A Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
IMbrave150
A Phase III, Open-Label, Randomized Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
2 other identifiers
interventional
558
17 countries
119
Brief Summary
This study will evaluate the efficacy and safety of atezolizumab in combination with bevacizumab compared with sorafenib in participants with locally advanced or metastatic Hepatocellular Carcinoma (HCC) who have received no prior systemic treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2018
Longer than P75 for phase_3
119 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
January 31, 2018
CompletedFirst Posted
Study publicly available on registry
February 15, 2018
CompletedStudy Start
First participant enrolled
March 15, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2020
CompletedResults Posted
Study results publicly available
November 5, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
November 17, 2022
CompletedOctober 23, 2023
September 1, 2023
2.5 years
January 31, 2018
August 16, 2021
October 5, 2023
Conditions
Outcome Measures
Primary Outcomes (4)
Overall Survival (OS) in the Global Population
OS was defined as the time from randomization to death from any cause.
From randomization to death from any cause up to the clinical cut off date (CCOD) of 29Aug2019 (up to approximately 18 months) and 31Aug2020 (up to approximately 30 months)
Progression Free Survival by Independent Review Facility-Assessment (PFS-IRF) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the Global Population
PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause whichever occurs first as determined by an IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).
Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)
Overall Survival (OS) in the China Population
OS was defined as the time from randomization to death from any cause.
From randomization to death from any cause up to the clinical cut off date (CCOD) of 29Aug2019 (up to approximately 18 months) and 31Aug2020 (up to approximately 30 months)
PFS-IRF Per RECIST v1.1 in the China Population
PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause whichever occurs first as determined by an IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).
Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)
Secondary Outcomes (35)
Objective Response Rate by IRF-Assessment (ORR-IRF) Per RECIST v1.1 in the Global Population
Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)
Objective Response Rate by IRF-Assessment (ORR-IRF) Per Hepatocellular Carcinoma (HCC) Modified RECIST (mRECIST) in the Global Population
Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)
ORR by Investigator-Assessment (ORR-INV) Per RECIST v1.1 in the Global Population
Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)
Duration of Response by IRF-Assessment (DOR-IRF) Per RECIST v1.1 in the Global Population
Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)
Duration of Response by IRF Assessment (DOR-IRF) Per HCC mRECIST in the Global Population
Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)
- +30 more secondary outcomes
Study Arms (2)
Atezolizumab + Bevacizumab
EXPERIMENTALParticipants will receive Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator
Sorafenib
ACTIVE COMPARATORParticipants will receive Sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator
Interventions
Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21 day cycle
Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21 day cycle
Sorafenib will be administered by mouth, 400 mg twice per day, on days 1-21 of each 21-day cycle
Eligibility Criteria
You may qualify if:
- Locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC)
- No prior systemic therapy for HCC. Previous use of herbal therapies/traditional Chinese medicines with anti-cancer activity included in the label is allowed, provided that these medications are discontinued prior to randomization.
- At least one measurable untreated lesion
- ECOG Performance Status of 0 or 1
- Adequate hematologic and end-organ function
- For women of childbearing potential: agreement to remain abstinent
- For men: agreement to remain abstinent
- Child-Pugh class A
You may not qualify if:
- History of leptomeningeal disease
- 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 scan
- Known active tuberculosis
- 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
- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 5 months after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, or 1 month after the last dose of sorafenib
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding
- A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment.
- Moderate or severe ascites
- History of hepatic encephalopathy
- Co-infection of HBV and HCV
- Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- Uncontrolled tumor-related pain
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (119)
St. Josephs Hospital and Medical Center
Phoenix, Arizona, 85260, United States
City of Hope
Duarte, California, 91010, United States
Uni of California - San Diego; Cancer Center & Dept of Medicine
La Jolla, California, 92093, United States
Kaiser Permanente Northern California
Novato, California, 94589, United States
University of California Irvine Medical Center
Orange, California, 92868, United States
Kaiser Permanente Sacramento Medical Center
Sacramento, California, 95825, United States
California Pacific Medical Center
San Francisco, California, 94115, United States
Kaiser Permanente - San Francisco Medical Center
San Francisco, California, 94118, United States
University of California Los Angeles
Santa Monica, California, 90404, United States
Kaiser Permanente - Walnut Creek
Walnut Creek, California, 94596, United States
Banner MD Anderson Cancer Center
Greeley, Colorado, 85234, United States
Georgetown University
Washington D.C., District of Columbia, 20007, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
Washington University; Wash Uni. Sch. Of Med
St Louis, Missouri, 63110, United States
University of New Mexico Comprehensive Cancer Center
Albuquerque, New Mexico, 87102, United States
Laura and ISAAC Perlmutter Cancer Center at NYU Langone.
