Carcinoma, HepatocellularPhase 3IMbrave050NCT04102098
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
A Phase 3 study testing Atezolizumab and Bevacizumab in people with Carcinoma, Hepatocellular, run by Hoffmann-La Roche at 134 sites in 26 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- Atezolizumab and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 668 participants
- Where
- 134 sitesin 26 countries
- Study dates
- 31 Dec 2019to 15 May 2026
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
134 sites in 26 countries.
134 sites in 26 countries
China36 sites
Anhui Provincial Hospital
Anhui, 230001
Beijing Cancer Hospital
Beijing, 100142
Peking Union Medical College Hospital
Beijing, 100730
Affiliated Hospital of Bengbu Medical College
Bengbu, 233004
The First Hospital of Jilin University
Changchun, 130021
West China Hospital, Sichuan University
Chengdu, 610041
Daping Hospital of Third Military Medical University
Chongqing, 400042
The Second Affiliated Hospital of Dalian Medical University
Dalian, 116027
Fujian Cancer Hospital
Fuzhou, 350014
Mengchao Hepatobiliary Hospital Of Fujian Medical University
Fuzhou, 350025
Cancer Center of Guangzhou Medical University
Guangzhou, 510000
Sun Yet-sen University Cancer Center
Guangzhou, 510060
Zhujiang Hospital, Southern Medical University
Guangzhou, 510280
Nanfang Hospital, Southern Medical University
Guangzhou, 510515
Zhejiang Cancer Hospital
Hangzhou, 310022
Harbin Medical University Cancer Hospital
Harbin, 150081
Anhui Province Cancer Hospital
Hefei, 12345
The Second Affiliated Hospital of Anhui Medical University
Hefei, 230601
Shandong Cancer Hospital
Jinan, 250117
The 81st Hospital of P.L.A.
Nanjing, 210002
Zhongda Hospital Affiliated to Southeast University
Nanjing, 210009
Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
Nanjing, 210029
Guangxi Cancer Hospital of Guangxi Medical University
Nanning, 530021
The First Affiliate Hospital of Guangxi Medical University
Nanning, 530021
Fudan University Shanghai Cancer Center
Shanghai, 200032
Huashan Hospital Affiliated to Fudan University
Shanghai, 200040
Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, 200127
Zhongshan Hospital Fudan Unvierstiy
Shanghai
The First Affiliated Hospital of China Medical University
Shenyang, 110001
Shengjing Hospital of China Medical University
Shenyang, 110004
Tianjin Cancer Hospital
Tianjin, 300060
The Tumor Hospital of Xinjiang Medical University
Ürümqi, 830000
Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology
Wuhan, 430022
Renmin Hospital of Wuhan University
Wuhan, 430060
Zhongnan Hospital of Wuhan University
Wuhan, 430071
Northern Jangsu People's Hospital
Yangzhou
Japan17 sites
Chiba University Hospital
Chiba, 260-8677
Ehime Prefectural Central Hospital
Ehime, 790-0024
Hiroshima University Hospital
Hiroshima, 734-8551
Sapporo Kosei General Hospital
Hokkaido, 060-0033
Hyogo Medical University Hospital
Hyōgo, 663-8501
Japanese Red Cross Society Himeji Hospital
Hyōgo, 670-8540
Kanazawa University Hospital
Ishikawa, 920-8641
Yokohama City University Medical Center
Kanagawa, 232-0024
Kanagawa Cancer Center
Kanagawa, 241-8515
Kitasato University Hospital
Kanagawa, 252-0375
Kumamoto University Hospital
Kumamoto, 860-8556
Osaka Red Cross Hospital
Osaka, 543-8555
Kindai University Hospital
Osaka, 589-8511
Tokushima University Hospital
Tokushima, 770-8503
Toranomon Hospital
Tokyo, 105-8470
The University of Tokyo Hospital
Tokyo, 113-8655
Japanese Red Cross Musashino Hospital
Tokyo, 180-8610
South Korea13 sites
Pusan National University Hospital
