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

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.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Hepatocellular
• Intervention / Treatment: Drug: Atezolizumab; Drug: Bevacizumab; Drug: Sorafenib

Detailed Description

The participants will be randomized in a 2:1 ratio to one of the two treatment arms: Arm A (experimental arm): Atezolizumab +bevacizumab; Arm B (control arm): Sorafenib

• Study Type: Interventional
• Enrollment (Actual): 558
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Bankstown, New South Wales, Australia, 2200
      • Bankstown-Lidcombe Hospital
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital
  • South Australia
    • Woodville, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital
  • Victoria
    • St Albans, Victoria, Australia, 3021
      • Sunshine Hospital
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Ottawa Hospital Research Institute
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H2X 0A9
      • Centre Hospitalier de l'Universite de Montreal (CHUM)
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre - Glen Site
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China, 100050
    • Beijing Friendship Hospital
  • Beijing City, China, 100032
    • Peking Union Medical College Hospital
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Changchun, China, 132013
    • Jilin Cancer Hospital
  • Changsha CITY, China, 410013
    • Hunan Cancer Hospital
  • Foshan, China, 510000
    • The First People's Hospital of Foshan; Local Ethic Committee
  • Fuzhou, China, 110016
    • The 900th Hospital of PLA joint service support force
  • Guangzhou, China, 510515
    • Nanfang Hospital, Southern Medical University
  • Guangzhou City, China, 510663
    • Sun Yet-sen University Cancer Center
  • Hangzhou, China, 310003
    • The First Affiliated Hospital of College of Medicine, Zhejiang University
  • Hangzhou City, China, 310022
    • Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department
  • Hangzhou City, China, 310018
    • Sir Run Run Shaw Hospital
  • Harbin, China, 150081
    • Harbin Medical University Cancer Hospital
  • Hefei, China, 230022
    • The First Affiliated Hospital of Anhui Medical University
  • Hefei City, China, 230031
    • Anhui Province Cancer Hospital
  • Jinan, China, 250031
    • General Hospital of Jinan Military Command of PLA
  • Nanjing City, China, 210002
    • The 81st Hospital of P.L.A.
  • Shanghai, China, 200032
    • Zhongshan Hospital Fudan University
  • Shanghai City, China, 200120
    • Fudan University Shanghai Cancer Center
  • Wuhan, China, 430030
    • Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech
• Czechia
  • Brno, Czechia, 656 53
    • Masarykuv onkologicky ustav
  • Olomouc, Czechia, 779 00
    • Fakultni nemocnice Olomouc; Onkologicka klinika
• France
  • Lille, France, 59037
    • Hopital Claude Huriez;Gastro Enterologie
  • Lyon, France, 69317
    • Hopital De La Croix Rousse; Hepatologie Gastro Enterologie
  • Marseille, France, 13385
    • Hopital Timone Adultes; Gastro Enterologie
  • Montpellier, France, 34295
    • Hopital Saint-Eloi; Hepatologie-Gastro-Enterologie
  • Nantes, France, 44093
    • Hopital Hotel Dieu Et Hme; Hepatologie Gastro Enterologie
  • Nice Cedex, France, 06202
    • CHU Nice - Hôpital de l'Archet 2; service Hepato gastro enterologie
  • Rouen, France, 76031
    • Hopital Charles Nicolle; Gastroenterologie
  • Strasbourg, France, 67098
    • Hopital Hautepierre; Gastro Enterologie
  • Vandoeuvre-les-nancy, France, 54511
    • Hôpital d'Adultes; Service hépato-gastro-entérologie
  • Villejuif, France, 94805
    • Institut Gustave Roussy; Gastro-Enterologie
• Germany
  • Berlin, Germany, 13353
    • Campus Virchow-Klinikum Charité Centrum 13; Medizinische Klinik; Abt.Hepatologie u.Gastroenterologie
  • Frankfurt, Germany, 60590
    • Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik I
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg-Eppendorf; I. Medizinische Klinik - Gastroenterologie
  • Hannover, Germany, 30625
    • Med. Hochschule Hannover; Gastroenterologie
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig Medizinische Klinik II Gastroenterolog. u. Hepatolog.
  • Mainz, Germany, 55131
    • Uniklinik Mainz; I. Medizinische Klinik
  • Regensburg, Germany, 93053
    • Klinikum der Uni Regensburg; Klinik f.Innere Medizin I Abt. Hämatologie und Internistische Onkologie
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital; Dept. Of Haematology & Oncology
  • Shatin, Hong Kong
    • Prince of Wales Hosp; Dept. Of Clinical Onc
• Italy
  • Campania
    • Benevento, Campania, Italy, 82100
      • Az. Osp. Rummo; Oncologia Medica
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
  • Piemonte
    • Orbassano, Piemonte, Italy, 10043
      • Az. Osp. S. Luigi Gonzaga; Divisione Di Oncologia Medica
  • Sardegna
    • Cagliari, Sardegna, Italy, 09100