New York, New York, 10016, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
M.D Anderson Cancer Center; Uni of Texas At Houston
Houston, Texas, 77030, United States
Swedish Cancer Inst.
Seattle, Washington, 98104, United States
Bankstown-Lidcombe Hospital
Bankstown, New South Wales, 2200, Australia
St George Hospital
Kogarah, New South Wales, 2217, Australia
The Queen Elizabeth Hospital
Woodville, South Australia, 5011, Australia
Sunshine Hospital
St Albans, Victoria, 3021, Australia
Ottawa Hospital Research Institute
Ottawa, Ontario, K1Y 4E9, Canada
Centre hospitalier de l'Universite de Montreal (CHUM)
Montreal, Quebec, H2X 0A9, Canada
Jewish General Hospital
Montreal, Quebec, H3T 1E2, Canada
McGill University Health Centre - Glen Site
Montreal, Quebec, H4A 3J1, Canada
Peking Union Medical College Hospital
Beijing, 100032, China
Beijing Friendship Hospital
Beijing, 100050, China
Beijing Cancer Hospital
Beijing, 100142, China
the First Hospital of Jilin University
Changchun, 130021, China
Jilin Cancer Hospital
Changchun, 132013, China
Hunan Cancer Hospital
Changsha, 410013, China
The First People's Hospital of Foshan; Local Ethic Committee
Foshan, 510000, China
The 900th Hospital of PLA joint service support force
Fuzhou, 110016, China
Nanfang Hospital, Southern Medical University
Guangzhou, 510515, China
Sun Yet-sen University Cancer Center
Guangzhou, 510663, China
The First Affiliated Hospital of College of Medicine, Zhejiang University
Hangzhou, 310003, China
Sir Run Run Shaw Hospital
Hangzhou, 310018, China
Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department
Hangzhou, 310022, China
Harbin Medical University Cancer Hospital
Harbin, 150081, China
The First Affiliated Hospital of Anhui Medical University
Hefei, 230022, China
Anhui Province Cancer Hospital
Hefei, 230031, China
General Hospital of Jinan Military Command of PLA
Jinan, 250031, China
The 81st Hospital of P.L.A.
Nanjing, 210002, China
Zhongshan Hospital Fudan University
Shanghai, 200032, China
Fudan University Shanghai Cancer Center
Shanghai, 200120, China
Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech
Wuhan, 430030, China
Masarykuv onkologicky ustav
Brno, 656 53, Czechia
Fakultni nemocnice Olomouc; Onkologicka klinika
Olomouc, 779 00, Czechia
Hopital Claude Huriez;Gastro Enterologie
Lille, 59037, France
Hopital De La Croix Rousse; Hepatologie Gastro Enterologie
Lyon, 69317, France
Hopital Timone Adultes; Gastro Enterologie
Marseille, 13385, France
Hopital Saint-Eloi; Hepatologie-Gastro-Enterologie
Montpellier, 34295, France
Hopital Hotel Dieu Et Hme; Hepatologie Gastro Enterologie
Nantes, 44093, France
CHU Nice - HĂ´pital de l'Archet 2; service Hepato gastro enterologie
Nice, 06202, France
Hopital Charles Nicolle; Gastroenterologie
Rouen, 76031, France
Hopital Hautepierre; Gastro Enterologie
Strasbourg, 67098, France
Hôpital d'Adultes; Service hépato-gastro-entérologie
Vandœuvre-lès-Nancy, 54511, France
Institut Gustave Roussy; Gastro-Enterologie
Villejuif, 94805, France
Campus Virchow-Klinikum Charité Centrum 13; Medizinische Klinik; Abt.Hepatologie u.Gastroenterologie
Berlin, 13353, Germany
Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik I
Frankfurt, 60590, Germany
Universitaetsklinikum Hamburg-Eppendorf; I. Medizinische Klinik - Gastroenterologie
Hamburg, 20246, Germany
Med. Hochschule Hannover; Gastroenterologie
Hanover, 30625, Germany
Universitätsklinikum Leipzig Medizinische Klinik II Gastroenterolog. u. Hepatolog.
