A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC) (IMbrave152)

NCT ID: NCT05904886

Last Updated: 2025-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

687 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-14

Study Completion Date

2026-09-01

Brief Summary

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The purpose of this study is to assess the efficacy and safety of tiragolumab, an anti-TIGIT monoclonal antibody, when administered in combination with atezolizumab and bevacizumab as first-line treatment, in participants with unresectable, locally advanced or metastatic HCC.

Per amendment version 5, following a memo issued by the Sponsor, participants receiving treatment in the atezolizumab plus bevacizumab plus tiragolumab arm are recommended to discontinue tiragolumab treatment unless the investigator decides the benefit outweighs the risk. Participants receiving treatment in atezolizumab plus bevacizumab plus placebo arm must discontinue placebo treatment. Participants may continue receiving active treatment(s) per protocol until loss of clinical benefit or unacceptable toxicity, whichever occurs first.

Detailed Description

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Conditions

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Hepatocellular Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
The study has been unblinded as of amendment version 5.

Study Groups

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Atezolizumab + Bevacizumab + Tiragolumab

Atezolizumab plus bevacizumab plus tiragolumab will be administered every 3 weeks (Q3W) until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type DRUG

Bevacizumab will be administered by IV infusion at a dose of 15 milligrams per kilogram (mg/kg) on Day 1 of each 21-day cycle.

Tiragolumab

Intervention Type DRUG

Tiragolumab will be administered by IV infusion at a fixed dose of 600 mg on Day 1 of each 21-day cycle.

Atezolizumab

Intervention Type DRUG

Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle.

Atezolizumab + Bevacizumab + Placebo

Atezolizumab, bevacizumab plus placebo will be administered Q3W until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Group Type PLACEBO_COMPARATOR

Bevacizumab

Intervention Type DRUG

Bevacizumab will be administered by IV infusion at a dose of 15 milligrams per kilogram (mg/kg) on Day 1 of each 21-day cycle.

Placebo

Intervention Type OTHER

Placebo matching tiragolumab will be administered by IV infusion on Day 1 of each 21-day cycle.

Atezolizumab

Intervention Type DRUG

Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle.

Interventions

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Bevacizumab

Bevacizumab will be administered by IV infusion at a dose of 15 milligrams per kilogram (mg/kg) on Day 1 of each 21-day cycle.

Intervention Type DRUG

Tiragolumab

Tiragolumab will be administered by IV infusion at a fixed dose of 600 mg on Day 1 of each 21-day cycle.

Intervention Type DRUG

Placebo

Placebo matching tiragolumab will be administered by IV infusion on Day 1 of each 21-day cycle.

Intervention Type OTHER

Atezolizumab

Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle.

Intervention Type DRUG

Other Intervention Names

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Tecentriq; MPDL3280A; RO5541267 Avastin MTIG7192A; RO7092284

Eligibility Criteria

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Inclusion Criteria

* Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic participants
* Disease that is not amenable to curative surgical and/or locoregional therapies
* No prior systemic treatment for locally advanced or metastatic and/or unresectable HCC-measurable disease according to RECIST v1.1
* Eastern cooperative oncology group (ECOG) performance status of 0 or 1 within 7 days prior to randomization
* Child-pugh Class A within 7 days prior to randomization
* Adequate hematologic and end-organ function
* Female participants of childbearing potential must be willing to avoid pregnancy within 5 months after the final dose of atezolizumab, within 6 months after the final dose of bevacizumab, and within 90 days after the final dose of tiragolumab/placebo
* Male participants with a female partner of childbearing potential or pregnant female partner must remain abstinent or use a condom during the treatment period and for 6 months after the final dose of bevacizumab and for 90 days after the final dose of tiragolumab/placebo to avoid exposing the embryo.

Exclusion Criteria

* Pregnancy or breastfeeding within 5 months after the final dose of atezolizumab, within 6 months after the final dose of bevacizumab, and within 90 days after the final dose of tiragolumab/placebo
* Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Treatment with locoregional therapy to liver within 28 days prior to initiation of study treatment, or non-recovery from side effects of any such procedure
* Treatment with systemic immunostimulatory agents
* Treatment with systemic immunosuppressive medication
* Untreated or incompletely treated esophageal and/or gastric varices with bleeding or that are at high risk for bleeding
* A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
* Active or history of autoimmune disease or immune deficiency
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
* History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
* Mixed histology or other subtypes/variants of HCC, including, but not limited to, known liver adenocarcinoma, fibrolamellar HCC, sarcomatoid HCC, other rare HCC variant, or mixed cholangiocarcinoma and HCC
* Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV)
* Acute epstein-barr virus (EBV) infection or known or suspected chronic active EBV infection
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Chugai Pharmaceutical

