A Study of the Effectiveness and Safety of Nivolumab Compared to Bevacizumab and of Nivolumab With or Without Ipilimumab in Glioblastoma Patients

NCT02017717 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CA209-1432013-003738-34
• Study Type: interventional
• Target: 529
• Locations: 12 countries
• Sites: 112

Brief Summary

The purpose of the study is to compare the efficacy and safety of nivolumab administered alone versus bevacizumab in patients diagnosed with recurrent glioblastoma (a type of brain cancer, also known as GBM), and to evaluate the safety and tolerability of nivolumab administered alone or in combination with ipilimumab in patients with different lines of GBM therapy.

Conditions

Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (6)

• Percentage of Participants With Drug-Related Adverse Events Leading to Discontinuation by Worst CTC Grade for All Treated Participants in Cohorts 1, 1b, 1c and 1d Who Permanently Discontinued Study Medication Prior to Completing Four Doses

  The percentage of participants who experienced a drug-related adverse event leading to drug discontinuation by worst grade (grade 5 being the worst) prior to complete four-dose treatment. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. MedDRA Version: 24.1

  Includes events reported between first dose and 30 days after last dose of study therapy (up to 3 doses, up to approximately 2 months)

• Percentage of Participants With Adverse Events (Worst Grade) in Cohorts 1, 1b, 1c and 1d

  The percentage of participants who experienced an adverse event by worst grade in each treatment arm. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. MedDRA Version: 24.1

  From first dose to 30 days post last dose (up to approximately 34 months).

• Percentage of Participants With Serious Adverse Events (Worst Grade) in Cohorts 1, 1b, 1c and 1d

  The percentage of participants who experienced a serious adverse event by worst grade in each treatment arm. Toxicities were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. MedDRA Version: 24.1

  From first dose to 30 days post last dose (up to approximately 34 months).

• Percentage of Participants With Specific Laboratory Abnormalities in Liver Tests in Cohorts 1, 1b, 1c and 1d

  The percentage of participants who experienced a laboratory abnormality of the liver in each treatment arm. MedDRA Version: 24.1 Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN) Denominator corresponds to participants with at least on one treatment measurement of the corresponding laboratory parameter. Includes laboratory results reported after the first dose and within 30 days of last dose of study therapy.

  From first dose to 30 days post last dose (up to approximately 34 months).

• Percentage of Participants With Specific Laboratory Abnormalities in Thyroid Tests in Cohorts 1, 1b, 1c and 1d

  The percentage of participants who experienced a laboratory abnormality of the thyroid in each treatment arm. MedDRA Version: 24.1 Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN) (A) Within a 2-week window after the abnormal TSH test date. (B) Includes participants with TSH abnormality and with no FT3/FT4 test values in the 2-week window or with non-abnormal value(s) from only one of the two tests and no value from the other test.

  From first dose to 30 days post last dose (up to approximately 34 months).

• Overall Survival (OS) for Cohort 2

  OS was measured in months from the time of randomization to the event date (death) due to any cause. A participant who has not died will be censored at the last known alive date. Based on Kaplan-Meier Estimates. Hazard ratio from Cox proportional hazard model stratified by presence of measurable lesions at baseline per IVRS. P-value from log-rank test stratified by presence of measurable lesions at baseline per IVRS.

  Time between the date of randomization and the date of death due to any cause (up to up to 17Jun2019, approximately 5 years)

Secondary Outcomes (4)

• Overall Survival (OS) at 12 Months for Cohort 2

  From randomization to 12 months following randomization

• Overall Survival (OS) for Cohorts 1c and 1d

  Time between the date of randomization and the date of death due to any cause (up to approximately 10 years and 5 months)

• Progression Free Survival (PFS) for Cohort 2

  Time from randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 10 years and 5 months)

• Objective Response Rate (ORR) for Cohort 2

  Time from randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 10 years and 5 months)

Study Arms (3)

Arm N:Nivolumab

EXPERIMENTAL

Cohort 1, 1c, 1d and 2: Nivolumab specified dose on specified days

Biological: Nivolumab

Arm N + I:Nivolumab + Ipilimumab

EXPERIMENTAL

Cohort 1: Nivolumab specified dose on specified days + Ipilimumab specified dose on specified days, then Nivolumab specified dose on specified days Cohort 1b: Nivolumab specified dose on specified days + Ipilimumab specified dose on specified days, then Nivolumab specified dose on specified days

