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

Recruitment Status
ACTIVE, NOT RECRUITING
(See Contacts and Locations)Verified November 2025 by Hoffmann-La Roche
Sponsor
Hoffmann-La Roche
Information Provided by (Responsible Party)
Hoffmann-La Roche
Clinicaltrials.gov Identifier
NCT05904886
Other Study ID Numbers:
CO44668
First Submitted
May 22, 2023
First Posted
June 14, 2023
Last Update Posted
December 30, 2025
Last Verified
November 2025

ClinicalTrials.gov processed this data on December 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Hepatocellular Carcinoma
Drug: AtezolizumabDrug: Atezolizumab

Study Design

Study TypeInterventional
Actual Enrollment687 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA Phase III, Randomized, Double-blind, Placebo-controlled Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
Study Start DateSeptember 13, 2023
Actual Primary Completion DateMay 7, 2025
Actual Study Completion Date3mos 2w from now

Groups and Cohorts

Group/CohortIntervention/Treatment
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.
Drug: 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.
Atezolizumab + Bevacizumab + Placebo
Atezolizumab, bevacizumab plus placebo will be administered Q3W until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Drug: 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.

Outcome Measures

Primary Outcome Measures
  1. Investigator-assessed Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
  2. Overall Survival (OS)
Secondary Outcome Measures
  1. Investigator-assessed Confirmed Objective Response Rate (ORR) According to RECIST v1.1
  2. Investigator-assessed Duration of Response (DOR) According to RECIST v1.1
  3. Investigator-assessed PFS Rate According to RECIST v1.1 at 6 and 12 Months
  4. OS Rate at 1 and 2 Years
  5. Investigator-assessed PFS According to HCC mRECIST
  6. Investigator-assessed Confirmed ORR According to HCC mRECIST
  7. Investigator-assessed DOR According to HCC mRECIST
  8. Time to Confirmed Deterioration (TTCD) Assessed Using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer 30 (EORTC QLQ-C30) Subscales
    The following subscales of the EORTC QLQ-C30 will be used for the assessment: global health status/quality-of-life (GHS/QoL), physical functioning and role functioning. GHS and QoL are scored on a 7-point scale: 1=Very poor to 7=Excellent. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with a higher score indicating a worse outcome. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. A higher score indicates a better outcome.
  9. Change from Baseline in GHS/QoL, Physical Functioning, and Role Functioning Assessed Using the EORTC QLQ-C30
    GHS and QoL are scored on a 7-point scale: 1=Very poor to 7=Excellent. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with a higher score indicating a worse outcome. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. A higher score indicates a better outcome.
  10. Percentage of Participants With Adverse Events (AEs)
  11. Serum Concentrations of Atezolizumab
  12. Serum Concentrations of Tiragolumab
  13. Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab
  14. Percentage of Participants With ADAs to Atezolizumab

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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.

