A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (IMbrave152)
- Conditions
- Carcinoma, Hepatocellular
- Interventions
- Registration Number
- NCT05904886
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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 hepatocellular carcinoma (HCC).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 650
- 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
- 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.
- 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 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atezolizumab + Bevacizumab + Tiragolumab 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. Atezolizumab + Bevacizumab + Placebo Placebo Atezolizumab, bevacizumab plus placebo will be administered every 3 weeks (Q3W) until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Atezolizumab + Bevacizumab + Tiragolumab Atezolizumab 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. Atezolizumab + Bevacizumab + Tiragolumab Bevacizumab 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. Atezolizumab + Bevacizumab + Placebo Atezolizumab Atezolizumab, bevacizumab plus placebo will be administered every 3 weeks (Q3W) until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Atezolizumab + Bevacizumab + Placebo Bevacizumab Atezolizumab, bevacizumab plus placebo will be administered every 3 weeks (Q3W) until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
- Primary Outcome Measures
Name Time Method Investigator-Assessed Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 36 months) Overall Survival (OS) From randomization to death from any cause (up to approximately 36 months)
- Secondary Outcome Measures
Name Time Method Investigator-Assessed Duration of Objective Response (DOR) According to RECIST v1.1 From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 36 months) OS Rate at 1 and 2 Years Year 1, Year 2 Time to Confirmed Deterioration (TTCD) Assessed Using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer 30 (QLQ-C30) Subscales From randomization up to approximately 36 months 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.
Change from Baseline in GHS/QoL, Physical Functioning, and Role Functioning Assessed Using the EORTC QLQ-C30 From baseline up to approximately 36 months 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.
Serum Concentrations of Atezolizumab Prior to the first infusion and 30 minutes after atezolizumab infusion on Day 1 of Cycle 1 (cycle = 21 days), prior to infusion on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit (up to approximately 36 months) Investigator-Assessed PFS Rate According to RECIST v1.1 at 6 and 12 Months Month 6, Month 12 Percentage of Participants With Adverse Events Up to approximately 36 months Serum Concentrations of Tiragolumab Prior to the first infusion and 30 minutes after tiragolumab infusion on Day 1 of Cycle 1 (cycle = 21 days), prior to infusion on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit (up to approximately 36 months) Investigator-Assessed DOR According to HCC mRECIST From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 36 months) Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab Prior to the first infusion on Day 1 of Cycles (cycle = 21 days) 1, 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit (up to approximately 36 months) Investigator-Assessed Confirmed Objective Response Rate (ORR) According to RECIST v1.1 From randomization up to approximately 36 months Investigator-Assessed PFS According to Hepatocellular Carcinoma (HCC) Modified RECIST (mRECIST) From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 36 months) Investigator-Assessed Confirmed ORR According to HCC mRECIST From randomization up to approximately 36 months Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab Prior to the first infusion on Day 1 of Cycles (cycle = 21 days) 1, 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit (up to approximately 36 months)
Trial Locations
- Locations (174)
AZ Delta (Campus Rumbeke)
🇧🇪Roeselare, Belgium
Oncoclínicas do Brasil - BELO HORIZONTE
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Ulsan University Hosiptal
🇰🇷Ulsan, Korea, Republic of
Hospital de Navarra
🇪🇸Navarra, Spain
Hospital Clinico de Valencia
🇪🇸Valencia, Spain
Maharaj Nakorn Chiang Mai Hospital
🇹🇭ChiangMai, Thailand
Khon Kaen Uni
🇹🇭Khon Kaen, Thailand
Adana Baskent University Medical Faculty
🇹🇷Adana, Turkey
Ankara Bilkent City Hospital
🇹🇷Ankara, Turkey
Gazi Uni Medical Faculty Hospital
🇹🇷Ankara, Turkey
Dicle University Faculty of Medicine
🇹🇷Diyarbakir, Turkey
Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
🇹🇷Edirne, Turkey
?zmir Medical Point
🇹🇷Kar?iyaka, Turkey
Uganda Cancer Institute
🇺🇬Kampala, Uganda
Western General Hospital
🇬🇧Edinburgh, United Kingdom
Royal Free Hospital
🇬🇧London, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Ochsner Cancer Inst.