INDUSTRY

Sponsor Role collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Genesis Cancer Center

Hot Springs, Arkansas, United States

Site Status

UCSF Fresno at Community Cancer Institute

Clovis, California, United States

Site Status

City of Hope Cancer Center

Duarte, California, United States

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University of California San Diego Moores Cancer Center

La Jolla, California, United States

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University of Southern California

Los Angeles, California, United States

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Stanford Cancer Center

Palo Alto, California, United States

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Va Palo Alto Health Care System

Palo Alto, California, United States

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UCLA Cancer Center

Santa Monica, California, United States

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Hartford Healthcare Cancer Institute at Hartford Hospital

Hartford, Connecticut, United States

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MedStar Washington Hosp Center

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

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Florida Cancer Specialists - Fort Myers (Broadway)

Fort Myers, Florida, United States

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Miami VA Healthcare System

Miami, Florida, United States

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Florida Cancer Specialist, North Region

St. Petersburg, Florida, United States

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University of Illinois

Chicago, Illinois, United States

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Norton Cancer Institute - Audubon

Louisville, Kentucky, United States

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Ochsner Cancer Inst.

New Orleans, Louisiana, United States

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Mercy Medical Center

Baltimore, Maryland, United States

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Henry Ford Health System

Detroit, Michigan, United States

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Cancer & Hematology Centers of Western Michigan

Grand Rapids, Michigan, United States

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Mayo Clinic Rochester

Rochester, Minnesota, United States

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Minnesota Oncology Hematology Woodbury

Woodbury, Minnesota, United States

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Washington Uni School of Medicine

St Louis, Missouri, United States

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NYU Langone

New York, New York, United States

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Icahn School of Medicine at Mount Sinai

New York, New York, United States

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Columbia University

New York, New York, United States

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Montefiore Medical Center

The Bronx, New York, United States

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James J Peters VA Hospital / Mental Illness Research Education and Clinic Center

The Bronx, New York, United States

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University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

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Thomas Jefferson Uni

Philadelphia, Pennsylvania, United States

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North Texas VA Medical Center

Dallas, Texas, United States

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Kelsey Seybold Clnic

Houston, Texas, United States

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Virginia Mason Medical Center

Seattle, Washington, United States

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Swedish Cancer Inst.

Seattle, Washington, United States

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Univ of Wisconsin-Madison

Madison, Wisconsin, United States

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Cliniques Universitaires St-Luc

Brussels, , Belgium

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UZ Antwerpen

Edegem, , Belgium

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AZ Delta (Campus Rumbeke)

Roeselare, , Belgium

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CEDOES - Diagnóstico e Pesquisa

Vitória, Espírito Santo, Brazil

Site Status

Oncoclínicas do Brasil - BELO HORIZONTE

Belo Horizonte, Minas Gerais, Brazil

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Hospital do Cancer de Pernambuco - HCP

Recife, Pernambuco, Brazil

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Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

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Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

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Hospital de Cancer de Barretos

Barretos, São Paulo, Brazil

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Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, Brazil

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Clinicas Oncologicas Integradas - COI

Rio de Janeiro, , Brazil

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Juravinski Hospital

Hamilton, Ontario, Canada

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Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

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Jewish General Hospital

Montreal, Quebec, Canada

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McGill University Health Centre - Glen Site

Montreal, Quebec, Canada

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Baoji Central Hospital

Baoji, , China

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Beijing Cancer Hospital

Beijing, , China

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The First Hospital of Jilin University

Changchun, , China

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Peoples Hospital of Hunan Province

Changsha, , China

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Hunan Cancer Hospital

Changsha, , China

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West China Hospital - Sichuan University

Chengdu, , China

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The First Affliated Hospital Of Fujian Medical University

Fuzhou, , China

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Mengchao Hepatobiliary Hospital Of Fujian Medical University

Fuzhou, , China

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Nanfang Hospital, Southern Medical University

Guangzhou, , China

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Sun yat-sen University Cancer Center

Guangzhou, , China

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The First Affiliated Hospital of College of Medicine, Zhejiang University

Hangzhou, , China

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Zhejiang Provincial People?s Hospital

