A Study of Atezolizumab Plus Bevacizumab Versus Active Surveillance as Adjuvant Therapy in Patients With Hepatocellular Carcinoma at High Risk of Recurrence After Surgical Resection or Ablation (IMbrave050)

A Phase III, Multicenter, Randomized, Open-Label Study of Atezolizumab (Anti-PD-L1 Antibody) Plus Bevacizumab Versus Active Surveillance as Adjuvant Therapy in Patients With Hepatocellular Carcinoma at High Risk of Recurrence After Surgical Resection or Ablation

This study will evaluate the efficacy and safety of adjuvant therapy with atezolizumab plus bevacizumab compared with active surveillance in participants with completely resected or ablated hepatocellular carcinoma (HCC) who are at high risk for disease recurrence.

Study Overview

• Status: Active, not recruiting
• Conditions: Carcinoma, Hepatocellular
• Intervention / Treatment: Drug: Bevacizumab; Drug: Atezolizumab

• Study Type: Interventional
• Enrollment (Actual): 668
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital Sydney
• Austria
  • Graz, Austria, 8036
    • LKH-Univ. Klinikum Graz
  • Klagenfurt, Austria, 9020
    • Klinikum Klagenfurt am Wörtersee
  • Vienna, Austria, 1090
    • Medizinische Universitat Wien
• Belgium
  • Bonheiden, Belgium, 2820
    • Imeldaziekenhuis
  • Roeselare, Belgium, 8800
    • AZ Delta (Campus Rumbeke)
• Brazil
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 41253-190
      • Hospital Sao Rafael - HSR
  • Federal District
    • Brasília, Federal District, Brazil, 70200-730
      • Sociedade Beneficente de Senhoras Hospital Sirio Libanes
  • Paraná
    • Cascavel, Paraná, Brazil, 85806-300
      • Hospital do Cancer UOPECCAN
  • São Paulo
    • São Paulo, São Paulo, Brazil, 01323-020
      • Hospital Alemao Oswaldo Cruz
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Gordon & Leslie Diamond Health Care Centre
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre - Glen Site
• China
  • Anhui, China, 230001
    • Anhui Provincial Hospital
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China, 100730
    • Peking Union Medical College Hospital
  • Bengbu, China, 233004
    • Affiliated Hospital of Bengbu Medical College
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Chengdu, China, 610041
    • West China Hospital, Sichuan University
  • Chongqing, China, 400042
    • Daping Hospital of Third Military Medical University
  • Dalian, China, 116027
    • The Second Affiliated Hospital of Dalian Medical University
  • Fuzhou, China, 350014
    • Fujian Cancer Hospital
  • Fuzhou, China, 350025
    • Mengchao Hepatobiliary Hospital of Fujian Medical University
  • Guangzhou, China, 510060
    • Sun Yet-sen University Cancer Center
  • Guangzhou, China, 510515
    • Nanfang Hospital, Southern Medical University
  • Guangzhou, China, 510000
    • Cancer Center of Guangzhou Medical University
  • Guangzhou, China, 510280
    • Zhujiang Hospital, Southern Medical University
  • Hangzhou, China, 310022
    • Zhejiang Cancer Hospital
  • Harbin, China, 150081
    • Harbin Medical University Cancer Hospital
  • Hefei, China, 230601
    • The Second Affiliated Hospital of Anhui Medical University
  • Hefei, China, 12345
    • Anhui Province Cancer Hospital
  • Jinan, China, 250117
    • Shandong Cancer Hospital
  • Nanjing, China, 210009
    • Zhongda Hospital Affiliated to Southeast University
  • Nanjing, China, 210029
    • Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
  • Nanjing, China, 210002
    • The 81st Hospital of P.L.A.
  • Nanning, China, 530021
    • The First Affiliate Hospital of Guangxi Medical University
  • Nanning, China, 530021
    • Guangxi Cancer Hospital of Guangxi Medical University
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center
  • Shanghai, China, 200040
    • Huashan Hospital affiliated to Fudan University
  • Shanghai, China, 200127
    • Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
  • Shanghai, China
    • Zhongshan Hospital Fudan Unvierstiy
  • Shenyang, China, 110004
    • Shengjing Hospital of China Medical University
  • Shenyang, China, 110001
    • The First Affiliated Hospital of China Medical University
  • Tianjin, China, 300060
    • Tianjin cancer hospital
  • Wuhan, China, 430060
    • Renmin Hospital of Wuhan University
  • Wuhan, China, 430071
    • Zhongnan Hospital of Wuhan University
  • Wuhan, China, 430022
    • Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology
  • Yangzhou, China
    • Northern Jangsu People's Hospital
  • Ürümqi, China, 830000
    • The Tumor Hospital of Xinjiang Medical University
• Costa Rica
  • San José, Costa Rica, 10103
    • Clinica CIMCA
• Czechia
  • Brno, Czechia, 625 00
    • Fakultni Nemocnice Brno
  • Prague, Czechia, 140 59
    • Fakultni Thomayerova nemocnice
• France
  • Besançon, France, 25030
    • Hopital Jean Minoz
  • Bobigny, France, 93009
    • Hôpital Avicenne - Groupement Hospitalier Universitaire Paris Seine St Denis
  • La Tronche, France, 38700
    • Hôpital Albert Michallon
  • Marseille, France, 13285