Leipzig, 04103, Germany
Uniklinik Mainz; I. Medizinische Klinik
Mainz, 55131, Germany
Klinikum der Uni Regensburg; Klinik f.Innere Medizin I Abt. Hämatologie und Internistische Onkologie
Regensburg, 93053, Germany
Queen Mary Hospital; Dept. Of Haematology & Oncology
Hong Kong, Hong Kong
Prince of Wales Hosp; Dept. Of Clinical Onc
Shatin, Hong Kong
Az. Osp. Rummo; Oncologia Medica
Benevento, Campania, 82100, Italy
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
Meldola, Emilia-Romagna, 47014, Italy
Az. Osp. S. Luigi Gonzaga; Divisione Di Oncologia Medica
Orbassano, Piedmont, 10043, Italy
A.O.U. Cagliari-P.O. Monserrato;U.O. Oncologia
Cagliari, Sardinia, 09100, Italy
Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria ? Polo Oncologico
Pisa, Tuscany, 56126, Italy
IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima
Padua, Veneto, 35128, Italy
Chiba University Hospital
Chiba, 260-8677, Japan
National Cancer Center Hospital East
Chiba, 277-8577, Japan
Kurume University Hospital
Fukuoka, 830-0011, Japan
Sapporo Kosei Genaral Hospital
Hokkaido, 060-0033, Japan
Hokkaido University Hospital
Hokkaido, 060-8648, Japan
Kanazawa University Hospital
Ishikawa, 920-8641, Japan
Kitasato University Hospital
Kanagawa, 252-0375, Japan
Kumamoto University Hospital
Kumamoto, 860-8556, Japan
Osaka Metropolitan University Hospital
Osaka, 545-8586, Japan
Kindai University Hospital
Osaka, 589-8511, Japan
Saga-ken Medical Centre Koseikan
Saga, 840-8571, Japan
Shizuoka Cancer Center
Shizuoka, 411-8777, Japan
Japanese Red Cross Musashino Hospital
Tokyo, 180-8610, Japan
Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii
Gdansk, 80-219, Poland
ID Clinic
Mysłowice, 41-400, Poland
SP ZOZ MSWiA z WARMINSKO-MAZURSKIM CENTRUM ONKOLOGII; CLINICAL ONCOLOGY, CLINICAL IMMUNOLOGY
Olsztyn, 10-228, Poland
Narodowy Instytut Onkologii im. Marii Sk?odowskiej-Curie - Pa?stwowy Instytut Badawczy
Warsaw, 02-781, Poland
Dolno?l?skie Centrum Onkologii; Oddzia? Onkologii Klinicznej i Chemioterapii
Wroc?aw, 53-413, Poland
FSBI "National Medical Research Center of Oncology N.N. Blokhin?; Clinical Biotechnologies
Moscow, Moscow Oblast, 115478, Russia
GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology)
Saint Petersburg, Sankt-Peterburg, 197758, Russia
National Cancer Centre
Singapore, 169610, Singapore
Tan Tock Seng Hospital; Oncology
Singapore, 308433, Singapore
Chonnam National University Hwasun Hospital
Jeollanam-do, 58128, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Severance Hospital, Yonsei University Health System
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Ulsan University Hosiptal
Ulsan, 44033, South Korea
Hospital Universitari Vall d'Hebron; Oncology
Barcelona, 08035, Spain
Hospital Clinico San Carlos; Servicio de Oncologia
Madrid, 28040, Spain
Hospital Universitario La Paz; Servicio de Oncologia
Madrid, 28046, Spain
Centro Integral Oncologico Clara Campal; Servicio de OncologĂa
Madrid, 28050, Spain
Hospital Universitario Miguel Servet; Servicio de Oncologia Medica
Zaragoza, 50009, Spain
National Cheng Kung University Hospital; Oncology
Tainan, 00704, Taiwan
Chi-Mei Medical Centre; Hematology & Oncology
Tainan, 710, Taiwan
Veterans General Hospital; Cancer Center
Taipei, 00112, Taiwan
National Taiwan Uni Hospital; Dept of Oncology
Taipei, 100, Taiwan
Chang Gung Memorial Hospital-Linkou; Dept of Oncology
Taoyuan, 333, Taiwan
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN, United Kingdom
Royal Free Hospital; Dept of Oncology
London, NW3 2QG, United Kingdom
King'S College Hospital
London, SE5 9RS, United Kingdom
Christie Hospital Nhs Trust; Medical Oncology
Manchester, M2O 4BX, United Kingdom
Related Publications (8)
Xu XQ, Li WM, Shi LC, Wang H, Li S, Huang C, You H, Jia JD, He YW, Kong YY. Impact of temporary atezolizumab and bevacizumab interruption on survival in advanced HCC: an IMbrave150 analysis. Oncologist. 2025 Sep 1;30(9):oyaf269. doi: 10.1093/oncolo/oyaf269.
