local Institution - 0114

Bunkyo-ku, Tokyo, 1138655, Japan

Location

Local Institution - 0111

Chuo-ku, Tokyo, 1040045, Japan

Location

Local Institution - 0107

Mitaka-shi, Tokyo, 181-8611, Japan

Location

Local Institution - 0115

Shinjuku-ku, Tokyo, 1628666, Japan

Location

Local Institution - 0117

Yamagata, Yamagata, 9909585, Japan

Location

Local Institution - 0109

Kyoto, 6068507, Japan

Location

Local Institution - 0108

Kyoto, 612-8555, Japan

Location

Local Institution - 0073

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Local Institution - 0075

Amsterdam, 1066 CX, Netherlands

Location

Local Institution - 0074

Groningen, 9713 AP, Netherlands

Location

Local Institution - 0072

Utrecht, 3584 CX, Netherlands

Location

Local Institution - 0083

Oslo, 0424, Norway

Location

Local Institution - 0086

Gdansk, 80-214, Poland

Location

Local Institution - 0132

Warsaw, 02-781, Poland

Location

Local Institution - 0095

Moscow, 105229, Russia

Location

Local Institution - 0097

Moscow, 115478, Russia

Location

Local Institution - 0126

Badalona-barcelona, 08916, Spain

Location

Local Institution - 0078

Barcelona, 08035, Spain

Location

Local Institution - 0125

Barcelona, 08036, Spain

Location

Local Institution - 0077

Madrid, 28009, Spain

Location

Local Institution - 0076

Madrid, 28041, Spain

Location

Local Institution - 0080

Santiago Compostela, 15706, Spain

Location

Local Institution - 0079

Valencia, 46014, Spain

Location

Local Institution - 0081

Lund, 221 85, Sweden

Location

Local Institution - 0082

Solna, 171 64, Sweden

Location

Local Institution - 0065

Geneva, 1211, Switzerland

Location

Local Institution - 0064

Lausanne, 1011, Switzerland

Location

Local Institution - 0063

Zurich, 8091, Switzerland

Location

Local Institution - 0066

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Local Institution - 0119

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Local Institution - 0068

Glasgow, G12 0YN, United Kingdom

Location

Local Institution - 0067

London, NW1 2BU, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 35511454 DERIVED

• 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.

  PMID: 32691060 DERIVED

Related Links

• BMS Clinical Trial Information
• FDA Safety Alerts and Recalls
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Nivolumab; Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: January 26, 2016
• First Posted: January 29, 2016
• Study Start: May 9, 2016
• Primary Completion: December 22, 2020
• Study Completion: April 9, 2024
• Last Updated: June 18, 2025
• Results First Posted: February 3, 2022

Record last verified: 2025-06

Locations

BE (3); IT (6); JP (21); RU (2); CA (3); DE (11); ES (7); SE (2); PL (2); NO (1); CH (3); DK (2); GB (4); NL (4); AU (5); FR (8); US (35); IL (2)