Hangzhou, , China

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Harbin Medical University Cancer Hospital

Harbin, , China

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Anhui Provincial Hospital

Hefei, , China

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The Second Affiliated Hospital of Anhui Medical University

Hefei, , China

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Lishui Central Hospital

Lishui, , China

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Zhongshan Hospital Fudan Unvierstiy

Shanghai, , China

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Renji Hospital Shanghai Jiaotong University School of Medicine

Shanghai, , China

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Shengjing Hospital of China Medical University

Shenyang, , China

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Tianjin Cancer Hospital

Tianjin, , China

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Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, , China

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First Affiliated Hospital of Medical College of Xi'an Jiaotong University

Xi'an, , China

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Xi'an Inernational Medical Center Hospital

Xi'an, , China

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Polyclinique Internationale Sainte Anne- Marie (PISAM)

Abidjan, , Côte d’Ivoire

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Centre National d'Oncologie Médicale et de Radiothérapie Alassane Ouattara (CNRAO)

Abidjan, , Côte d’Ivoire

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CHU CAEN - Hôpital de la Côte de Nacre

Caen, , France

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CHRU de Lille - Hopital Claude Huriez

Lille, , France

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Hopital Dupuytren

Limoges, , France

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Fondation Hopital Saint Joseph

Marseille, , France

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Hopital Hotel Dieu Et Hme

Nantes, , France

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APHP - Hopital Saint Antoine

Paris, , France

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Hopital Robert Debre

Reims, , France

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Centre Hospitalier Valence

Valence, , France

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Hopitaux de Brabois - Gastro-Entereologie

Vandœuvre-lès-Nancy, , France

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Hopital Paul Brousse

Villejuif, , France

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Klinikum Esslingen

Esslingen am Neckar, , Germany

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Universitätsklinikum Magdeburg Klinik für Gastroenterologie und Hepatologie

Magdeburg, , Germany

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Uniklinik Mainz

Mainz, , Germany

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Universität Tübingen

Tübingen, , Germany

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KBTH

Accra, , Ghana

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Sweden Ghana Medical Center

Accra, , Ghana

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Queen Mary Hospital

Hong Kong, , Hong Kong

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Prince of Wales Hosp

Shatin, , Hong Kong

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Az. Osp. G. Panico

Tricase, Apulia, Italy

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A.O. S. Orsola Malpighi

Bologna, Emilia-Romagna, Italy

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Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio, Italy

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Az. Osp. Uni Ria San Martino

Genoa, Liguria, Italy

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IRCCS Istituto Clinico Humanitas

Rozzano, Lombardy, Italy

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A.O.U. Policlinico Paolo Giaccone

Palermo, Sicily, Italy

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A.O.U.I. Verona-Ospedale Policlinico G.B. Rossi Borgo Roma

Verona, Veneto, Italy

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Fujita Health University Hospital

Aichi, , Japan

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Chiba University Hospital

Chiba, , Japan

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National Cancer Center Hospital East

Chiba, , Japan

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Ehime Prefectural Central Hospital

Ehime, , Japan

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Kurume University Hospital

Fukuoka, , Japan

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Hiroshima University Hospital

Hiroshima, , Japan

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Sapporo Kosei General Hospital

Hokkaido, , Japan

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Hokkaido University Hospital

Hokkaido, , Japan

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Kanazawa University Hospital

Ishikawa, , Japan

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Toranomon Branch Hospital

Kanagawa, , Japan

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Kanagawa Cancer Center

Kanagawa, , Japan

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Kitasato University Hospital

Kanagawa, , Japan

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University Hospital Kyoto Prefectural University of Medicine

Kyoto, , Japan

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Kyoto University Hospital

Kyoto, , Japan

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Iwate Medical University Hospital

Numakunai, , Japan

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The University of Osaka Hospital

Osaka, , Japan

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Kindai University Hospital

Osaka, , Japan

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Jichi Medical University Hospital

Tochigi, , Japan

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Toranomon Hospital

Tokyo, , Japan

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Japanese Red Cross Musashino Hospital

Tokyo, , Japan

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University of Nairobi - Institute of Tropical and Infectious Diseases

Nairobi, , Kenya

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OncoMed

Mexico City, Mexico CITY (federal District), Mexico

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Centro Medico Nacional Siglo Xxi - Imss