      • A.O.U. Cagliari-P.O. Monserrato;U.O. Oncologia
  • Toscana
    • Pisa, Toscana, Italy, 56126
      • Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria ? Polo Oncologico
  • Veneto
    • Padova, Veneto, Italy, 35128
      • IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima
• Japan
  • Chiba, Japan, 260-8677
    • Chiba University Hospital
  • Chiba, Japan, 277-8577
    • National Cancer Center Hospital East
  • Fukuoka, Japan, 830-0011
    • Kurume University Hospital
  • Hokkaido, Japan, 060-8648
    • Hokkaido University Hospital
  • Hokkaido, Japan, 060-0033
    • Sapporo Kosei Genaral Hospital
  • Ishikawa, Japan, 920-8641
    • Kanazawa University Hospital
  • Kanagawa, Japan, 252-0375
    • Kitasato University Hospital
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital
  • Osaka, Japan, 589-8511
    • Kindai University Hospital
  • Osaka, Japan, 545-8586
    • Osaka Metropolitan University Hospital
  • Saga, Japan, 840-8571
    • Saga-Ken Medical Centre Koseikan
  • Shizuoka, Japan, 411-8777
    • Shizuoka Cancer Center
  • Tokyo, Japan, 180-8610
    • Japanese Red Cross Musashino Hospital
• Korea, Republic of
  • Jeollanam-do, Korea, Republic of, 58128
    • Chonnam National University Hwasun Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Ulsan, Korea, Republic of, 44033
    • Ulsan University Hosiptal
• Poland
  • Gdansk, Poland, 80-219
    • Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii
  • Myslowice, Poland, 41-400
    • ID Clinic
  • Olsztyn, Poland, 10-228
    • SP ZOZ MSWiA z WARMINSKO-MAZURSKIM CENTRUM ONKOLOGII; CLINICAL ONCOLOGY, CLINICAL IMMUNOLOGY
  • Warszawa, Poland, 02-781
    • Narodowy Instytut Onkologii im. Marii Sk?odowskiej-Curie - Pa?stwowy Instytut Badawczy
  • Wroc?aw, Poland, 53-413
    • Dolno?l?skie Centrum Onkologii; Oddzia? Onkologii Klinicznej i Chemioterapii
• Russian Federation
  • Moskovskaja Oblast
    • Moscow, Moskovskaja Oblast, Russian Federation, 115478
      • FSBI "National Medical Research Center of Oncology N.N. Blokhin?; Clinical Biotechnologies
  • Sankt Petersburg
    • Saint Petersburg, Sankt Petersburg, Russian Federation, 197758
      • GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology)
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital; Oncology
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron; Oncology
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos; Servicio de Oncologia
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz; Servicio de Oncologia
  • Madrid, Spain, 28050
    • Centro Integral Oncologico Clara Campal; Servicio de Oncología
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet; Servicio de Oncologia Medica
• Taiwan
  • Tainan, Taiwan, 710
    • Chi-Mei Medical Centre; Hematology & Oncology
  • Tainan, Taiwan, 00704
    • National Cheng Kung University Hospital; Oncology
  • Taipei, Taiwan, 100
    • National Taiwan Uni Hospital; Dept of Oncology
  • Taipei, Taiwan, 00112
    • Veterans General Hospital; Cancer Center
  • Taoyuan County, Taiwan, 333
    • Chang Gung Memorial Hospital-Linkou; Dept of Oncology
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital; Dept of Oncology
  • Manchester, United Kingdom, M2O 4BX
    • Christie Hospital Nhs Trust; Medical Oncology
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85260
      • St. Josephs Hospital and Medical Center
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • La Jolla, California, United States, 92093
      • Uni of California - San Diego; Cancer Center & Dept of Medicine
    • Novato, California, United States, 94589
      • Kaiser Permanente Northern California
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Sacramento Medical Center
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
    • San Francisco, California, United States, 94118
      • Kaiser Permanente - San Francisco Medical Center
    • Santa Monica, California, United States, 90404
      • University of California Los Angeles
    • Walnut Creek, California, United States, 94596
      • Kaiser Permanente - Walnut Creek
  • Colorado
    • Greeley, Colorado, United States, 85234
      • Banner MD Anderson Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University; Wash Uni. Sch. Of Med
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Comprehensive Cancer Center
  • New York
    • New York, New York, United States, 10016
      • Laura and ISAAC Perlmutter Cancer Center at NYU Langone.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Texas
    • Houston, Texas, United States, 77030
      • M.D Anderson Cancer Center; Uni of Texas At Houston
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Inst.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Uncontrolled or symptomatic hypercalcemia
• Treatment with systemic immunostimulatory agents
• Inadequately controlled arterial hypertension
• Prior history of hypertensive crisis or hypertensive encephalopathy