    • Fondation Hôpital Saint Joseph
  • Pessac, France, 33604
    • CHU Bordeaux - Hôpital Haut-Lévêque
  • Reims, France, 51092
    • Hopital Robert Debre
  • Rennes, France, 35033
    • Hôpital de Pontchaillou
  • Toulouse, France, 31059
    • CHU de Toulouse - Hôpital Rangueil
  • Vandœuvre-lès-Nancy, France, 54511
    • Hopitaux de Brabois - Gastro-Entereologie
• Germany
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I.
  • Frankfurt am Main, Germany, 60590
    • Klinik Johann Wolfgang von Goethe Uni
  • Regensburg, Germany, 93053
    • Klinikum der Uni Regensburg
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Shatin, Hong Kong
    • Prince of Wales Hospital
• Italy
  • Emilia-Romagna
    • Parma, Emilia-Romagna, Italy, 43100
      • Ospedale Regionale Di Parma
  • Lombardy
    • Milan, Lombardy, Italy, 20122
      • Ospedale Maggiore Policlinico
    • Milan, Lombardy, Italy, 20142
      • Asst Santi Paolo E Carlo
  • Tuscany
    • Pisa, Tuscany, Italy, 56100
      • Azlenda Ospendaliero-Universitaria Pisana
• Japan
  • Chiba, Japan, 260-8677
    • Chiba University Hospital
  • Ehime, Japan, 790-0024
    • Ehime Prefectural Central Hospital
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital
  • Hokkaido, Japan, 060-0033
    • Sapporo Kosei General Hospital
  • Hyōgo, Japan, 670-8540
    • Japanese Red Cross Society Himeji Hospital
  • Hyōgo, Japan, 663-8501
    • Hyogo Medical University Hospital
  • Ishikawa, Japan, 920-8641
    • Kanazawa University Hospital
  • Kanagawa, Japan, 241-8515
    • Kanagawa Cancer Center
  • Kanagawa, Japan, 252-0375
    • Kitasato University Hospital
  • Kanagawa, Japan, 232-0024
    • Yokohama City University Medical Center
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital
  • Osaka, Japan, 543-8555
    • Osaka Red Cross Hospital
  • Osaka, Japan, 589-8511
    • Kindai University Hospital
  • Tokushima, Japan, 770-8503
    • Tokushima University Hospital
  • Tokyo, Japan, 180-8610
    • Japanese Red Cross Musashino Hospital
  • Tokyo, Japan, 105-8470
    • Toranomon Hospital
  • Tokyo, Japan, 113-8655
    • The University of Tokyo Hospital
• Mexico
  • Oaxaca City, Mexico, 68000
    • Oaxaca Site Management Organization
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Filios Alta Medicina
• Netherlands
  • Maastricht, Netherlands, 6229 HX
    • Maastricht University Medical Center
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
• Peru
  • Lima, Peru, 15038
    • Instituto Nacional de Enfermedades Neoplasicas
  • Lima, Peru, 15088
    • Clínica San Gabriel
• Poland
  • Warsaw, Poland, 02-034
    • Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie
• Russia
  • Moscow Oblast
    • Moscow, Moscow Oblast, Russia, 119991
      • First Moscow State Medical University n.a. I.M. Sechenov
    • Moskva, Moscow Oblast, Russia, 105229
      • Group of companies "Medci"
  • Niznij Novgorod
    • Nizhny Novgorod, Niznij Novgorod, Russia, 603109
      • Clinical hospital #1, FBHI Volga district medical center, Federal Medical and Biological Agency
  • Sankt-Peterburg
    • Pesochny, Sankt-Peterburg, Russia, 197758
      • Russian Scientific Center of Radiology and Surgical Technologies
• Singapore
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital
  • Singapore, Singapore, 168583
    • National Cancer Centre
• South Korea
  • Busan, South Korea, 49241
    • Pusan National University Hospital
  • Daegu, South Korea, 41944
    • Kyungpook National University Hospital
  • Gyeonggi-do, South Korea, 13496
    • CHA Bundang Medical Center
  • Gyeonggi-do, South Korea, 13620
    • Seoul National University Bundang Hospital
  • Gyeonggi-do, South Korea, 16499
    • Ajou University Medical Center
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 06273
    • Gangnam Severance Hospital
  • Seoul, South Korea, 06591
    • Seoul St Mary's Hospital
  • Seoul, South Korea, 07061
    • Boramae Medical Center
  • Seoul, South Korea, 6351
    • Samsung Medical Center
  • Ulsan, South Korea, 44033
    • Ulsan University Hosiptal
• Spain
  • Badajoz, Spain, 06080
    • Hospital Universitario Infanta Cristina
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro
• Taiwan
  • Chang-hua, Taiwan, 500
    • Changhua Christian Hospital
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 100
    • National Taiwan Uni Hospital
  • Taoyuan District, Taiwan, 333
    • Chang Gung Medical Foundation - Linkou
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
  • Bangkok, Thailand, 10400
    • Rajavithi Hospital
  • Chiang Rai, Thailand, 57000
    • Chiang Rai Prachanukroh Hospital
  • Lak Si, Thailand, 10210
    • Chulabhorn Hospital
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01120
    • Adana Baskent University Hospital
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Texas
    • Dallas, Texas, United States, 75390
      • The University of Texas Southwestern Medical Center at Dallas
    • Houston, Texas, United States, 77030
      • Md Anderson Cancer Center
  • 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:

• Participants with a first diagnosis of HCC who have undergone either a curative resection or ablation (radiofrequency ablation [RFA] or microwave ablation [MVA] only) within 4-12 weeks prior to randomization
• Documented diagnosis of HCC that has been completely resected or ablated (RFA or MVA only)
• Absence of major macrovascular invasion (except Vp1/Vp2) and extrahepatic spread
• Absence of extrahepatic spread as confirmed by CT or MRI scan of the chest, abdomen, pelvis, and head prior to and following curative procedure
• Full recovery from surgical resection or ablation within 4 weeks prior to randomization
• High risk for HCC recurrence after resection or ablation
• For patients who received post-operative transarterial chemoembolization: full recovery from the procedure within 4 weeks prior to randomization
• For patients with resected HCC, availability of a representative baseline tumor tissue sample
• ECOG Performance Status of 0 or 1
• Child-Pugh Class A status
• Adequate hematologic and end-organ function
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm

Exclusion Criteria:

• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• Evidence of residual, recurrent, or metastatic disease at randomization
• Clinically significant ascites
• History of hepatic encephalopathy
• Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to randomization
• Have received more than 1 cycle of adjuvant TACE following surgical resection
• 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 CT scan
• Significant cardiovascular disease within 3 months prior to Day 1 of Cycle 1, unstable arrhythmia, or unstable angina
• 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
• Active tuberculosis
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of atezolizumab or within 6 months after the final dose of bevacizumab. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to Day 1 of Cycle 1.
• Co-infection with HBV and HCV
• Co-infection with HBV and hepatitis D viral infection
• Clinical significant uncontrolled or symptomatic hypercalcemia
• Any treatment for HCC prior to resection or ablation, including systemic therapy and locoregional therapy such as TACE
• Treatment with systemic immunostimulatory or immunosuppressive agents
• Inadequately controlled arterial hypertension
• History of hypertensive crisis or hypertensive encephalopathy
• Significant vascular disease
• Evidence of bleeding diathesis or significant coagulopathy
• Current or recent use of aspirin or full-dose oral or parenteral anticoagulants
• Core biopsy within 3 days of Day 1 of Cycle 1
• History of GI fistula, GI perforation, or intra-abdominal abscess
• Serious non-healing or dehiscing wound
• Major surgical procedure within four weeks
• Chronic daily treatment with a non-steroidal anti-inflammatory drug

