A Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma

Recruitment Status: COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified August 2023 by Hoffmann-La Roche
Sponsor: Hoffmann-La Roche
Information Provided by (Responsible Party): Hoffmann-La Roche

Clinicaltrials.gov Identifier: NCT03434379
Other Study ID Numbers:: YO40245

First Submitted: January 30, 2018
First Posted: February 14, 2018
Results First Posted: August 15, 2021
Last Update Posted: October 22, 2023
Last Verified: August 2023

ClinicalTrials.gov processed this data on October 2023. Link to the current ClinicalTrials.gov record .

Study Details

Study 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

Condition or Disease	Intervention/Treatment
Carcinoma, Hepatocellular	Drug: AtezolizumabDrug: Sorafenib

Study Design

Study Type	Interventional
Actual Enrollment	558 participants
Design Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	None (Open Label)
Primary Purpose	Treatment
Official Title	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
Study Start Date	March 14, 2018
Actual Primary Completion Date	August 30, 2020
Actual Study Completion Date	November 16, 2022

Groups and Cohorts

Group/Cohort	Intervention/Treatment
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
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

Outcome Measures

Primary Outcome Measures

Overall Survival (OS) in the Global Population
OS was defined as the time from randomization to death from any cause.
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).
Overall Survival (OS) in the China Population
OS was defined as the time from randomization to death from any cause.
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).

Secondary Outcome Measures

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
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
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
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.
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.
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.
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).
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).
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).
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).
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).
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.
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.
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.
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.
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.
Maximum Serum Concentration (Cmax) of Atezolizumab at Cycle 1 in the Global Population
Trough Serum Concentration (Cmin) of Atezolizumab in the Global Population
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab in the Global Population
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
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
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
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.
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.
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.
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).
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).
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).
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).
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).
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.
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.
Maximum Serum Concentration (Cmax) of Atezolizumab in the China Population
Trough Serum Concentration (Cmin) of Atezolizumab in the China Population
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab in the China Population

Eligibility Criteria

Ages Eligible for Study	(Adult, Older Adult)
Sexes Eligible for Study	All
Accepts Healthy Volunteers	No
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)