🇺🇸New Orleans, Louisiana, United States
A.O.U.I. Verona-Ospedale Policlinico G.B. Rossi Borgo Roma
🇮🇹Verona, Veneto, Italy
Fujita Health University Hospital
🇯🇵Aichi, Japan
Chiba University Hospital
🇯🇵Chiba, Japan
National Cancer Center Hospital East
🇯🇵Chiba, Japan
Ehime Prefectural Central Hospital
🇯🇵Ehime, Japan
Kanagawa Cancer Center
🇯🇵Kanagawa, Japan
Lagos University Teaching Hospital Lagos (LUTH), Lagos State
🇳🇬Lagos, Nigeria
Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico
🇪🇸Jaen, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Clinica Universitaria de Navarra de Madrid;Servicio de Hepatologia
🇪🇸Madrid, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario Puerta de Hierro
🇪🇸Madrid, Spain
China Medical University Hospital
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Chi-Mei Medical Centre
🇨🇳Tainan, Taiwan
National Taiwan Uni Hospital
🇨🇳Taipei, Taiwan
Chang Gung Medical Foundation - Linkou
🇨🇳Taoyuan, Taiwan
Chulalongkorn Hospital
🇹🇭Bangkok, Thailand
Ramathibodi Hospital
🇹🇭Bangkok, Thailand
UZ Antwerpen
🇧🇪Edegem, Belgium
Hospital Duran i Reynals
🇪🇸Barcelona, Spain
Cliniques Universitaires St-Luc
🇧🇪Bruxelles, Belgium
Peoples Hospital of Hunan Province
🇨🇳Changsha, China
West China Hospital - Sichuan University
🇨🇳Chengdu City, China
The First Affliated Hospital Of Fujian Medical University
🇨🇳Fuzhou City, China
Tianjin Cancer Hospital
🇨🇳Tianjin, China
Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan City, China
First Affiliated Hospital of Medical College of Xi'an Jiaotong University
🇨🇳Xi'an, China
A.O.U. Policlinico Paolo Giaccone
🇮🇹Palermo, Sicilia, Italy
Xi'an Inernational Medical Center Hospital
🇨🇳Xi'an, China
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
Univ of Wisconsin-Madison
🇺🇸Madison, Wisconsin, United States
Genesis Cancer Center
🇺🇸Hot Springs, Arkansas, United States
UCSF Fresno at Community Cancer Institute
🇺🇸Clovis, California, United States
City of Hope Cancer Center
🇺🇸Duarte, California, United States
University of California San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Stanford Cancer Center
🇺🇸Palo Alto, California, United States
Va Palo Alto Health Care System
🇺🇸Palo Alto, California, United States
UCLA Cancer Center
🇺🇸Santa Monica, California, United States
Hartford Healthcare Cancer Institute at Hartford Hospital
🇺🇸Hartford, Connecticut, United States
MedStar Washington Hosp Center
🇺🇸Washington, District of Columbia, United States
Florida Cancer Specialists - Fort Myers (Broadway)
🇺🇸Fort Myers, Florida, United States
Miami VA Healthcare System
🇺🇸Miami, Florida, United States
Florida Cancer Specialist, North Region
🇺🇸Saint Petersburg, Florida, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Norton Cancer Institute - Audubon
🇺🇸Louisville, Kentucky, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Cancer & Hematology Centers of Western Michigan
🇺🇸Grand Rapids, Michigan, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Minnesota Oncology Hematology Woodbury
🇺🇸Woodbury, Minnesota, United States
Washington Uni School of Medicine
🇺🇸Saint Louis, Missouri, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
James J Peters VA Hospital / Mental Illness Research Education and Clinic Center
🇺🇸Bronx, New York, United States
NYU Langone
🇺🇸New York, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Columbia University
🇺🇸New York, New York, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Thomas Jefferson Uni
🇺🇸Philadelphia, Pennsylvania, United States
North Texas VA Medical Center
🇺🇸Dallas, Texas, United States
Kelsey Seybold Clnic
🇺🇸Houston, Texas, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Swedish Cancer Inst.
🇺🇸Seattle, Washington, United States
CEDOES - Diagnóstico e Pesquisa
🇧🇷Vitoria, Espírito Santo, Brazil
Hospital do Cancer de Pernambuco - HCP
🇧🇷Recife, Pernambuco, Brazil
Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital de Cancer de Barretos
🇧🇷Barretos, São Paulo, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP
🇧🇷Sao Paulo, São Paulo, Brazil
Clinicas Oncologicas Integradas - COI
🇧🇷Rio De Janeiro, Brazil
Juravinski Hospital
🇨🇦Hamilton, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
McGill University Health Centre - Glen Site
🇨🇦Montreal, Quebec, Canada
Baoji Central Hospital
🇨🇳Baoji City, China
