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)

NCT ID: NCT02667587

Last Updated: 2025-06-18

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

716 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-09

Study Completion Date

2024-04-09

Brief Summary

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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.

Detailed Description

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Conditions

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Brain Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Nivolumab + Temozolomide + Radiotherapy

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type DRUG

Temozolomide

Intervention Type DRUG

Radiotherapy

Intervention Type RADIATION

Nivolumab placebo + Temozolomide + Radiotherapy

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

Group Type PLACEBO_COMPARATOR

Temozolomide

Intervention Type DRUG

Radiotherapy

Intervention Type RADIATION

Nivolumab Placebo

Intervention Type OTHER

Interventions

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Nivolumab

Intervention Type DRUG

Temozolomide

Intervention Type DRUG

Radiotherapy

Intervention Type RADIATION

Nivolumab Placebo

Intervention Type OTHER

Other Intervention Names

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Opdivo Nivo N BMS-936558 Temodar TMZ Temodal Temcad RT

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ono Pharmaceutical Co. Ltd

INDUSTRY

Sponsor Role collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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Local Institution - 0023

Birmingham, Alabama, United States

Site Status

Local Institution - 0003

Phoenix, Arizona, United States

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Cedars Sinai Medical Center

Los Angeles, California, United States

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Local Institution - 0010

Los Angeles, California, United States

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Local Institution - 0128

Sacramento, California, United States

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Local Institution - 0029

San Diego, California, United States

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Local Institution - 0006

San Francisco, California, United States

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Local Institution - 0004

New Haven, Connecticut, United States

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Local Institution - 0031

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

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Local Institution - 0087

Miami, Florida, United States

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Local Institution - 0030

Tampa, Florida, United States

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Local Institution - 0022

Chicago, Illinois, United States

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Local Institution - 0060

Westwood, Kansas, United States

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Local Institution - 0018

Louisville, Kentucky, United States

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Local Institution - 0020

Baltimore, Maryland, United States

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Local Institution - 0011

Boston, Massachusetts, United States

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Local Institution - 0028

Boston, Massachusetts, United States

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Local Institution - 0035

Detroit, Michigan, United States

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Local Institution - 0002

St Louis, Missouri, United States

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Local Institution - 0017

Edison, New Jersey, United States

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Local Institution - 0012

Hackensack, New Jersey, United States

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Local Institution - 0015

New York, New York, United States

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Local Institution - 0024

New York, New York, United States

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Local Institution - 0032

Charlotte, North Carolina, United States

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Preston Robert Tisch Brain Tumor Center at Duke University

Durham, North Carolina, United States

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Local Institution - 0001

Cleveland, Ohio, United States

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Local Institution - 0027

Columbus, Ohio, United States

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Local Institution - 0098

Allentown, Pennsylvania, United States

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Local Institution - 0016

Philadelphia, Pennsylvania, United States

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Local Institution - 0021

Charleston, South Carolina, United States

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Erlanger Oncology & Hematology - Univ. of TN