Contacts and Locations

Sponsors and Collaborators	Hoffmann-La Roche
Locations	St. Josephs Hospital and Medical Center \| Phoenix Arizona, United States, 85260City of Hope \| Duarte California, United States, 91010Uni of California - San Diego; Cancer Center & Dept of Medicine \| La Jolla California, United States, 92093Kaiser Permanente Northern California \| Novato California, United States, 94589University of California Irvine Medical Center \| Orange California, United States, 92868Kaiser Permanente Sacramento Medical Center \| Sacramento California, United States, 95825California Pacific Medical Center \| San Francisco California, United States, 94115Kaiser Permanente - San Francisco Medical Center \| San Francisco California, United States, 94118University of California Los Angeles \| Santa Monica California, United States, 90404Kaiser Permanente - Walnut Creek \| Walnut Creek California, United States, 94596Banner MD Anderson Cancer Center \| Greeley Colorado, United States, 85234Georgetown University \| Washington D.C. District of Columbia, United States, 20007Moffitt Cancer Center \| Tampa Florida, United States, 33612Massachusetts General Hospital \| Boston Massachusetts, United States, 02114Henry Ford Health System \| Detroit Michigan, United States, 48202Washington University; Wash Uni. Sch. Of Med \| St Louis Missouri, United States, 63110University of New Mexico Comprehensive Cancer Center \| Albuquerque New Mexico, United States, 87102Laura and ISAAC Perlmutter Cancer Center at NYU Langone. \| New York New York, United States, 10016Thomas Jefferson University \| Philadelphia Pennsylvania, United States, 19107M.D Anderson Cancer Center; Uni of Texas At Houston \| Houston Texas, United States, 77030Swedish Cancer Inst. \| Seattle Washington, United States, 98104Bankstown-Lidcombe Hospital \| Bankstown New South Wales, Australia, 2200St George Hospital \| Kogarah New South Wales, Australia, 2217The Queen Elizabeth Hospital \| Woodville South Australia, Australia, 5011Sunshine Hospital \| St Albans Victoria, Australia, 3021Ottawa Hospital Research Institute \| Ottawa Ontario, Canada, K1Y 4E9Centre hospitalier de l'Universite de Montreal (CHUM) \| Montreal Quebec, Canada, H2X 0A9Jewish General Hospital \| Montreal Quebec, Canada, H3T 1E2McGill University Health Centre - Glen Site \| Montreal Quebec, Canada, H4A 3J1Peking Union Medical College Hospital \| Beijing , China, 100032Beijing Friendship Hospital \| Beijing , China, 100050Beijing Cancer Hospital \| Beijing , China, 100142the First Hospital of Jilin University \| Changchun , China, 130021Jilin Cancer Hospital \| Changchun , China, 132013Hunan Cancer Hospital \| Changsha , China, 410013The First People's Hospital of Foshan; Local Ethic Committee \| Foshan , China, 510000The 900th Hospital of PLA joint service support force \| Fuzhou , China, 110016Nanfang Hospital, Southern Medical University \| Guangzhou , China, 510515Sun Yet-sen University Cancer Center \| Guangzhou , China, 510663The First Affiliated Hospital of College of Medicine, Zhejiang University \| Hangzhou , China, 310003Sir Run Run Shaw Hospital \| Hangzhou , China, 310018Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department \| Hangzhou , China, 310022Harbin Medical University Cancer Hospital \| Harbin , China, 150081The First Affiliated Hospital of Anhui Medical University \| Hefei , China, 230022Anhui Province Cancer Hospital \| Hefei , China, 230031General Hospital of Jinan Military Command of PLA \| Jinan , China, 250031The 81st Hospital of P.L.A. \| Nanjing , China, 210002Zhongshan Hospital Fudan University \| Shanghai , China, 200032Fudan University Shanghai Cancer Center \| Shanghai , China, 200120Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech \| Wuhan , China, 430030Masarykuv onkologicky ustav \| Brno , Czechia, 656 53Fakultni nemocnice Olomouc; Onkologicka klinika \| Olomouc , Czechia, 779 00Hopital Claude Huriez;Gastro Enterologie \| Lille , France, 59037Hopital De La Croix Rousse; Hepatologie Gastro Enterologie \| Lyon , France, 69317Hopital Timone Adultes; Gastro Enterologie \| Marseille , France, 13385Hopital Saint-Eloi; Hepatologie-Gastro-Enterologie \| Montpellier , France, 34295Hopital Hotel Dieu Et Hme; Hepatologie Gastro Enterologie \| Nantes , France, 44093CHU Nice - Hôpital de l'Archet 2; service Hepato gastro enterologie \| Nice , France, 06202Hopital Charles Nicolle; Gastroenterologie \| Rouen , France, 76031Hopital Hautepierre; Gastro Enterologie \| Strasbourg , France, 67098Hôpital d'Adultes; Service hépato-gastro-entérologie \| Vandœuvre-lès-Nancy , France, 54511Institut Gustave Roussy; Gastro-Enterologie \| Villejuif , France, 94805Campus Virchow-Klinikum Charité