• Evidence of bleeding diathesis or significant coagulopathy
• History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including sub-occlusive disease related to the underlying disease or requirement for routine parenteral hydration
• Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
• Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses
• Local therapy to liver within 28 days prior to initiation of study treatment or non-recovery from side effects of any such procedure
• Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atezolizumab + Bevacizumab; Participants will receive Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator	Drug: Atezolizumab; Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21 day cycle; Drug: Bevacizumab; Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21 day cycle
Active Comparator: Sorafenib; Participants will receive Sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator	Drug: Sorafenib; Sorafenib will be administered by mouth, 400 mg twice per day, on days 1-21 of each 21-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate by IRF-Assessment (ORR-IRF) Per RECIST v1.1 in the Global Population	ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR	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	ORR was defined as the percentage of participants with CR or PR as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver measuring only the residual vital tumor mass in the liver. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR	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	ORR was defined as the percentage of participants with CR or PR as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR	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	DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. 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 mm.	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	DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. 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 mm.	Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)
Duration of Response by Investigator Assessment (DOR-INV) Per RECIST v1.1 in the Global Population	DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. 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 mm.	Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)
PFS-IRF Per HCC mRECIST in the Global Population	PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. 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)
PFS by Investigator Assessment (PFS-INV) Per RECIST v1.1 in the Global Population	PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator 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)
Time to Progression (TTP) by IRF Assessment (TTP-IRF) Per RECIST v1.1 in the Global Population	Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the 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)
TTP-IRF Per HCC mRECIST in the Global Population	Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. 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)
TTP by Investigator Assessment (TTP-INV) Per RECIST v1.1 in the Global Population	Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator 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 by Baseline AFP in the Global Population	OS was defined as the time from randomization to death from any cause. Subpopulations with baseline AFP <400 ng/mL and AFP>/= 400 ng/mL were analyzed.	From randomization to death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)
PFS-IRF Per RECIST v1.1 by Baseline AFP in the Global Population	PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the 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). Subpopulations with baseline AFP <400 ng/mL and AFP>/= 400 ng/mL were analyzed.	Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)
PFS-INV Per RECIST v1.1 by Baseline AFP in the Global Population	PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator 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). Subpopulations with baseline AFP <400 ng/mL and AFP>/= 400 ng/mL were analyzed.	Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)
Time to Deterioration (TTD) in the Global Population	TTD was defined as the time from randomization to the first deterioration (decrease from baseline of >/= 10 points) in the patient-reported health-related global health status/quality of life (GHS /HRQoL), physical function or role function scales of the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for cancer (EORTC) QLQ-C30, maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks.	Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)
Maximum Serum Concentration (Cmax) of Atezolizumab at Cycle 1 in the Global Population		Post-dose on Day 1 of Cycle 1 (cycle length = 21 days)
Trough Serum Concentration (Cmin) of Atezolizumab in the Global Population		Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length = 21 days)