Biological: Nivolumab; Biological: Ipilimumab

Arm B: Bevacizumab

ACTIVE COMPARATOR

Cohort 2: Bevacizumab specified dose on specified days

Biological: Bevacizumab

Interventions

Nivolumab BIOLOGICAL

specified dose on specified days

Also known as: BMS-936558

Arm N + I:Nivolumab + Ipilimumab; Arm N:Nivolumab

Bevacizumab BIOLOGICAL

specified dose on specified days

Also known as: Avastin

Arm B: Bevacizumab

Ipilimumab BIOLOGICAL

specified dose on specified days

Also known as: Yervoy

Arm N + I:Nivolumab + Ipilimumab

Eligibility Criteria

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

You may qualify if:

• Participants with histologically confirmed Grade IV malignant glioma
• Previous treatment with radiotherapy and temozolomide (Cohorts 1, 1b and 2 only)
• First recurrence of GBM (Cohorts 1, 1b and 2 only)
• First diagnosis of GBM with resectable disease (Cohorts 1c Part A only)
• First diagnosis of unmethylated MGMT GBM (Cohort 1d and Cohort 1c Part B only)
• Karnofsky performance score of 70 or higher

You may not qualify if:

• More than 1 recurrence of GBM (Cohorts 1, 1b and 2 only)
• Any recurrence of GBM (Cohorts 1c and 1d only)
• Presence of extracranial metastatic or leptomeningeal disease
• Active, known or suspected autoimmune disease
• Clinically significant cardiovascular disease
• Prior bevacizumab or other Vascular Endothelial Growth Factor (VEGF) or anti-angiogenic treatment (Cohort 2 only)

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (112)

University of Alabama at Birmingham

Birmingham, Alabama, 35294-3410, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Local Institution - 0055

Los Angeles, California, 90048, United States

Location

Local Institution - 0009

Los Angeles, California, 90095-1769, United States

Location

UCLA Neuro-Oncology Program

Los Angeles, California, 90095-1769, United States

Location

Local Institution - 0014

San Francisco, California, 94143-0372, United States

Location

The Regents of the University of California, San Francisco

San Francisco, California, 94143-0372, United States

Location

Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Local Institution - 0021

Aurora, Colorado, 80045, United States

Location

Local Institution - 0001

New Haven, Connecticut, 06520, United States

Location

Yale University School Of Medicine

New Haven, Connecticut, 06520, United States

Location

Georgetown University

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

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Local Institution - 0002

Atlanta, Georgia, 30322, United States

Location

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins University School Of Medicine

Baltimore, Maryland, 21287, United States

Location

Local Institution - 0008

Baltimore, Maryland, 21287, United States

Location

Beth Israel Deaconess Med Ctr

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0006

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0043

Boston, Massachusetts, 02215, United States

Location

Local Institution - 0056

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202-2608, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Local Institution - 0003

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Local Institution - 0007

Durham, North Carolina, 27710, United States

Location

Preston Robert Tisch Brain Tumor Center at Duke University

Durham, North Carolina, 27710, United States

Location

Local Institution - 0049

Cleveland, Ohio, 44106, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Thomas Jefferson University - Clinical Research Institute

Philadelphia, Pennsylvania, 19107, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Local Institution - 0023

Charleston, South Carolina, 29425, United States

Location

Medical University Of South Carolina

Charleston, South Carolina, 29425, United States

Location

Local Institution - 0005

Nashville, Tennessee, 37232, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Local Institution - 0024

Houston, Texas, 77030-4009, United States

Location

University Of Texas Md Anderson Cancer Ctr

Houston, Texas, 77030-4009, United States

Location

University Of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Local Institution - 0020