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: Arm A (atezolizumab plus bevacizumab); Participants will receive Atezolizumab + Bevacizumab until disease recurrence or unacceptable toxicity.	Drug: Bevacizumab; Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle.; Other Names: Avastin; Drug: Atezolizumab; Atezolizumab 1200 mg will be administered by IV infusion on Day 1 of each 21-day cycle.; Other Names: Tecentriq
No Intervention: Arm B (active surveillance); Active surveillance of participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-Free Survival (RFS), as Determined by IRF	RFS is defined as the time from randomization to the first documented occurrence of intrahepatic or extrahepatic HCC as determined by an IRF, or death from any cause (whichever occurs first).	Baseline up to approximately 33 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RFS Rate at 24 and 36 Months, as Assessed by the Investigator		Randomization up to 24 months and up to 36 months
Overall Survival (OS)	OS is defined as the time from randomization to death from any cause.	Baseline up to approximately 91 months
RFS as Determined by the Investigator	RFS is defined as the time from randomization to the first documented occurrence of intrahepatic or extrahepatic HCC as determined by an investigator, or death from any cause (whichever occurs first).	Baseline up to approximately 91 months
Time to Recurrence (TTR)	TTR defined as the time from randomization to first documented occurrence of intrahepatic or extrahepatic HCC, as determined by the investigator and by an IRF.	Baseline up to approximately 91 months
RFS Rate at 24 and 36 Months, as Assessed by the IRF		Randomization up to 24 months and up to 36 months
OS Rate at 24 and 36 Months	OS rate defined as the proportion of patients who have not experienced death from any cause at 24 and 36 months after randomization.	Baseline to 24 and 36 months
Time to Extrahepatic Spread (EHS) or Macrovascular Invasion	Time to EHS or macrovascular invasion after randomization, defined as the time from randomization to the first appearance of EHS or macrovascular invasion, as determined by the investigator.	Baseline up to approximately 91 months
RFS in Pd-L1-High Subgroup	RFS after randomization as determined by the investigator and by an IRF, among patients in the PD-L1-high subgroup.	Baseline up to approximately 91 months
Percentage of Participants With Adverse Events		Baseline up to approximately 91 months
Serum Concentration of Atezolizumab	Serum concentration of atezolizumab.	Prior to any drug administration on Day 1 of Cycles 1, 2, 3, 4, 8, 12, and 16, and 30 minutes after end of atezolizumab infusion on Day 1 of Cycle 1 (each cycle is 21 days)
Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab	Number of participants with anti-drug antibodies to atezolizumab.	Prior to any drug administration up to approximately 33 month

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Hack SP, Spahn J, Chen M, Cheng AL, Kaseb A, Kudo M, Lee HC, Yopp A, Chow P, Qin S. IMbrave 050: a Phase III trial of atezolizumab plus bevacizumab in high-risk hepatocellular carcinoma after curative resection or ablation. Future Oncol. 2020 May;16(15):975-989. doi: 10.2217/fon-2020-0162. Epub 2020 Apr 30.
• Qin S, Chen M, Cheng AL, Kaseb AO, Kudo M, Lee HC, Yopp AC, Zhou J, Wang L, Wen X, Heo J, Tak WY, Nakamura S, Numata K, Uguen T, Hsiehchen D, Cha E, Hack SP, Lian Q, Ma N, Spahn JH, Wang Y, Wu C, Chow PKH; IMbrave050 investigators. Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 Nov 18;402(10415):1835-1847. doi: 10.1016/S0140-6736(23)01796-8. Epub 2023 Oct 20.

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2019
• Primary Completion (Actual): October 21, 2022
• Study Completion (Estimated): May 15, 2026

Study Registration Dates

• First Submitted: September 23, 2019
• First Submitted That Met QC Criteria: September 23, 2019
• First Posted (Actual): September 25, 2019

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab; atezolizumab
• Other Study ID Numbers: WO41535; 2019-002491-14 (EudraCT Number); 2023-504303-86-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No