PMID: 40891895DERIVEDKaseb AO, Guan Y, Gok Yavuz B, Abbas AR, Lu S, Hasanov E, Toh HC, Verret W, Wang Y. Serum IGF-1 Scores and Clinical Outcomes in the Phase III IMbrave150 Study of Atezolizumab Plus Bevacizumab versus Sorafenib in Patients with Unresectable Hepatocellular Carcinoma. J Hepatocell Carcinoma. 2022 Oct 11;9:1065-1079. doi: 10.2147/JHC.S369951. eCollection 2022.
PMID: 36254201DERIVEDLi Y, Liang X, Li H, Chen X. Atezolizumab plus bevacizumab versus nivolumab as first-line treatment for advanced or unresectable hepatocellular carcinoma: A cost-effectiveness analysis. Cancer. 2022 Nov 15;128(22):3995-4003. doi: 10.1002/cncr.34457. Epub 2022 Sep 16.
PMID: 36111952DERIVEDCheng AL, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Lim HY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Ma N, Nicholas A, Wang Y, Li L, Zhu AX, Finn RS. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022 Apr;76(4):862-873. doi: 10.1016/j.jhep.2021.11.030. Epub 2021 Dec 11.
PMID: 34902530DERIVEDSalem R, Li D, Sommer N, Hernandez S, Verret W, Ding B, Lencioni R. Characterization of response to atezolizumab + bevacizumab versus sorafenib for hepatocellular carcinoma: Results from the IMbrave150 trial. Cancer Med. 2021 Aug;10(16):5437-5447. doi: 10.1002/cam4.4090. Epub 2021 Jun 29.
PMID: 34189869DERIVEDGalle PR, Finn RS, Qin S, Ikeda M, Zhu AX, Kim TY, Kudo M, Breder V, Merle P, Kaseb A, Li D, Mulla S, Verret W, Xu DZ, Hernandez S, Ding B, Liu J, Huang C, Lim HY, Cheng AL, Ducreux M. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Jul;22(7):991-1001. doi: 10.1016/S1470-2045(21)00151-0. Epub 2021 May 27.
PMID: 34051880DERIVEDWen F, Zheng H, Zhang P, Liao W, Zhou K, Li Q. Atezolizumab and bevacizumab combination compared with sorafenib as the first-line systemic treatment for patients with unresectable hepatocellular carcinoma: A cost-effectiveness analysis in China and the United states. Liver Int. 2021 May;41(5):1097-1104. doi: 10.1111/liv.14795. Epub 2021 Feb 8.
PMID: 33556230DERIVEDFinn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.
PMID: 32402160DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Hoffmann-La Roche
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 31, 2018
First Posted
February 15, 2018
Study Start
March 15, 2018
Primary Completion
August 31, 2020
Study Completion
November 17, 2022
Last Updated
October 23, 2023
Results First Posted
November 5, 2021
Record last verified: 2023-09
Data Sharing
- IPD Sharing
- Will share
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).