Seattle, Washington, 98122, United States

Location

Swedish Neuroscience Institute

Seattle, Washington, 98122, United States

Location

Local Institution - 0035

Liverpool, New South Wales, 2170, Australia

Location

Local Institution

Liverpool, New South Wales, 2170, Australia

Location

Local Institution - 0034

East Bentleigh, Victoria, 3165, Australia

Location

Local Institution

East Bentleigh, Victoria, 3165, Australia

Location

Local Institution - 0033

Heidelberg, Victoria, 3084, Australia

Location

Local Institution

Heidelberg, Victoria, 3084, Australia

Location

Local Institution - 0032

Nedlands, Western Australia, 6009, Australia

Location

Local Institution

Nedlands, Western Australia, 6009, Australia

Location

Local Institution - 0050

Brussels, 1090, Belgium

Location

Local Institution

Brussels, 1090, Belgium

Location

Local Institution - 0051

Brussels, 1200, Belgium

Location

Local Institution

Brussels, 1200, Belgium

Location

Aarhus University Hospital

Aarhus C, 8000, Denmark

Location

Local Institution - 0058

Aarhus C, 8000, Denmark

Location

Local Institution - 0057

Odense C, 5000, Denmark

Location

Odense University Hospital

Odense C, 5000, Denmark

Location

Local Institution - 0062

Bron, 69677, France

Location

Local Institution

Bron, 69677, France

Location

Local Institution - 0063

Marseille, 13385, France

Location

Local Institution

Marseille, 13385, France

Location

Local Institution - 0068

Paris, 75010, France

Location

Local Institution

Paris, 75010, France

Location

Local Institution - 0064

Paris, 75651, France

Location

Local Institution

Paris, 75651, France

Location

Local Institution - 0037

Bonn, 53127, Germany

Location

Universitaetsklinikum Bonn

Bonn, 53127, Germany

Location

Klinikum Der J. W. Goethe-Universitaet Frankfurt/Main

Frankfurt am Main, 60528, Germany

Location

Local Institution - 0036

Frankfurt am Main, 60528, Germany

Location

Local Institution - 0038

Heidelberg, 69120, Germany

Location

Local Institution

Heidelberg, 69120, Germany

Location

Local Institution - 0041

Münster, 48149, Germany

Location

Universitaetsklinikum Muenster

Münster, 48149, Germany

Location

Local Institution - 0010

Bologna, 40139, Italy

Location

Local Institution

Bologna, 40139, Italy

Location

Local Institution - 0011

Milan, 20133, Italy

Location

Local Institution

Milan, 20133, Italy

Location

Local Institution - 0012

Siena, 53100, Italy

Location

Local Institution

Siena, 53100, Italy

Location

Azienda Ospedaliera Citta della Salute e della Scienza

Torino, 10126, Italy

Location

Local Institution - 0013

Torino, 10126, Italy

Location

Local Institution - 0067

Amsterdam, 1066CX, Netherlands

Location

Local Institution

Amsterdam, 1066CX, Netherlands

Location

Local Institution - 0066

Groningen, 9713 AP, Netherlands

Location

Local Institution

Groningen, 9713 AP, Netherlands

Location

Local Institution - 0060

Gdansk, 80-952, Poland

Location

Local Institution

Gdansk, 80-952, Poland

Location

Local Institution - 0059

Warsaw, 02-781, Poland

Location

Local Institution

Warsaw, 02-781, Poland

Location

Local Institution - 0047

Barcelona, 08035, Spain

Location

Local Institution

Barcelona, 08035, Spain

Location

Local Institution - 0045

Madrid, 28009, Spain

Location

Local Institution

Madrid, 28009, Spain

Location

Local Institution - 0046

Madrid, 28041, Spain

Location

Local Institution

Madrid, 28041, Spain

Location

Local Institution - 0070

Pamplona, 31008, Spain

Location

Local Institution

Pamplona, 31008, Spain

Location

Centre hospitalier universitaire Vaudois (CHUV)

Lausanne, BT 02252, Switzerland

Location

Local Institution - 0039

Lausanne, BT 02252, Switzerland

Location

Local Institution - 0040

Zurich, 8091, Switzerland

Location

UniversitaetsSpital Zurich

Zurich, 8091, Switzerland

Location

Local Institution - 0018

London, Greater London, NW1 2PG, United Kingdom

Location

Local Institution

London, Greater London, NW1 2PG, United Kingdom

Location

Local Institution - 0015

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Local Institution

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Local Institution - 0017

Liverpool, L7 8YA, United Kingdom

Location

Local Institution

Liverpool, L7 8YA, United Kingdom

Location

Related Publications (4)

• de Melo SM, Elias Nunes da Silva ME, Torloni MR, Riera R, De Cicco K, Latorraca CO, Pinto ACPN. Anti-PD-1 and anti-PD-L1 antibodies for glioma. Cochrane Database Syst Rev. 2025 Jan 8;1(1):CD012532. doi: 10.1002/14651858.CD012532.pub2.

  PMID: 39777725 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

• Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M, Wick A, Baehring J, Ahluwalia MS, Roth P, Bahr O, Phuphanich S, Sepulveda JM, De Souza P, Sahebjam S, Carleton M, Tatsuoka K, Taitt C, Zwirtes R, Sampson J, Weller M. Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Jul 1;6(7):1003-1010. doi: 10.1001/jamaoncol.2020.1024.

  PMID: 32437507 DERIVED

• Stupp R. Drug development for glioma: are we repeating the same mistakes? Lancet Oncol. 2019 Jan;20(1):10-12. doi: 10.1016/S1470-2045(18)30827-1. Epub 2018 Dec 3. No abstract available.

  PMID: 30522968 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Glioblastoma

Interventions

Nivolumab; Bevacizumab; Ipilimumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2013
• First Posted: December 23, 2013
• Study Start: February 7, 2014
• Primary Completion: June 17, 2019
• Study Completion: June 21, 2024
• Last Updated: April 4, 2025
• Results First Posted: June 29, 2022

Record last verified: 2025-03

Locations

CH (4); PL (4); ES (8); IT (8); GB (6); DE (8); DK (4); BE (4); US (46); AU (8); FR (8); NL (4)