A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC) (IMbrave152)
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.
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.
Tiragolumab: Tiragolumab will be administered by IV infusion at a fixed dose of 600 mg on Day 1 of each 21-day cycle.
Placebo: Placebo matching tiragolumab will be administered by IV infusion on Day 1 of each 21-day cycle.
Study 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 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Investigator-assessed Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) — From randomization to the first occurrence of disease progression (PD) or death from any cause, whichever occurs first (up to approximately 21 months)
Overall Survival (OS) — From randomization to death from any cause (up to approximately 36 months)
Trial sites (171)
Facility
City
Region
Status
Genesis Cancer Center
Hot Springs
Arkansas
UCSF Fresno at Community Cancer Institute
Clovis
California
City of Hope Cancer Center
Duarte
California
University of California San Diego Moores Cancer Center
La Jolla
California
University of Southern California
Los Angeles
California
Stanford Cancer Center
Palo Alto
California
Va Palo Alto Health Care System
Palo Alto
California
UCLA Cancer Center
Santa Monica
California
Hartford Healthcare Cancer Institute at Hartford Hospital
Hartford
Connecticut
MedStar Washington Hosp Center
Washington D.C.
District of Columbia
Florida Cancer Specialists - Fort Myers (Broadway)
Fort Myers
Florida
Miami VA Healthcare System
Miami
Florida
Florida Cancer Specialist, North Region
St. Petersburg
Florida
University of Illinois
Chicago
Illinois
Norton Cancer Institute - Audubon
Louisville
Kentucky
Ochsner Cancer Inst.
New Orleans
Louisiana
Mercy Medical Center
Baltimore
Maryland
Henry Ford Health System
Detroit
Michigan
Cancer & Hematology Centers of Western Michigan
Grand Rapids
Michigan
Mayo Clinic Rochester
Rochester
Minnesota
Minnesota Oncology Hematology Woodbury
Woodbury
Minnesota
Washington Uni School of Medicine
St Louis
Missouri
NYU Langone
New York
New York
Icahn School of Medicine at Mount Sinai
New York
New York
Columbia University
New York
New York
Montefiore Medical Center
The Bronx
New York
James J Peters VA Hospital / Mental Illness Research Education and Clinic Center
The Bronx
New York
University of North Carolina at Chapel Hill
Chapel Hill
North Carolina
Thomas Jefferson Uni
Philadelphia
Pennsylvania
North Texas VA Medical Center
Dallas
Texas
Kelsey Seybold Clnic
Houston
Texas
Virginia Mason Medical Center
Seattle
Washington
Swedish Cancer Inst.
Seattle
Washington
Univ of Wisconsin-Madison
Madison
Wisconsin
Cliniques Universitaires St-Luc
Brussels
Belgium
UZ Antwerpen
Edegem
Belgium
AZ Delta (Campus Rumbeke)
Roeselare
Belgium
CEDOES - Diagnóstico e Pesquisa
Vitória
Espírito Santo
Oncoclínicas do Brasil - BELO HORIZONTE
Belo Horizonte
Minas Gerais
Hospital do Cancer de Pernambuco - HCP
Recife
Pernambuco
+ 131 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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