Mexico City, Mexico CITY (federal District), Mexico

Site Status

Instituto Nacional de Ciencias Médicas Y de Nutricion Salvador Zubirán

Mexico City, Mexico CITY (federal District), Mexico

Site Status

Centro de Investigacion Clinica de Oaxaca

Oaxaca City, Oaxaca, Mexico

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Auckland City Hospital

Auckland, , New Zealand

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Christchurch Hospital

Christchurch, , New Zealand

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Wellington Hospital

Wellington, , New Zealand

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Jos University Teaching Hospital

Jos, , Nigeria

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Lagos University Teaching Hospital Lagos (LUTH), Lagos State

Lagos, , Nigeria

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ID Clinic

Mysłowice, , Poland

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NIO im Marii Sklodowskiej-Curie

Warsaw, , Poland

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PanOncology Trials

San Juan, , Puerto Rico

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National Cancer Centre

Singapore, , Singapore

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Charlotte Maxeke Johannesburg Academic Hospital

Johannesburg, , South Africa

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Limpopo Cancer Research Institute

Polokwane, , South Africa

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National Cancer Center

Goyang-si, , South Korea

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CHA Bundang Medical Center

Gyeonggi-do, , South Korea

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Chonnam National University Hwasun Hospital

Jeollanam-do, , South Korea

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Severance Hospital, Yonsei University Health System

Seoul, , South Korea

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Seoul National University Hospital

Seoul, , South Korea

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Asan Medical Center

Seoul, , South Korea

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Samsung Medical Center

Seoul, , South Korea

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Ulsan University Hosiptal

Ulsan, , South Korea

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Hospital de Navarra

Navarra, Navarre, Spain

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Clinica Universitaria de Navarra

Pamplona/iruña, Navarre, Spain

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Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, Spain

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Hospital Universitari Vall d'Hebron

Barcelona, , Spain

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Hospital Duran i Reynals

Barcelona, , Spain

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Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico

Jaén, , Spain

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Hospital General Universitario Gregorio Marañon

Madrid, , Spain

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Clinica Universitaria de Navarra de Madrid;Servicio de Hepatologia

Madrid, , Spain

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Hospital Clinico San Carlos

Madrid, , Spain

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Hospital Universitario Puerta de Hierro

Madrid, , Spain

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Hospital Clinico de Valencia

Valencia, , Spain

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China Medical University Hospital

Taichung, , Taiwan

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National Cheng Kung University Hospital

Tainan, , Taiwan

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Chi-Mei Medical Centre

Tainan, , Taiwan

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National Taiwan Uni Hospital

Taipei, , Taiwan

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Chang Gung Medical Foundation - Linkou

Taoyuan District, , Taiwan

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Chulalongkorn Hospital

Bangkok, , Thailand

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Ramathibodi Hospital

Bangkok, , Thailand

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Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, , Thailand

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Khon Kaen Uni

Khon Kaen, , Thailand

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Adana Baskent University Medical Faculty

Adana, , Turkey (Türkiye)

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Ankara Bilkent City Hospital

Ankara, , Turkey (Türkiye)

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Gazi Uni Medical Faculty Hospital

Ankara, , Turkey (Türkiye)

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Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi

Edirne, , Turkey (Türkiye)

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?zmir Medical Point

Kar?iyaka, , Turkey (Türkiye)

Site Status

Uganda Cancer Institute

Kampala, , Uganda

Site Status

Western General Hospital

Edinburgh, , United Kingdom

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Royal Free Hospital

London, , United Kingdom

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Hammersmith Hospital

London, , United Kingdom

Site Status

Countries

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Morocco United States Belgium Brazil Canada China Côte d’Ivoire France Germany Ghana Hong Kong Italy Japan Kenya Mexico New Zealand Nigeria Poland Puerto Rico Singapore South Africa South Korea Spain Taiwan Thailand Turkey (Türkiye) Uganda United Kingdom

References

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Badhrinarayanan S, Cotter C, Zhu H, Lin YC, Kudo M, Li D. IMbrave152/SKYSCRAPER-14: a Phase III study of atezolizumab, bevacizumab and tiragolumab in advanced hepatocellular carcinoma. Future Oncol. 2024;20(28):2049-2057. doi: 10.1080/14796694.2024.2355863. Epub 2024 Jun 10.

Reference Type DERIVED
PMID: 38861301 (View on PubMed)

Other Identifiers

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2023-503422-39-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CO44668

Identifier Type: -

Identifier Source: org_study_id