A Study of Atezolizumab With Lenvatinib or Sorafenib Versus Lenvatinib or Sorafenib Alone in Hepatocellular Carcinoma Previously Treated With Atezolizumab and Bevacizumab (IMbrave251)

May 13, 2026 updated by: Hoffmann-La Roche

A Phase III, Open-Label, Randomized Study of Atezolizumab With Lenvatinib or Sorafenib Versus Lenvatinib or Sorafenib Alone in Hepatocellular Carcinoma Previously Treated With Atezolizumab and Bevacizumab

This is a Phase III, open-label, multicenter, randomized, two-arm study designed to evaluate the efficacy and safety of atezolizumab plus either lenvatinib or sorafenib versus lenvatinib or sorafenib alone in participants with locally advanced or metastatic Hepatocellular Carcinoma (HCC) who have progressed on prior systemic treatment with atezolizumab plus bevacizumab combination.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

557

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Innsbruck, Austria, 6020
        • Medizinische Universität Innsbruck
      • Salzburg, Austria, 5020
        • Uniklinikum Salzburg, LKH
      • Sankt Pölten, Austria, 3100
        • Universitätsklinikum St. Pölten
      • Vienna, Austria, 1100
        • Klinik Favoriten
  • Belgium
      • Brasschaat, Belgium, 2930
        • AZ Klina
      • Brussels, Belgium, 1200
        • Cliniques Universitaires St-Luc
      • Leuven, Belgium, 3000
        • UZ Leuven
      • Roeselare, Belgium, 8800
        • AZ Delta (Campus Rumbeke)
  • Brazil
      • Rio de Janeiro, Brazil, 22290-160
        • Clinicas Oncologicas Integradas - COI
      • São Paulo, Brazil, 01321-00
        • Beneficencia Portuguesa de Sao Paulo
    • Minas Gerais
      • Belo Horizonte, Minas Gerais, Brazil, 30110-160
        • Hospital Felicio Rocho
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
        • Hospital Sao Lucas - PUCRS
      • Porto Alegre, Rio Grande do Sul, Brazil, 90035-000
        • Hospital Moinhos de Vento
    • Santa Catarina
      • Florianópolis, Santa Catarina, Brazil, 88020-210
        • Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN
  • Bulgaria
      • Panagyurishte, Bulgaria, 4500
        • Multiprofile Hospital for Active Treatment Uni Hospital
      • Plovdiv, Bulgaria, 4004
        • Complex Oncological Center - Plovdiv, EOOD
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Arthur J.E. Child Comprehensive Cancer Center-Calgary
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Juravinski Cancer Centre
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Center
  • China
      • Changsha, China, 410013
        • Hunan Cancer Hospital
      • Fuzhou, China, 350001
        • Fujian Provincial Hospital
      • Guangzhou, China, 510515
        • Nanfang Hospital, Southern Medical University
      • Guangzhou, China, 510080
        • The First Affiliated Hospital, Sun Yat-sen University
      • Hefei, China, 12345
        • Anhui Province Cancer Hospital
      • Nanjing, China, 210029
        • Jiangsu Province Hospital (The First Affiliated Hospital with Nanjing Medical University)
      • Shanghai, China, 200032
        • ZhongShan Hospital FuDan University
      • Shanghai, China, 200127
        • Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      • Shenyang, China, 110004
        • Shengjing Hospital Of China Medical University
      • Tianjin, China, 300060
        • Tianjin Cancer Hospital
  • Costa Rica
      • San José, Costa Rica, 10103
        • Clinica CIMCA
      • San José, Costa Rica, 10108
        • ICIMED Instituto de Investigación en Ciencias Médicas
  • Croatia
      • Zagreb, Croatia, 10000
        • Clinical Hospital Centre Zagreb
  • Egypt
      • Cairo, Egypt, 11391
        • AirForce Specialized Hospital
  • Estonia
      • Tallinn, Estonia, 13419
        • North Estonia Medical Centre, Oncology and hematology Clinic
      • Tartu, Estonia, 50406
        • Tartu University Hospital
  • Finland
      • Tampere, Finland, 33520
        • TAYS Radius rakennus
  • France
      • Grenoble, France, 38043
        • CHU Grenoble Sud
      • Lille, France, 59037
        • CHRU de Lille - Hopital Claude Huriez
      • Marseille, France, 13385
        • APHM
      • Montpellier, France, 34295
        • CH Saint Eloi
      • Nantes, France, 44093
        • CHU de Nantes - Hotel Dieu
      • Paris, France, 75571
        • APHP - Hôpital Saint Antoine
      • Pessac, France, 33604
        • CHU Bordeaux
      • Rennes, France, 35042
        • Centre Eugene Marquis;Service d'oncologie
      • Toulouse, France, 31059
        • CHU de Toulouse - Hôpital Rangueil
      • Vandœuvre-lès-Nancy, France, 54511
        • Hopitaux de Brabois - Gastro-Entereologie
      • Villejuif, France, 94804
        • Hopital Paul Brousse
  • Germany
      • Frankfurt, Germany, 60590
        • Klinik Johann Wolfgang von Goethe Uni
      • Hanover, Germany, 30625
        • Med. Hochschule Hannover
      • Mainz, Germany, 55131
        • Uniklinik Mainz
      • Tübingen, Germany, 72076
        • Universität Tübingen
      • Ulm, Germany, 89081
        • Universitatsklinikum Ulm
  • Greece
      • Athens, Greece, 115 27
        • Laiko General Hospital Athen
      • Nea Kifissia, Greece, 14564
        • Agioi Anargiroi Hospital of Kifissia
  • Israel
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus
      • Petah Tikva, Israel, 4941492
        • Rabin Medical Center
      • Tel Aviv, Israel, 6423900
        • Sourasky Medical Center
  • Italy
    • Campania
      • Naples, Campania, Italy, 80131
        • Azienda Osp Uni Seconda Università Degli Studi Di Napoli
      • Naples, Campania, Italy, 80100
        • Fondazione Pascale
      • Naples, Campania, Italy, 80147
        • Ospedale del Mare
    • Emilia-Romagna
      • Bologna, Emilia-Romagna, Italy, 40138
        • A.O. S. Orsola Malpighi
    • Lazio
      • Rome, Lazio, Italy, 00168
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
      • Rome, Lazio, Italy, 00152
        • Azienda Ospedaliera San Camillo Forlanini
    • Lombardy
      • Milan, Lombardy, Italy, 20122
        • Fondazione IRCCS Ospedale Maggiore Policlinico
    • Piedmont
      • Turin, Piedmont, Italy, 10128
        • Azienda Ospedaliera Ordine Mauriziano di Torino
    • Sicily
      • Palermo, Sicily, Italy, 90127
        • A.O.U. Policlinico Paolo Giaccone
    • Tuscany
      • Florence, Tuscany, Italy, 50139
        • Azienda Ospedaliero-Universitaria Careggi
      • Pisa, Tuscany, Italy, 56100
        • Azlenda Ospendaliero-Universitaria Pisana
    • Veneto
      • Padova, Veneto, Italy, 35128
        • IRCCS Istituto Oncologico Veneto (IOV)
  • Japan
      • Aichi, Japan, 470-1192
        • Fujita Health University Hospital
      • Chiba, Japan, 277-8577
        • National Cancer Center Hospital East
      • Fukuoka, Japan, 830-0011
        • Kurume University Hospital
      • Hiroshima, Japan, 734-8551
        • Hiroshima University Hospital
      • Hyōgo, Japan, 670-8540
        • Japanese Red Cross Society Himeji Hospital
      • Kanagawa, Japan, 232-0024
        • Yokohama City University Medical Center
      • Osaka, Japan, 589-8511
        • Kindai University Hospital
      • Osaka, Japan, 565-0871
        • The University of Osaka Hospital
      • Tochigi, Japan, 329-0498
        • Jichi Medical University Hospital
      • Tokyo, Japan, 180-8610
        • Japanese Red Cross Musashino Hospital
  • Malaysia
    • FED. Territory of Kuala Lumpur
      • Kuala Lumpur, FED. Territory of Kuala Lumpur, Malaysia, 59100
        • Uni Malaya Medical Center
      • Putrajaya, FED. Territory of Kuala Lumpur, Malaysia, 62250
        • Institute Kanser Negara (IKN)
  • Philippines
      • Cebu City, Philippines, 6000
        • Cebu Doctors' University Hospital
      • Makati City, Philippines, 1229
        • Makati Medical Center
      • Pasig, Philippines, 1600
        • The Medical City
  • Russia
    • Moscow Oblast
      • Moscow, Moscow Oblast, Russia, 115478
        • FSBI "National Medical Research Center of Oncology N.N. Blokhin?
      • Moscow, Moscow Oblast, Russia, 125134
        • Moscow City Oncology Hospital #62
      • Moskva, Moscow Oblast, Russia, 119991
        • I.M.Sechenov First Moscow State Medical University (1st MSMU)
  • Slovenia
      • Ljubljana, Slovenia, 1000
        • University Medical Center Ljubljana
  • South Korea
      • Goyang-si, South Korea, 10408
        • National Cancer Center
      • Gyeonggi-do, South Korea, 13496
        • CHA Bundang Medical Center
      • Seoul, South Korea, 06351
        • Samsung Medical Center
      • Seoul, South Korea, 03722
        • Severance Hospital, Yonsei University Health System
  • Spain
      • Córdoba, Spain, 14004
        • Hospital Universitario Reina Sofia
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Marañon
      • Madrid, Spain, 28050
        • START Madrid. Centro Integral Oncologico Clara Campal
      • Madrid, Spain, 28027
        • Clinica Universidad de Navarra Madrid
      • Valencia, Spain, 46026
        • Hospital Universitario La Fe
      • Zaragoza, Spain, 50009
        • Hospital Universitario Miguel Servet
    • Balearic Islands
      • Palma de Mallorca, Balearic Islands, Spain, 07198
        • Hospital Son Llatzer
    • LA Coruna
      • Santiago de Compostela, LA Coruna, Spain, 15706
        • Complejo Hospitalario Universitario de Santiago (CHUS)
    • Navarre
      • Pamplona/iruña, Navarre, Spain, 31008
        • Clinica Universitaria de Navarra
  • Switzerland
      • Bern, Switzerland, 3010
        • Inselspital Bern Medizin Gastroenterologie
      • Zurich, Switzerland, 8091
        • Universitätsspital Zürich Medizin Gastroenterologie
  • Taiwan
      • Tainan, Taiwan, 710
        • Chi-Mei Medical Centre
      • Zhongzheng Dist., Taiwan, 10048
        • National Taiwan University Hospital
  • Thailand
      • Bangkok, Thailand, 10330
        • Chulalongkorn Hospital
      • Bangkok, Thailand, 10700
        • Faculty of Med. Siriraj Hosp.
  • Turkey (Türkiye)
      • Ankara, Turkey (Türkiye), 06520
        • Memorial Ankara Hastanesi
      • Bakirkoy / Istanbul, Turkey (Türkiye), 34147
        • Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji
      • Bağcılar, Turkey (Türkiye), 34214
        • Medipol Mega Üniversite Hastanesi Göztepe
      • Bursa, Turkey (Türkiye), 16059
        • Uludag Uni Hospital
      • Istanbul, Turkey (Türkiye)
        • Acibadem Altunizade Hastanesi
      • Izmir, Turkey (Türkiye), 35100
        • Ege Uni Medical Faculty Hospital
      • Sihhiye/Ankara, Turkey (Türkiye), 06230
        • Hacettepe Uni Medical Faculty Hospital
  • United Kingdom
      • Birmingham, United Kingdom, B15 2TH
        • Queen Elizabeth Hospital
      • Liverpool, United Kingdom, L7 8YA
        • The Clatterbridge Cancer Centre NHS Foundation Trust
      • London, United Kingdom, W12 0HS
        • Hammersmith Hospital
      • London, United Kingdom, NW3 2QS
        • Royal Free Hospital
      • London, United Kingdom, SE5 9RS
        • King College Hospital NHS Foundation Trust
      • Manchester, United Kingdom, M2O 4BX
        • Christie Hospital Nhs Trust
      • Newcastle upon Tyne, United Kingdom, NE7 7DN
        • Freeman Hospital
      • Oxford, United Kingdom, OX3 7LE
        • Churchill Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 HCC with diagnosis confirmed by histology/ cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic patients.
  • Disease progression following prior atezolizumab plus bevacizumab combination treatment for HCC, for at least 4 consecutive treatment cycles, and 2 subsequent tumor assessments. It is required that at least 1 tumor assessment shows either stable disease (SD), partial response (PR), or complete response (CR).
  • At least one measurable (per RECIST v1.1) target lesion that has not been previously treated with local therapy or, if the target lesion is within the field of previous local therapy, has subsequently progressed in accordance with RECIST v1.1.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 within 7 days prior to randomization
  • Child-Pugh class A within 7 days prior to randomization
  • Adequate hematologic and end-organ function

Exclusion Criteria:

  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
  • History of leptomeningeal disease
  • History of hepatic encephalopathy, preceding 6 months, unresponsive to therapy within 3 days
  • Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Atezolizumab + Lenvatinib or Sorafenib
Participants will receive atezolizumab plus lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Drug: Atezolizumab
Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Other Names:
  • Tecentriq
Drug: Lenvatinib
Lenvatinib will be administered once daily by mouth each day of every 21-day study treatment cycle. Participants with a baseline body weight of < 60 kg will receive a daily dose of 8 mg. Participants with a baseline body weight of ≥ 60 kg will receive a daily dose of 12 mg.
Drug: Sorafenib
Sorafenib will be administered at a dose of 800 mg per day, i.e. two tablets of 200 mg swallowed by mouth twice daily (equivalent to a total daily dose of 800 mg) each day of every 21-day study treatment cycle.
Active Comparator: Lenvatinib or Sorafenib
Participants will receive lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Drug: Lenvatinib
Lenvatinib will be administered once daily by mouth each day of every 21-day study treatment cycle. Participants with a baseline body weight of < 60 kg will receive a daily dose of 8 mg. Participants with a baseline body weight of ≥ 60 kg will receive a daily dose of 12 mg.
Drug: Sorafenib
Sorafenib will be administered at a dose of 800 mg per day, i.e. two tablets of 200 mg swallowed by mouth twice daily (equivalent to a total daily dose of 800 mg) each day of every 21-day study treatment cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Randomization until death from any cause (approximately 42 months)
Overall survival (OS) is defined as the time from randomization into the study to death from any cause.
Randomization until death from any cause (approximately 42 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: Randomization until the first occurrence of disease progression or death from any cause whichever occurs first (approximately 42 months)
Progression free survival (PFS) is defined as the time from randomization into the study to the first occurrence of disease progression or death from any cause (whichever occurs first).
Randomization until the first occurrence of disease progression or death from any cause whichever occurs first (approximately 42 months)
Confirmed Objective Response Rate (ORR)
Time Frame: Approximately 42 months
Confirmed Objective Response Rate (ORR) is defined as the proportion of patients with a best response of either complete or partial response.
Approximately 42 months
Time to Progression (TTP)
Time Frame: Randomization until the first occurrence of disease progression (approximately 42 months)
Time to Progression (TTP) is defined as the time from randomization to the first occurrence of disease progression.
Randomization until the first occurrence of disease progression (approximately 42 months)
Duration of Response (DOR)
Time Frame: Time from the first occurrence of a confirmed documented objective response to disease progression or death from any cause whichever occurs first (approximately 42 months)
Duration of Response (DOR) is defined as the time from the first occurrence of a documented confirmed objective response to disease progression or death from any cause (whichever occurs first).
Time from the first occurrence of a confirmed documented objective response to disease progression or death from any cause whichever occurs first (approximately 42 months)
Percentage of Participants With Adverse Events
Time Frame: Throughout study duration (approximately 42 months)
Throughout study duration (approximately 42 months)
Percentage of Participants With Adverse Events for Combination Treatment, Adverse Events Related to Atezolizumab, and TKI-Related Adverse Events
Time Frame: Throughtout study (approximately 42 months)
Throughtout study (approximately 42 months)
Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
Time Frame: Throughout study (approximately 42 months)
Throughout study (approximately 42 months)
Serum Concentration of Atezolizumab
Time Frame: At pre-defined intervals from first administration of study drug to approximately 42 months
At pre-defined intervals from first administration of study drug to approximately 42 months
Time to confirmed deterioration (TTCD)
Time Frame: Randomization to first deterioration maintained for two consecutive assessments, or one assessment followed by death from any cause wthin 3 weeks or 6 weeks (approximately 42 months)
Time to confirmed deterioration (TTCD), of health-related quality of life (HRQoL), is defined as the time from randomization to first confirmed deterioration (decrease from baseline of ≥ 10 points) maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks (if Cycle 1-6) or 6 weeks (if after Cycle 6) in the following European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQC30) scales (separately): physical function, role function, and GHS/QoL.
Randomization to first deterioration maintained for two consecutive assessments, or one assessment followed by death from any cause wthin 3 weeks or 6 weeks (approximately 42 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 26, 2021

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2026

Study Registration Dates

First Submitted

February 23, 2021

First Submitted That Met QC Criteria

February 23, 2021

First Posted (Actual)

February 25, 2021

Study Record Updates

Last Update Posted (Actual)

May 14, 2026

Last Update Submitted That Met QC Criteria

May 13, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MO42541

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

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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