Chattanooga, Tennessee, United States

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Local Institution - 0008

Nashville, Tennessee, United States

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Local Institution - 0025

Dallas, Texas, United States

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Local Institution - 0009

Salt Lake City, Utah, United States

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Local Institution - 0005

Seattle, Washington, United States

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Local Institution - 0049

Liverpool, New South Wales, Australia

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Local Institution - 0052

St Leonards, New South Wales, Australia

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Local Institution - 0050

Heidelberg, Victoria, Australia

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Local Institution - 0051

Prahran, Victoria, Australia

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Local Institution - 0122

Nedlands, Western Australia, Australia

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Local Institution - 0062

Linz, , Austria

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Local Institution - 0061

Vienna, , Austria

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Local Institution - 0070

Brussels, , Belgium

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Local Institution - 0069

Brussels, , Belgium

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Local Institution - 0071

Leuven, , Belgium

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Local Institution - 0046

Vancouver, British Columbia, Canada

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Local Institution - 0048

Toronto, Ontario, Canada

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Local Institution - 0047

Montreal, Quebec, Canada

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Local Institution - 0084

Copenhagen, , Denmark

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Local Institution - 0085

Odense, , Denmark

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Local Institution - 0043

Lille, , France

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Local Institution - 0041

Lyon, , France

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Local Institution - 0040

Marseille, , France

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Local Institution - 0042

Nancy, , France

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Local Institution - 0038

Paris, , France

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Local Institution - 0039

Paris, , France

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Local Institution - 0044

Rennes, , France

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Local Institution - 0045

Toulouse, , France

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Local Institution - 0055

Bonn, , Germany

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Local Institution - 0131

Cologne, , Germany

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Local Institution - 0123

Erlangen, , Germany

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Local Institution - 0053

Frankfurt am Main, , Germany

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Local Institution - 0124

Freiburg im Breisgau, , Germany

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Local Institution - 0057

Hamburg, , Germany

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Local Institution - 0056

Heidelberg, , Germany

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Local Institution - 0130

Munich, , Germany

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Local Institution - 0054

Münster, , Germany

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Local Institution - 0058

Regensburg, , Germany

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Local Institution - 0059

Tübingen, , Germany

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Local Institution - 0094

Petah Tikva, , Israel

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Local Institution - 0093

Tel Aviv, , Israel

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Local Institution - 0088

Bologna, , Italy

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Milan, , Italy

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Padua, , Italy

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Local Institution - 0127

Rozzano (milano), , Italy

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Local Institution - 0090

Siena, , Italy

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Torino, , Italy

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Local Institution - 0110

Nagoya, Aichi-ken, Japan

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Local Institution - 0099

Chiba, Chiba, Japan

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Local Institution - 0100

Hiroshima, Hiroshima, Japan

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Local Institution - 0101

Sapporo, Hokkaido, Japan

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Local Institution - 0105

Kobe, Hyōgo, Japan

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Local Institution - 0116

Tsukuba, Ibaraki, Japan

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Local Institution - 0103

Kanazawa, Ishikawa-ken, Japan

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Local Institution - 0102

Kagoshima, Kagoshima-ken, Japan

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Local Institution - 0118

Sagamihara-shi, Kanagawa, Japan

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Local Institution - 0106

Kumamoto, Kumamoto, Japan

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Local Institution - 0120

Okayama, Okayama-ken, Japan

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Local Institution - 0104

Hirakata-shi, Osaka, Japan

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Local Institution - 0112

Suita, Osaka, Japan

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Local Institution - 0121

Hidaka-shi, Saitama, Japan

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Local Institution - 0114

Bunkyo-ku, Tokyo, Japan

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Local Institution - 0111

Chuo-ku, Tokyo, Japan

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Local Institution - 0107

Mitaka-shi, Tokyo, Japan

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Local Institution - 0115

Shinjuku-ku, Tokyo, Japan

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Local Institution - 0117

Yamagata, Yamagata, Japan

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Local Institution - 0109

Kyoto, , Japan

Site Status

Local Institution - 0108

Kyoto, , Japan

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Local Institution - 0073

Rotterdam, South Holland, Netherlands

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Local Institution - 0075

Amsterdam, , Netherlands

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Local Institution - 0074

Groningen, , Netherlands

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Local Institution - 0072

Utrecht, , Netherlands

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Local Institution - 0083

Oslo, , Norway

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Local Institution - 0086

Gdansk, , Poland

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Local Institution - 0132

Warsaw, , Poland

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Local Institution - 0095

Moscow, , Russia

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Local Institution - 0097

Moscow, , Russia

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Local Institution - 0126

Badalona-barcelona, , Spain

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Local Institution - 0078

Barcelona, , Spain

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Local Institution - 0125

Barcelona, , Spain

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Local Institution - 0077

Madrid, , Spain

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Local Institution - 0076

Madrid, , Spain

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Local Institution - 0080

Santiago Compostela, , Spain

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Local Institution - 0079

Valencia, , Spain

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Local Institution - 0081

Lund, , Sweden

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Local Institution - 0082

Solna, , Sweden

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Local Institution - 0065

Geneva, , Switzerland

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Local Institution - 0064

Lausanne, , Switzerland

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Local Institution - 0063

Zurich, , Switzerland

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Local Institution - 0066

Manchester, Greater Manchester, United Kingdom

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Local Institution - 0119

Sutton, Surrey, United Kingdom

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Local Institution - 0068

Glasgow, , United Kingdom

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Local Institution - 0067

London, , United Kingdom

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Countries

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United States Australia Austria Belgium Canada Denmark France Germany Israel Italy Japan Netherlands Norway Poland Russia Spain Sweden Switzerland United Kingdom

References

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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.

Reference Type DERIVED
PMID: 35511454 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32691060 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2015-004722-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CA209-548

Identifier Type: -

Identifier Source: org_study_id

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