A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC) (IMbrave152)
SKYSCRAPER-14
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
2 other identifiers
interventional
687
27 countries
171
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 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 hepatocellular-carcinoma
Started Sep 2023
Shorter than P25 for phase_3 hepatocellular-carcinoma
171 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 23, 2023
CompletedFirst Posted
Study publicly available on registry
June 15, 2023
CompletedStudy Start
First participant enrolled
September 14, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 8, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2026
ExpectedDecember 31, 2025
December 1, 2025
1.6 years
May 23, 2023
December 30, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
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)
Secondary Outcomes (14)
Investigator-assessed Confirmed Objective Response Rate (ORR) According to RECIST v1.1
From randomization up to approximately 21 months
Investigator-assessed Duration of Response (DOR) According to RECIST v1.1
From the first occurrence of a documented confirmed objective response to the first occurrence of PD or death from any cause, whichever occurs first (up to approximately 21 months)
Investigator-assessed PFS Rate According to RECIST v1.1 at 6 and 12 Months
Month 6, Month 12
OS Rate at 1 and 2 Years
Year 1, Year 2
Investigator-assessed PFS According to HCC mRECIST
From randomization to the first occurrence of PD or death from any cause, whichever occurs first (up to approximately 21 months)
- +9 more secondary outcomes
Study Arms (2)
Atezolizumab + Bevacizumab + Tiragolumab
EXPERIMENTALAtezolizumab 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 COMPARATORAtezolizumab, bevacizumab plus placebo will be administered Q3W until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Interventions
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 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 will be administered by IV infusion at a fixed dose of 600 mg on Day 1 of each 21-day cycle.
Placebo matching tiragolumab will be administered by IV infusion on Day 1 of each 21-day cycle.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Hoffmann-La Rochelead
- Chugai Pharmaceuticalcollaborator
Study Sites (171)
Genesis Cancer Center
Hot Springs, Arkansas, 71913, United States
UCSF Fresno at Community Cancer Institute
Clovis, California, 93611, United States
City of Hope Cancer Center
Duarte, California, 91010, United States
University of California San Diego Moores Cancer Center
La Jolla, California, 92037, United States
University of Southern California
Los Angeles, California, 90033, United States
Stanford Cancer Center
Palo Alto, California, 94304, United States
Va Palo Alto Health Care System
Palo Alto, California, 94304, United States
UCLA Cancer Center
Santa Monica, California, 90404, United States
Hartford Healthcare Cancer Institute at Hartford Hospital
Hartford, Connecticut, 06106, United States
MedStar Washington Hosp Center
Washington D.C., District of Columbia, 20010, United States
Florida Cancer Specialists - Fort Myers (Broadway)
Fort Myers, Florida, 33901, United States
Miami VA Healthcare System
Miami, Florida, 33125, United States
Florida Cancer Specialist, North Region
St. Petersburg, Florida, 33705, United States
University of Illinois
Chicago, Illinois, 60612, United States
Norton Cancer Institute - Audubon
Louisville, Kentucky, 40217, United States
Ochsner Cancer Inst.
New Orleans, Louisiana, 70121, United States
Mercy Medical Center
Baltimore, Maryland, 21202, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
Cancer & Hematology Centers of Western Michigan
Grand Rapids, Michigan, 49503, United States
Mayo Clinic Rochester
Rochester, Minnesota, 55905, United States
Minnesota Oncology Hematology Woodbury
Woodbury, Minnesota, 55125, United States
Washington Uni School of Medicine
St Louis, Missouri, 63110, United States
NYU Langone
New York, New York, 10016, United States
Icahn School of Medicine at Mount Sinai
New York, New York, 10029, United States
Columbia University
New York, New York, 10032-3725, United States
Montefiore Medical Center
The Bronx, New York, 10461, United States
James J Peters VA Hospital / Mental Illness Research Education and Clinic Center
The Bronx, New York, 10468, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27514, United States
Thomas Jefferson Uni
Philadelphia, Pennsylvania, 19107, United States
North Texas VA Medical Center
Dallas, Texas, 75216, United States
Kelsey Seybold Clnic
Houston, Texas, 77005, United States
Virginia Mason Medical Center
Seattle, Washington, 98101, United States
Swedish Cancer Inst.