Beijing Cancer Hospital
🇨🇳Beijing, China
The First Hospital of Jilin University
🇨🇳Changchun City, China
Hunan Cancer Hospital
🇨🇳Changsha CITY, China
Mengchao Hepatobiliary Hospital Of Fujian Medical University
🇨🇳Fuzhou City, China
Nanfang Hospital, Southern Medical University
🇨🇳Guangzhou, China
Sun yat-sen University Cancer Center
🇨🇳Guangzhou, China
The First Affiliated Hospital of College of Medicine, Zhejiang University
🇨🇳Hangzhou, China
Zhejiang Provincial People?s Hospital
🇨🇳Hangzhou, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
The Second Affiliated Hospital of Anhui Medical University
🇨🇳Hefei City, China
Anhui Provincial Hospital
🇨🇳Hefei, China
Lishui Central Hospital
🇨🇳Lishui City, China
Zhongshan Hospital Fudan Unvierstiy
🇨🇳Shanghai City, China
Renji Hospital Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai City, China
Shengjing Hospital of China Medical University
🇨🇳ShenYang, China
Polyclinique Internationale Sainte Anne- Marie (PISAM)
🇨🇮Abidjan, Côte D'Ivoire
Centre National d'Oncologie Médicale et de Radiothérapie Alassane Ouattara (CNRAO)
🇨🇮Abidjan, Côte D'Ivoire
CHU CAEN - Hôpital de la Côte de Nacre
🇫🇷Caen Cedex, France
CHRU de Lille - Hopital Claude Huriez
🇫🇷Lille, France
Hopital Dupuytren
🇫🇷Limoges, France
Fondation Hopital Saint Joseph
🇫🇷Marseille, France
Hopital Hotel Dieu Et Hme
🇫🇷Nantes, France
APHP - Hopital Saint Antoine
🇫🇷Paris, France
Hopital Robert Debre
🇫🇷Reims, France
Centre Hospitalier Valence
🇫🇷Valence, France
Hopitaux de Brabois - Gastro-Entereologie
🇫🇷Vandoeuvre-les-nancy, France
Hopital Paul Brousse
🇫🇷Villejuif, France
Klinikum Esslingen
🇩🇪Esslingen, Germany
Universitätsklinikum Magdeburg Klinik für Gastroenterologie und Hepatologie
🇩🇪Magdeburg, Germany
Uniklinik Mainz
🇩🇪Mainz, Germany
Universität Tübingen
🇩🇪Tübingen, Germany
KBTH
🇬🇭Accra, Ghana
Sweden Ghana Medical Center
🇬🇭Accra, Ghana
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Prince of Wales Hosp
🇭🇰Shatin, Hong Kong
A.O. S. Orsola Malpighi
🇮🇹Bologna, Emilia-Romagna, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Lazio, Italy
Az. Osp. Uni Ria San Martino
🇮🇹Genova, Liguria, Italy
IRCCS Istituto Clinico Humanitas
🇮🇹Rozzano, Lombardia, Italy
Az. Osp. G. Panico
🇮🇹Tricase, Puglia, Italy
Kanazawa University Hospital
🇯🇵Ishikawa, Japan
Iwate Medical University Hospital
🇯🇵Iwate, Japan
Toranomon Branch Hospital
🇯🇵Kanagawa, Japan
Toranomon Hospital
🇯🇵Tokyo, Japan
University of Nairobi - Institute of Tropical and Infectious Diseases
🇰🇪Nairobi, Kenya
Kurume University Hospital
🇯🇵Fukuoka, Japan
Hiroshima University Hospital
🇯🇵Hiroshima, Japan
Sapporo Kosei General Hospital
🇯🇵Hokkaido, Japan
Hokkaido University Hospital
🇯🇵Hokkaido, Japan
Kitasato University Hospital
🇯🇵Kanagawa, Japan
University Hospital Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Osaka University Hospital
🇯🇵Osaka, Japan
Kindai University Hospital
🇯🇵Osaka, Japan
Jichi Medical University Hospital
🇯🇵Tochigi, Japan
Japanese Red Cross Musashino Hospital
🇯🇵Tokyo, Japan
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
CHA Bundang Medical Center
🇰🇷Gyeonggi-do, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Jeollanam-do, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
OncoMed
🇲🇽Ciudad de México, Mexico CITY (federal District), Mexico
Centro Medico Nacional Siglo Xxi - Imss
🇲🇽Mexico City, Mexico CITY (federal District), Mexico
Instituto Nacional de Ciencias Médicas Y de Nutricion Salvador Zubirán
🇲🇽Mexico DF, Mexico CITY (federal District), Mexico
Centro de Investigacion Clinica de Oaxaca
🇲🇽Oaxaca de Juárez, Oaxaca, Mexico
Auckland City Hospital
🇳🇿Auckland, New Zealand
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Wellington Hospital
🇳🇿Wellington, New Zealand
Jos University Teaching Hospital
🇳🇬JOS, Nigeria
Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii
🇵🇱Gdansk, Poland
ID Clinic
🇵🇱Myslowice, Poland
NIO im Marii Sklodowskiej-Curie
🇵🇱Warszawa, Poland
PanOncology Trials
🇵🇷San Juan, Puerto Rico
National Cancer Centre
🇸🇬Singapore, Singapore
Charlotte Maxeke Johannesburg Academic Hospital
🇿🇦Johannesburg, South Africa
Limpopo Cancer Research Institute
🇿🇦Polokwane, South Africa
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Asturias, Spain
Clinica Universitaria de Navarra
🇪🇸Pamplona/iruña, Navarra, Spain