Busan, 49241
Kyungpook National University Hospital
Daegu, 41944
CHA Bundang Medical Center
Gyeonggi-do, 13496
Seoul National University Bundang Hospital
Gyeonggi-do, 13620
Ajou University Medical Center
Gyeonggi-do, 16499
Seoul National University Hospital
Seoul, 03080
Severance Hospital, Yonsei University Health System
Seoul, 03722
Asan Medical Center
Seoul, 05505
Gangnam Severance Hospital
Seoul, 06273
Seoul St Mary's Hospital
Seoul, 06591
Boramae Medical Center
Seoul, 07061
Samsung Medical Center
Seoul, 6351
Ulsan University Hosiptal
Ulsan, 44033
France9 sites
Hopital Jean Minoz
Besançon, 25030
Hôpital Avicenne - Groupement Hospitalier Universitaire Paris Seine St Denis
Bobigny, 93009
Hôpital Albert Michallon
La Tronche, 38700
Fondation Hopital Saint Joseph
Marseille, 13285
CHU Bordeaux - Hôpital Haut-Lévêque
Pessac, 33604
Hopital Robert Debre
Reims, 51092
Hopital de Pontchaillou
Rennes, 35033
CHU de Toulouse - Hôpital Rangueil
Toulouse, 31059
Hopitaux de Brabois - Gastro-Entereologie
Vandœuvre-lès-Nancy, 54511
United States8 sites
Mercy Medical Center
Baltimore, Maryland, 21202
The University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390
Henry Ford Health System
Detroit, Michigan, 48202
MD Anderson Cancer Center
Houston, Texas, 77030
Kaiser Permanente Los Angeles
Los Angeles, California, 90027
Columbia University Medical Center
New York, New York, 10032
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Swedish Cancer Inst.
Seattle, Washington, 98104
Taiwan5 sites
Changhua Christian Hospital
Chang-hua, 500
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 807
National Taiwan Uni Hospital
Taipei, 100
Taipei Veterans General Hospital
Taipei, 112
Chang Gung Medical Foundation - Linkou
Taoyuan, 333
Brazil4 sites
Sociedade beneficente de senhoras Hospital Sirio Libanes
Brasília, Federal District, 70200-730
Hospital do Cancer UOPECCAN
Cascavel, Paraná, 85806-300
Hospital Sao Rafael - HSR
Salvador, Estado de Bahia, 41253-190
Hospital Alemao Oswaldo Cruz
São Paulo, São Paulo, 01323-020
Germany4 sites
Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I.
Bonn, 53127
Klinik Johann Wolfgang von Goethe Uni
Frankfurt am Main, 60590
Klinikum der Uni Regensburg
Regensburg, 93053
Universitätsklinikum Ulm
Ulm, 89081
Italy4 sites
Ospedale Maggiore Policlinico
Milan, Lombardy, 20122
Asst Santi Paolo E Carlo
Milan, Lombardy, 20142
Ospedale Regionale Di Parma
Parma, Emilia-Romagna, 43100
Azlenda Ospendaliero-Universitaria Pisana
Pisa, Tuscany, 56100
Russia4 sites
First Moscow State Medical University n.a. I.M. Sechenov
Moscow, Moscow Oblast, 119991
Group of companies "Medci"
Moskva, Moscow Oblast, 105229
Clinical hospital #1, FBHI Volga district medical center, Federal Medical and Biological Agency
Nizhny Novgorod, Niznij Novgorod, 603109
Russian Scientific Center of Radiology and Surgical Technologies
Pesochny, Sankt-Peterburg, 197758
Thailand4 sites
Rajavithi Hospital
Bangkok, 10400
Siriraj Hospital
Bangkok, 10700
Chiang Rai Prachanukroh Hospital
Chiang Rai, 57000
Chulabhorn Hospital
Lak Si, 10210
Austria3 sites
Lkh-Univ. Klinikum Graz
Graz, 8036
Klinikum Klagenfurt am Wörtersee
Klagenfurt, 9020
Medizinische Universität Wien
Vienna, 1090
Spain3 sites
Hospital Universitario Infanta Cristina
Badajoz, 06080
Hospital General Universitario Gregorio Marañon
Madrid, 28007
Hospital Universitario Puerta de Hierro
Majadahonda, Madrid, 28222
Belgium2 sites
Imeldaziekenhuis
Bonheiden, 2820
AZ Delta (Campus Rumbeke)
Roeselare, 8800
Canada2 sites
McGill University Health Centre - Glen Site
Montreal, Quebec, H4A 3J1
Gordon & Leslie Diamond Health Care Centre
Vancouver, British Columbia, V5Z 1M9
Czechia2 sites
Fakultni nemocnice Brno
Brno, 625 00
Fakultni Thomayerova Nemocnice
Prague, 140 59
Hong Kong2 sites
Queen Mary Hospital
Hong Kong
Prince of Wales Hospital
Shatin
Mexico2 sites
Filios Alta Medicina
Monterrey, Nuevo León, 64460
Oaxaca Site Management Organization
Oaxaca City, 68000
Peru2 sites
Instituto Nacional de Enfermedades Neoplasicas
Lima, 15038
Clínica San Gabriel
Lima, 15088
Singapore2 sites
National Cancer Centre
Singapore, 168583
Tan Tock Seng Hospital
Singapore, 308433
Australia1 site
St Vincent's Hospital Sydney
Darlinghurst, New South Wales, 2010
Netherlands1 site
Maastricht University Medical Center
Maastricht, 6229 HX
Poland1 site
Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie
Warsaw, 02-034
Turkey (Türkiye)1 site
Adana Baskent University Hospital
Adana, 01120
About this study
Official title: 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.
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- Atezolizumab, Bevacizumab
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtezolizumabDrug
Also called Tecentriq
Atezolizumab 1200 mg will be administered by IV infusion on Day 1 of each 21-day cycle.
BevacizumabDrug
Also called Avastin
Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Arm A (atezolizumab plus bevacizumab) | Experimental | Participants will receive Atezolizumab + Bevacizumab until disease recurrence or unacceptable toxicity. Receives: Drug: Atezolizumab; Drug: Bevacizumab |
| Arm B (active surveillance) | No intervention | Active surveillance of participants. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline up to approximately 33 months
Secondary outcomes (11)
Overall Survival (OS)
OS is defined as the time from randomization to death from any cause.
Measured: 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).
Measured: 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.
Measured: Baseline up to approximately 91 months
RFS Rate at 24 and 36 Months, as Assessed by the IRF
Measured: Randomization up to 24 months and up to 36 months
RFS Rate at 24 and 36 Months, as Assessed by the Investigator
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline up to approximately 91 months
Percentage of Participants With Adverse Events
Measured: Baseline up to approximately 91 months
Serum Concentration of Atezolizumab
Serum concentration of atezolizumab.
Measured: 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.
Measured: Prior to any drug administration up to approximately 33 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2019
- Study start31 Dec 2019
- Primary completion21 Oct 2022
- Study completion15 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 668 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04102098
- Sponsor's protocol ID
- WO41535
- Other IDs
- 2019-002491-14, 2023-504303-86-00, 2023, 2019
- Acronym
- IMbrave050
- Status last verified
- May 2026
- First submitted
- 23 Sep 2019
- Last updated
- 18 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
Yopp A, Chen M, Cheng AL, Kaseb A, Kudo M, Lee HC, Cha E, Hack SP, Lian Q, Spahn J, Wu C, Qin S, Chow PK. Updated data from IMbrave050: Adjuvant atezolizumab plus bevacizumab for high-risk hepatocellular carcinoma. J Hepatol. 2026 Jun;84(6):1102-1111. doi: 10.1016/j.jhep.2026.01.006. Epub 2026 Jan 22.
PubMed 41580093Qin 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.
PubMed 37871608Hack 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.
PubMed 32352320