Seattle, Washington, 98104, United States
Univ of Wisconsin-Madison
Madison, Wisconsin, 53792, United States
Cliniques Universitaires St-Luc
Brussels, 1200, Belgium
UZ Antwerpen
Edegem, 2650, Belgium
AZ Delta (Campus Rumbeke)
Roeselare, 8800, Belgium
CEDOES - Diagnóstico e Pesquisa
Vitória, Espírito Santo, 29055-450, Brazil
Oncoclínicas do Brasil - BELO HORIZONTE
Belo Horizonte, Minas Gerais, 30170-080, Brazil
Hospital do Cancer de Pernambuco - HCP
Recife, Pernambuco, 50040-000, Brazil
Santa Casa de Misericordia de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90020-090, Brazil
Hospital Sao Lucas - PUCRS
Porto Alegre, Rio Grande do Sul, 90610-000, Brazil
Hospital de Cancer de Barretos
Barretos, São Paulo, 14784-400, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP
São Paulo, São Paulo, 01246-000, Brazil
Clinicas Oncologicas Integradas - COI
Rio de Janeiro, 22290-160, Brazil
Juravinski Hospital
Hamilton, Ontario, L8V 1C3, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5, Canada
Jewish General Hospital
Montreal, Quebec, H3T 1E2, Canada
McGill University Health Centre - Glen Site
Montreal, Quebec, H4A 3J1, Canada
Baoji Central Hospital
Baoji, 721008, China
Beijing Cancer Hospital
Beijing, 100142, China
The First Hospital of Jilin University
Changchun, 130021, China
Peoples Hospital of Hunan Province
Changsha, 410007, China
Hunan Cancer Hospital
Changsha, 410013, China
West China Hospital - Sichuan University
Chengdu, 610047, China
Mengchao Hepatobiliary Hospital Of Fujian Medical University
Fuzhou, 350025, China
Nanfang Hospital, Southern Medical University
Guangzhou, 510515, China
Sun yat-sen University Cancer Center
Guangzhou, China
The First Affiliated Hospital of College of Medicine, Zhejiang University
Hangzhou, 310003, China
Zhejiang Provincial People?s Hospital
Hangzhou, 310014, China
Harbin Medical University Cancer Hospital
Harbin, 150081, China
Anhui Provincial Hospital
Hefei, 230001, China
The Second Affiliated Hospital of Anhui Medical University
Hefei, 230601, China
Lishui Central Hospital
Lishui, 323000, China
Zhongshan Hospital Fudan Unvierstiy
Shanghai, 200032, China
Renji Hospital Shanghai Jiaotong University School of Medicine
Shanghai, 200127, China
Shengjing Hospital of China Medical University
Shenyang, 110004, China
Tianjin Cancer Hospital
Tianjin, 300060, China
Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan, 430030, China
First Affiliated Hospital of Medical College of Xi'an Jiaotong University
Xi'an, 710061, China
Xi'an Inernational Medical Center Hospital
Xi'an, 710119, China
Polyclinique Internationale Sainte Anne- Marie (PISAM)
Abidjan, BP 1463 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, 14033, France
CHRU de Lille - Hopital Claude Huriez
Lille, 59037, France
Hopital Dupuytren
Limoges, 87042, France
Fondation Hopital Saint Joseph
Marseille, 13285, France
Hopital Hotel Dieu Et Hme
Nantes, 44093, France
APHP - Hopital Saint Antoine
Paris, 75571, France
Hopital Robert Debre
Reims, 51092, France
Centre Hospitalier Valence
Valence, 26953, France
Hopitaux de Brabois - Gastro-Entereologie
Vandœuvre-lès-Nancy, 54511, France
Hopital Paul Brousse
Villejuif, 94804, France
Klinikum Esslingen
Esslingen am Neckar, 73730, Germany
Universitätsklinikum Magdeburg Klinik für Gastroenterologie und Hepatologie
Magdeburg, 39120, Germany
Uniklinik Mainz
Mainz, 55131, Germany
Universität Tübingen
Tübingen, 72076, Germany
KBTH
Accra, 0000, Ghana
Sweden 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, 40138, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Rome, Lazio, 00168, Italy
Az. Osp. Uni Ria San Martino
Genoa, Liguria, 16132, Italy
IRCCS Istituto Clinico Humanitas
Rozzano, Lombardy, 20089, Italy
A.O.U. Policlinico Paolo Giaccone
Palermo, Sicily, 90127, Italy
A.O.U.I. Verona-Ospedale Policlinico G.B. Rossi Borgo Roma
Verona, Veneto, 37134, Italy
Fujita Health University Hospital
Aichi, 470-1192, Japan
Chiba University Hospital
Chiba, 260-8677, Japan
National Cancer Center Hospital East
Chiba, 277-8577, Japan
Ehime Prefectural Central Hospital
Ehime, 790-0024, Japan
Kurume University Hospital
Fukuoka, 830-0011, Japan
Hiroshima University Hospital
Hiroshima, 734-8551, Japan
Sapporo Kosei General Hospital
Hokkaido, 060-0033, Japan
Hokkaido University Hospital
Hokkaido, 060-8648, Japan