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab in the Global Population		Baseline and post-baseline on Day 1 (pre-dose) of Cycles 2, 3, 4, 8, 12, 16 (cycle length = 21 days) and treatment discontinuation visit (up to approximately 30 months)
Objective Response Rate by IRF-Assessment (ORR-IRF) Per RECIST v1.1 in the China Population	ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR	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 China Population	ORR was defined as the percentage of participants with CR or PR as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver measuring only the residual vital tumor mass in the liver. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR	Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)
ORR by Investigator-Assessment (ORR-INV) Per RECIST v1.1 in the China Population	ORR was defined as the percentage of participants with CR or PR as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. OR=CR+PR	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 China Population	DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. 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 mm.	Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)
Duration of Response by IRF Assessment (DOR-IRF) Per HCC mRECIST in the China Population	DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. 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 mm.	Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)
Duration of Response by Investigator Assessment (DOR-INV) Per RECIST v1.1 in the China Population	DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. 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 mm.	Randomization up to CCOD of 29Aug2019 (up to approximately 18 months)
PFS-IRF Per HCC mRECIST in the China Population	PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. 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)
PFS by Investigator Assessment (PFS-INV) Per RECIST v1.1 in the China Population	PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator 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)
Time to Progression (TTP) by IRF Assessment (TTP-IRF) Per RECIST v1.1 in the China Population	Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the 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)
TTP-IRF Per HCC mRECIST in the China Population	Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. 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)
TTP by Investigator Assessment (TTP-INV) Per RECIST v1.1 in the China Population	Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator 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)
Time to Deterioration (TTD) in the China Population	TTD was defined as the time from randomization to the first deterioration (decrease from baseline of >/= 10 points) in the patient-reported health-related global health status/quality of life (GHS /HRQoL), physical function or role function scales of the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for cancer (EORTC) QLQ-C30, maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks.	Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months)
Maximum Serum Concentration (Cmax) of Atezolizumab in the China Population		Post-dose on Day 1 of Cycle 1 (cycle length = 21 days)
Trough Serum Concentration (Cmin) of Atezolizumab in the China Population		Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length = 21 days)
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab in the China Population		Baseline and post-baseline on Day 1 (pre-dose) of Cycles 2, 3, 4, 8, 12, 16 (cycle length = 21 days) and treatment discontinuation visit (up to approximately 18 months)
Number of Participants With Adverse Events (AEs) in the Global Population	An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	Up to end of study (up to approximately 56 months)
Number of Participants With Adverse Events (AEs) in the China Population	An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	Up to end of study (up to approximately 56 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Kaseb 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.
• Li 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.
• Cheng 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.
• Salem 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.
• Galle 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.
• Wen 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.
• Finn 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2018
• Primary Completion (Actual): August 31, 2020
• Study Completion (Actual): November 17, 2022

Study Registration Dates

• First Submitted: January 31, 2018
• First Submitted That Met QC Criteria: February 9, 2018
• First Posted (Actual): February 15, 2018

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Immune Checkpoint Inhibitors; Sorafenib; Bevacizumab; Atezolizumab
• Other Study ID Numbers: YO40245; 2017-003691-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No