Contacts and Locations

Sponsors and CollaboratorsHoffmann-La Roche
Locations
Genesis Cancer Center | Hot Springs Arkansas, United States, 71913UCSF Fresno at Community Cancer Institute | Clovis California, United States, 93611City of Hope Cancer Center | Duarte California, United States, 91010University of California San Diego Moores Cancer Center | La Jolla California, United States, 92037University of Southern California | Los Angeles California, United States, 90033Stanford Cancer Center | Palo Alto California, United States, 94304Va Palo Alto Health Care System | Palo Alto California, United States, 94304UCLA Cancer Center | Santa Monica California, United States, 90404Hartford Healthcare Cancer Institute at Hartford Hospital | Hartford Connecticut, United States, 06106MedStar Washington Hosp Center | Washington D.C. District of Columbia, United States, 20010Florida Cancer Specialists - Fort Myers (Broadway) | Fort Myers Florida, United States, 33901Miami VA Healthcare System | Miami Florida, United States, 33125Florida Cancer Specialist, North Region | St. Petersburg Florida, United States, 33705University of Illinois | Chicago Illinois, United States, 60612Norton Cancer Institute - Audubon | Louisville Kentucky, United States, 40217Ochsner Cancer Inst. | New Orleans Louisiana, United States, 70121Mercy Medical Center | Baltimore Maryland, United States, 21202Henry Ford Health System | Detroit Michigan, United States, 48202Cancer & Hematology Centers of Western Michigan | Grand Rapids Michigan, United States, 49503Mayo Clinic Rochester | Rochester Minnesota, United States, 55905Minnesota Oncology Hematology Woodbury | Woodbury Minnesota, United States, 55125Washington Uni School of Medicine | St Louis Missouri, United States, 63110NYU Langone | New York New York, United States, 10016Icahn School of Medicine at Mount Sinai | New York New York, United States, 10029Columbia University | New York New York, United States, 10032-3725Montefiore Medical Center | The Bronx New York, United States, 10461James J Peters VA Hospital / Mental Illness Research Education and Clinic Center | The Bronx New York, United States, 10468University of North Carolina at Chapel Hill | Chapel Hill North Carolina, United States, 27514Thomas Jefferson Uni | Philadelphia Pennsylvania, United States, 19107North Texas VA Medical Center | Dallas Texas, United States, 75216Kelsey Seybold Clnic | Houston Texas, United States, 77005Virginia Mason Medical Center | Seattle Washington, United States, 98101Swedish Cancer Inst. | Seattle Washington, United States, 98104Univ of Wisconsin-Madison | Madison Wisconsin, United States, 53792Cliniques Universitaires St-Luc | Brussels , Belgium, 1200UZ Antwerpen | Edegem , Belgium, 2650AZ Delta (Campus Rumbeke) | Roeselare , Belgium, 8800CEDOES - Diagnóstico e Pesquisa | Vitória Espírito Santo, Brazil, 29055-450Oncoclínicas do Brasil - BELO HORIZONTE | Belo Horizonte Minas Gerais, Brazil, 30170-080Hospital do Cancer de Pernambuco - HCP | Recife Pernambuco, Brazil, 50040-000Santa Casa de Misericordia de Porto Alegre | Porto Alegre Rio Grande do Sul, Brazil, 90020-090Hospital Sao Lucas - PUCRS | Porto Alegre Rio Grande do Sul, Brazil, 90610-000Hospital de Cancer de Barretos | Barretos São Paulo, Brazil, 14784-400Instituto do Cancer do Estado de Sao Paulo - ICESP | São Paulo São Paulo, Brazil, 01246-000Clinicas Oncologicas Integradas - COI | Rio de Janeiro , Brazil, 22290-160Juravinski Hospital | Hamilton Ontario, Canada, L8V 1C3Sunnybrook Health Sciences Centre | Toronto Ontario, Canada, M4N 3M5Jewish General Hospital | Montreal Quebec, Canada, H3T 1E2McGill University Health Centre - Glen Site | Montreal Quebec, Canada, H4A 3J1Baoji Central Hospital | Baoji , China, 721008Beijing Cancer Hospital | Beijing , China, 100142The First Hospital of Jilin University | Changchun , China, 130021Peoples Hospital of Hunan Province | Changsha , China, 410007Hunan Cancer Hospital | Changsha , China, 410013West China Hospital - Sichuan University | Chengdu , China, 610047Mengchao Hepatobiliary Hospital Of Fujian Medical University | Fuzhou , China, 350025Nanfang Hospital, Southern Medical University | Guangzhou , China, 510515Sun yat-sen University Cancer Center | Guangzhou , China, The First Affiliated Hospital of College of Medicine, Zhejiang University | Hangzhou , China, 310003Zhejiang Provincial People?s Hospital | Hangzhou , China, 310014Harbin Medical University Cancer Hospital | Harbin , China, 150081Anhui Provincial Hospital | Hefei , China, 230001The Second Affiliated Hospital of Anhui Medical University | Hefei , China, 230601Lishui Central Hospital | Lishui , China, 323000Zhongshan Hospital Fudan Unvierstiy | Shanghai , China, 200032Renji Hospital Shanghai Jiaotong University School of Medicine | Shanghai , China, 200127Shengjing Hospital of China Medical University | Shenyang , China, 110004Tianjin Cancer Hospital | Tianjin , China, 300060Tongji Hospital Tongji Medical College Huazhong University of Science and Technology | Wuhan , China, 430030First Affiliated Hospital of Medical College of Xi'an Jiaotong University | Xi'an , China, 710061Xi'an Inernational Medical Center Hospital | Xi'an , China, 710119Polyclinique Internationale Sainte Anne- Marie (PISAM) | Abidjan , Côte d’Ivoire, BP 1463 AbidjanCentre National d'Oncologie Médicale et de Radiothérapie Alassane Ouattara (CNRAO) | Abidjan , Côte d’Ivoire, CHU CAEN - Hôpital de la Côte de Nacre | Caen , France, 14033CHRU de Lille - Hopital Claude Huriez | Lille , France, 59037Hopital Dupuytren | Limoges , France, 87042Fondation Hopital Saint Joseph | Marseille , France, 13285Hopital Hotel Dieu Et Hme | Nantes , France, 44093APHP - Hopital Saint Antoine | Paris , France, 75571Hopital Robert Debre | Reims , France, 51092Centre Hospitalier Valence | Valence , France, 26953Hopitaux de Brabois - Gastro-Entereologie | Vandœuvre-lès-Nancy , France, 54511Hopital Paul Brousse | Villejuif , France, 94804Klinikum Esslingen | Esslingen am Neckar , Germany, 73730Universitätsklinikum Magdeburg Klinik für Gastroenterologie und Hepatologie | Magdeburg , Germany, 39120Uniklinik Mainz | Mainz , Germany, 55131Universität Tübingen | Tübingen , Germany, 72076KBTH | Accra , Ghana, 0000Sweden Ghana Medical Center | Accra , Ghana, Queen Mary Hospital | Hong Kong , Hong Kong, Prince of Wales Hosp | Shatin , Hong Kong, Az. Osp. G. Panico | Tricase Apulia, Italy, A.O. S. Orsola Malpighi | Bologna Emilia-Romagna, Italy, 40138Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Rome Lazio, Italy, 00168Az. Osp. Uni Ria San Martino | Genoa Liguria, Italy, 16132IRCCS Istituto Clinico Humanitas | Rozzano Lombardy, Italy, 20089A.O.U. Policlinico Paolo Giaccone | Palermo Sicily, Italy, 90127A.O.U.I. Verona-Ospedale Policlinico G.B. Rossi Borgo Roma | Verona Veneto, Italy, 37134Fujita Health University Hospital | Aichi , Japan, 470-1192Chiba University Hospital | Chiba , Japan, 260-8677National Cancer Center Hospital East | Chiba , Japan, 277-8577Ehime Prefectural Central Hospital | Ehime , Japan, 790-0024Kurume University Hospital | Fukuoka , Japan, 830-0011Hiroshima University Hospital | Hiroshima , Japan, 734-8551Sapporo Kosei General Hospital | Hokkaido , Japan, 060-0033Hokkaido University Hospital | Hokkaido , Japan, 060-8648Kanazawa University Hospital | Ishikawa , Japan, 920-8641Toranomon Branch Hospital | Kanagawa , Japan, 213-8587Kanagawa Cancer Center | Kanagawa , Japan, 241-8515Kitasato University Hospital | Kanagawa , Japan, 252-0375University Hospital Kyoto Prefectural University of Medicine | Kyoto , Japan, 602-8566Kyoto University Hospital | Kyoto , Japan, 606-8507Iwate Medical University Hospital | Numakunai , Japan, 028-3695The University of Osaka Hospital | Osaka , Japan, 565-0871Kindai University Hospital | Osaka , Japan, 589-8511Jichi Medical University Hospital | Tochigi , Japan, 329-0498Toranomon Hospital | Tokyo , Japan, 105-8470Japanese Red Cross Musashino Hospital | Tokyo , Japan, 180-8610University of Nairobi - Institute of Tropical and Infectious Diseases | Nairobi , Kenya, OncoMed | Mexico City Mexico CITY (federal District), Mexico, 03100Centro Medico Nacional Siglo Xxi - Imss | Mexico City Mexico CITY (federal District), Mexico, 06720Instituto Nacional de Ciencias Médicas Y de Nutricion Salvador Zubirán | Mexico City Mexico CITY (federal District), Mexico, 14000Centro de Investigacion Clinica de Oaxaca | Oaxaca City Oaxaca, Mexico, 68020Auckland City Hospital | Auckland , New Zealand, 1023Christchurch Hospital | Christchurch , New Zealand, 8011Wellington Hospital | Wellington , New Zealand, 6021Jos University Teaching Hospital | Jos , Nigeria, 930232Lagos University Teaching Hospital Lagos (LUTH), Lagos State | Lagos , Nigeria, ID Clinic | Mysłowice , Poland, 41-400NIO im Marii Sklodowskiej-Curie | Warsaw , Poland, 02-034PanOncology Trials | San Juan , Puerto Rico, 00935National Cancer Centre | Singapore , Singapore, 168583Charlotte Maxeke Johannesburg Academic Hospital | Johannesburg , South Africa, 2193Limpopo Cancer Research Institute | Polokwane , South Africa, 0700National Cancer Center | Goyang-si , South Korea, 10408CHA Bundang Medical Center | Gyeonggi-do , South Korea, 13496Chonnam National University Hwasun Hospital | Jeollanam-do , South Korea, 58128Severance Hospital, Yonsei University Health System | Seoul , South Korea, 003-722Seoul National University Hospital | Seoul , South Korea, 03080Asan Medical Center | Seoul , South Korea, 05505Samsung Medical Center | Seoul , South Korea, 06351Ulsan University Hosiptal | Ulsan , South Korea, 44033Hospital de Navarra | Navarra Navarre, Spain, 31008Clinica Universitaria de Navarra | Pamplona/iruña Navarre, Spain, 31008Hospital Universitario Central de Asturias | Oviedo Principality of Asturias, Spain, 33011Hospital Universitari Vall d'Hebron | Barcelona , Spain, 08035Hospital Duran i Reynals | Barcelona , Spain, 08907Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico | Jaén , Spain, 23007Hospital General Universitario Gregorio Marañon | Madrid , Spain, 28007Clinica Universitaria de Navarra de Madrid;Servicio de Hepatologia | Madrid , Spain, 28027Hospital Clinico San Carlos | Madrid , Spain, 28040Hospital Universitario Puerta de Hierro | Madrid , Spain, 28222Hospital Clinico de Valencia | Valencia , Spain, 46010China Medical University Hospital | Taichung , Taiwan, 404National Cheng Kung University Hospital | Tainan , Taiwan, 00704Chi-Mei Medical Centre | Tainan , Taiwan, 710National Taiwan Uni Hospital | Taipei , Taiwan, 100Chang Gung Medical Foundation - Linkou | Taoyuan , Taiwan, 333Chulalongkorn Hospital | Bangkok , Thailand, 10330Ramathibodi Hospital | Bangkok , Thailand, 10400Maharaj Nakorn Chiang Mai Hospital | Chiang Mai , Thailand, 50200Khon Kaen Uni | Khon Kaen , Thailand, 40002Adana Baskent University Medical Faculty | Adana , Turkey (Türkiye), 01220Ankara Bilkent City Hospital | Ankara , Turkey (Türkiye), 06490Gazi Uni Medical Faculty Hospital | Ankara , Turkey (Türkiye), 06500Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi | Edirne , Turkey (Türkiye), 22030?zmir Medical Point | Kar?iyaka , Turkey (Türkiye), 35575Uganda Cancer Institute | Kampala , Uganda, Western General Hospital | Edinburgh , United Kingdom, EH4 2XURoyal Free Hospital | London , United Kingdom, NW3 2QGHammersmith Hospital | London , United Kingdom, W12 0HS
Investigators
Study Director: Clinical Trials, Hoffmann-La Roche