Kanazawa University Hospital
Ishikawa, 920-8641, Japan
Toranomon Branch Hospital
Kanagawa, 213-8587, Japan
Kanagawa Cancer Center
Kanagawa, 241-8515, Japan
Kitasato University Hospital
Kanagawa, 252-0375, Japan
University Hospital Kyoto Prefectural University of Medicine
Kyoto, 602-8566, Japan
Kyoto University Hospital
Kyoto, 606-8507, Japan
Iwate Medical University Hospital
Numakunai, 028-3695, Japan
The University of Osaka Hospital
Osaka, 565-0871, Japan
Kindai University Hospital
Osaka, 589-8511, Japan
Jichi Medical University Hospital
Tochigi, 329-0498, Japan
Toranomon Hospital
Tokyo, 105-8470, Japan
Japanese Red Cross Musashino Hospital
Tokyo, 180-8610, Japan
University of Nairobi - Institute of Tropical and Infectious Diseases
Nairobi, Kenya
OncoMed
Mexico City, Mexico CITY (federal District), 03100, Mexico
Centro Medico Nacional Siglo Xxi - Imss
Mexico City, Mexico CITY (federal District), 06720, Mexico
Instituto Nacional de Ciencias Médicas Y de Nutricion Salvador Zubirán
Mexico City, Mexico CITY (federal District), 14000, Mexico
Centro de Investigacion Clinica de Oaxaca
Oaxaca City, Oaxaca, 68020, Mexico
Auckland City Hospital
Auckland, 1023, New Zealand
Christchurch Hospital
Christchurch, 8011, New Zealand
Wellington Hospital
Wellington, 6021, New Zealand
Jos University Teaching Hospital
Jos, 930232, Nigeria
Lagos University Teaching Hospital Lagos (LUTH), Lagos State
Lagos, Nigeria
ID Clinic
Mysłowice, 41-400, Poland
NIO im Marii Sklodowskiej-Curie
Warsaw, 02-034, Poland
PanOncology Trials
San Juan, 00935, Puerto Rico
National Cancer Centre
Singapore, 168583, Singapore
Charlotte Maxeke Johannesburg Academic Hospital
Johannesburg, 2193, South Africa
Limpopo Cancer Research Institute
Polokwane, 0700, South Africa
National Cancer Center
Goyang-si, 10408, South Korea
CHA Bundang Medical Center
Gyeonggi-do, 13496, South Korea
Chonnam National University Hwasun Hospital
Jeollanam-do, 58128, South Korea
Severance Hospital, Yonsei University Health System
Seoul, 003-722, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Ulsan University Hosiptal
Ulsan, 44033, South Korea
Hospital de Navarra
Navarra, Navarre, 31008, Spain
Clinica Universitaria de Navarra
Pamplona/iruña, Navarre, 31008, Spain
Hospital Universitario Central de Asturias
Oviedo, Principality of Asturias, 33011, Spain
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
Hospital Duran i Reynals
Barcelona, 08907, Spain
Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico
Jaén, 23007, Spain
Hospital General Universitario Gregorio Marañon
Madrid, 28007, Spain
Clinica Universitaria de Navarra de Madrid;Servicio de Hepatologia
Madrid, 28027, Spain
Hospital Clinico San Carlos
Madrid, 28040, Spain
Hospital Universitario Puerta de Hierro
Madrid, 28222, Spain
Hospital Clinico de Valencia
Valencia, 46010, Spain
China Medical University Hospital
Taichung, 404, Taiwan
National Cheng Kung University Hospital
Tainan, 00704, Taiwan
Chi-Mei Medical Centre
Tainan, 710, Taiwan
National Taiwan Uni Hospital
Taipei, 100, Taiwan
Chang Gung Medical Foundation - Linkou
Taoyuan District, 333, Taiwan
Chulalongkorn Hospital
Bangkok, 10330, Thailand
Ramathibodi Hospital
Bangkok, 10400, Thailand
Maharaj Nakorn Chiang Mai Hospital
Chiang Mai, 50200, Thailand
Khon Kaen Uni
Khon Kaen, 40002, Thailand
Adana Baskent University Medical Faculty
Adana, 01220, Turkey (Türkiye)
Ankara Bilkent City Hospital
Ankara, 06490, Turkey (Türkiye)
Gazi Uni Medical Faculty Hospital
Ankara, 06500, Turkey (Türkiye)
Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
Edirne, 22030, Turkey (Türkiye)
?zmir Medical Point
Kar?iyaka, 35575, Turkey (Türkiye)
Uganda Cancer Institute
Kampala, Uganda
Western General Hospital
Edinburgh, EH4 2XU, United Kingdom
Royal Free Hospital
London, NW3 2QG, United Kingdom
Hammersmith Hospital
London, W12 0HS, United Kingdom
Related Publications (1)
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.
PMID: 38861301DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- The study has been unblinded as of amendment version 5.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 23, 2023
First Posted
June 15, 2023
Study Start
September 14, 2023
Primary Completion
May 8, 2025
Study Completion (Estimated)
September 1, 2026
Last Updated
December 31, 2025
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing