Clinical trial NCT05904886: A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (IMbrave152)
Official title: A 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 type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Carcinoma, Hepatocellular
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Chugai Pharmaceutical
First posted: 2023-06-15
Enrollment: 650
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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
* 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 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.

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