Centrum 13; Medizinische Klinik; Abt.Hepatologie u.Gastroenterologie \| Berlin , Germany, 13353Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik I \| Frankfurt , Germany, 60590Universitaetsklinikum Hamburg-Eppendorf; I. Medizinische Klinik - Gastroenterologie \| Hamburg , Germany, 20246Med. Hochschule Hannover; Gastroenterologie \| Hanover , Germany, 30625Universitätsklinikum Leipzig Medizinische Klinik II Gastroenterolog. u. Hepatolog. \| Leipzig , Germany, 04103Uniklinik Mainz; I. Medizinische Klinik \| Mainz , Germany, 55131Klinikum der Uni Regensburg; Klinik f.Innere Medizin I Abt. Hämatologie und Internistische Onkologie \| Regensburg , Germany, 93053Queen 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, Italy, 82100IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica \| Meldola Emilia-Romagna, Italy, 47014Az. Osp. S. Luigi Gonzaga; Divisione Di Oncologia Medica \| Orbassano Piedmont, Italy, 10043A.O.U. Cagliari-P.O. Monserrato;U.O. Oncologia \| Cagliari Sardinia, Italy, 09100Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria ? Polo Oncologico \| Pisa Tuscany, Italy, 56126IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima \| Padova Veneto, Italy, 35128Chiba University Hospital \| Chiba , Japan, 260-8677National Cancer Center Hospital East \| Chiba , Japan, 277-8577Kurume University Hospital \| Fukuoka , Japan, 830-0011Sapporo Kosei Genaral Hospital \| Hokkaido , Japan, 060-0033Hokkaido University Hospital \| Hokkaido , Japan, 060-8648Kanazawa University Hospital \| Ishikawa , Japan, 920-8641Kitasato University Hospital \| Kanagawa , Japan, 252-0375Kumamoto University Hospital \| Kumamoto , Japan, 860-8556Osaka Metropolitan University Hospital \| Osaka , Japan, 545-8586Kindai University Hospital \| Osaka , Japan, 589-8511Saga-ken Medical Centre Koseikan \| Saga , Japan, 840-8571Shizuoka Cancer Center \| Shizuoka , Japan, 411-8777Japanese Red Cross Musashino Hospital \| Tokyo , Japan, 180-8610Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii \| Gdansk , Poland, 80-219ID Clinic \| Mysłowice , Poland, 41-400SP ZOZ MSWiA z WARMINSKO-MAZURSKIM CENTRUM ONKOLOGII; CLINICAL ONCOLOGY, CLINICAL IMMUNOLOGY \| Olsztyn , Poland, 10-228Narodowy Instytut Onkologii im. Marii Sk?odowskiej-Curie - Pa?stwowy Instytut Badawczy \| Warsaw , Poland, 02-781Dolno?l?skie Centrum Onkologii; Oddzia? Onkologii Klinicznej i Chemioterapii \| Wroc?aw , Poland, 53-413FSBI "National Medical Research Center of Oncology N.N. Blokhin?; Clinical Biotechnologies \| Moscow Moscow Oblast, Russia, 115478GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology) \| Saint Petersburg Sankt-Peterburg, Russia, 197758National Cancer Centre \| Singapore , Singapore, 169610Tan Tock Seng Hospital; Oncology \| Singapore , Singapore, 308433Chonnam National University Hwasun Hospital \| Jeollanam-do , South Korea, 58128Seoul National University Hospital \| Seoul , South Korea, 03080Severance Hospital, Yonsei University Health System \| Seoul , South Korea, 03722Asan Medical Center \| Seoul , South Korea, 05505Samsung Medical Center \| Seoul , South Korea, 06351Ulsan University Hosiptal \| Ulsan , South Korea, 44033Hospital Universitari Vall d'Hebron; Oncology \| Barcelona , Spain, 08035Hospital Clinico San Carlos; Servicio de Oncologia \| Madrid , Spain, 28040Hospital Universitario La Paz; Servicio de Oncologia \| Madrid , Spain, 28046Centro Integral Oncologico Clara Campal; Servicio de Oncología \| Madrid , Spain, 28050Hospital Universitario Miguel Servet; Servicio de Oncologia Medica \| Zaragoza , Spain, 50009National Cheng Kung University Hospital; Oncology \| Tainan , Taiwan, 00704Chi-Mei Medical Centre; Hematology & Oncology \| Tainan , Taiwan, 710Veterans General Hospital; Cancer Center \| Taipei , Taiwan, 00112National Taiwan Uni Hospital; Dept of Oncology \| Taipei , Taiwan, 100Chang Gung Memorial Hospital-Linkou; Dept of Oncology \| Taoyuan County , Taiwan, 333Beatson West of Scotland Cancer Centre \| Glasgow , United Kingdom, G12 0YNRoyal Free Hospital; Dept of Oncology \| London , United Kingdom, NW3 2QGKing'S College Hospital \| London , United Kingdom, SE5 9RSChristie Hospital Nhs Trust; Medical Oncology \| Manchester , United Kingdom, M2O 4BX
Investigators	Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full Text)

Documents provided by Hoffmann-La Roche: Study Protocol January 31, 2021Documents provided by Hoffmann-La Roche: Statistical Analysis Plan February 21, 2019

More Information

Publications

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. 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.

Additional Relevant MeSH Terms

Carcinoma, HepatocellularAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases