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Unresectable Hepatocellular CarcinomaPhase 3IMbrave251NCT04770896

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

A Phase 3 study testing Atezolizumab, Lenvatinib and Sorafenib in people with Unresectable Hepatocellular Carcinoma, run by Hoffmann-La Roche at 124 sites in 28 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Unresectable Hepatocellular Carcinoma
What is being tested?
Atezolizumab, Lenvatinib and Sorafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
557 participants
Where
124 sitesin 28 countries
Study dates
26 Apr 2021to 14 Oct 2026
Phase
Phase 3
Are there results?
Not yet: the study is under way

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

  • 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

Who cannot join

  • 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

Trial locations and contacts

124 sites in 28 countries.

124 sites in 28 countries

Italy12 sites

  • A.O. S. Orsola Malpighi

    Bologna, Emilia-Romagna, 40138

  • Azienda Ospedaliero-Universitaria Careggi

    Florence, Tuscany, 50139

  • Fondazione IRCCS Ospedale Maggiore Policlinico

    Milan, Lombardy, 20122

  • Fondazione Pascale

    Naples, Campania, 80100

  • Azienda Osp Uni Seconda Università Degli Studi Di Napoli

    Naples, Campania, 80131

  • Ospedale del Mare

    Naples, Campania, 80147

  • IRCCS Istituto Oncologico Veneto (IOV)

    Padova, Veneto, 35128

  • A.O.U. Policlinico Paolo Giaccone

    Palermo, Sicily, 90127

  • Azlenda Ospendaliero-Universitaria Pisana

    Pisa, Tuscany, 56100

  • Azienda Ospedaliera San Camillo Forlanini

    Rome, Lazio, 00152

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

    Rome, Lazio, 00168

  • Azienda Ospedaliera Ordine Mauriziano di Torino

    Turin, Piedmont, 10128

Other trials in Italy

France11 sites

  • CHU Grenoble Sud

    Grenoble, 38043

  • CHRU de Lille - Hopital Claude Huriez

    Lille, 59037

  • APHM

    Marseille, 13385

  • CH Saint Eloi

    Montpellier, 34295

  • CHU de Nantes - Hotel Dieu

    Nantes, 44093

  • APHP - Hopital Saint Antoine

    Paris, 75571

  • CHU Bordeaux

    Pessac, 33604

  • Centre Eugene Marquis;Service d'oncologie

    Rennes, 35042

  • CHU de Toulouse - Hôpital Rangueil

    Toulouse, 31059

  • Hopitaux de Brabois - Gastro-Entereologie

    Vandœuvre-lès-Nancy, 54511

  • Hopital Paul Brousse

    Villejuif, 94804

Other trials in France

China10 sites

  • Hunan Cancer Hospital

    Changsha, 410013

  • Fujian Provincial Hospital

    Fuzhou, 350001

  • The First Affiliated Hospital, Sun Yat-sen University

    Guangzhou, 510080

  • Nanfang Hospital, Southern Medical University

    Guangzhou, 510515

  • Anhui Province Cancer Hospital

    Hefei, 12345

  • Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)

    Nanjing, 210029

  • Zhongshan Hospital Fudan University

    Shanghai, 200032

  • Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

    Shanghai, 200127

  • Shengjing Hospital of China Medical University

    Shenyang, 110004

  • Tianjin Cancer Hospital

    Tianjin, 300060

Other trials in China

Japan10 sites

  • Fujita Health University Hospital

    Aichi, 470-1192

  • National Cancer Center Hospital East

    Chiba, 277-8577

  • Kurume University Hospital

    Fukuoka, 830-0011

  • Hiroshima University Hospital

    Hiroshima, 734-8551

  • Japanese Red Cross Society Himeji Hospital

    Hyōgo, 670-8540

  • Yokohama City University Medical Center

    Kanagawa, 232-0024

  • The University of Osaka Hospital

    Osaka, 565-0871

  • Kindai University Hospital

    Osaka, 589-8511

  • Jichi Medical University Hospital

    Tochigi, 329-0498

  • Japanese Red Cross Musashino Hospital

    Tokyo, 180-8610

Other trials in Japan

Spain9 sites

  • Hospital Universitario Reina Sofia

    Córdoba, 14004

  • Hospital General Universitario Gregorio Marañon

    Madrid, 28007

  • Clinica Universidad de Navarra Madrid

    Madrid, 28027

  • START Madrid. Centro Integral Oncologico Clara Campal

    Madrid, 28050

  • Hospital Son Llatzer

    Palma de Mallorca, Balearic Islands, 07198

  • Clinica Universitaria de Navarra

    Pamplona/iruña, Navarre, 31008

  • Complejo Hospitalario Universitario de Santiago (CHUS)

    Santiago de Compostela, LA Coruna, 15706

  • Hospital Universitario la Fe

    Valencia, 46026

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

United Kingdom8 sites

  • Queen Elizabeth Hospital

    Birmingham, B15 2TH

  • The Clatterbridge Cancer Centre NHS Foundation Trust

    Liverpool, L7 8YA

  • Royal Free Hospital

    London, NW3 2QS

  • King College Hospital NHS Foundation Trust

    London, SE5 9RS

  • Hammersmith Hospital

    London, W12 0HS

  • Christie Hospital Nhs Trust

    Manchester, M2O 4BX

  • Freeman Hospital

    Newcastle upon Tyne, NE7 7DN

  • Churchill Hospital

    Oxford, OX3 7LE

Other trials in United Kingdom

Turkey (Türkiye)7 sites

  • Memorial Ankara Hastanesi

    Ankara, 06520

  • Medipol Mega Üniversite Hastanesi Göztepe

    Bağcılar, 34214

  • Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji

    Bakirkoy / Istanbul, 34147

  • Uludag Uni Hospital

    Bursa, 16059

  • Acibadem Altunizade Hastanesi

    Istanbul

  • Ege Uni Medical Faculty Hospital

    Izmir, 35100

  • Hacettepe Uni Medical Faculty Hospital

    Sihhiye/Ankara, 06230

Other trials in Turkey (Türkiye)

Brazil6 sites

  • Hospital Felicio Rocho

    Belo Horizonte, Minas Gerais, 30110-160

  • Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN

    Florianópolis, Santa Catarina, 88020-210

  • Hospital Moinhos de Vento

    Porto Alegre, Rio Grande do Sul, 90035-000

  • Hospital Sao Lucas - PUCRS

    Porto Alegre, Rio Grande do Sul, 90610-000

  • Clinicas Oncologicas Integradas - COI

    Rio de Janeiro, 22290-160

  • Beneficencia Portuguesa de Sao Paulo

    São Paulo, 01321-00

Other trials in Brazil

Belgium5 sites

  • AZ KLINA

    Brasschaat, 2930

  • Hospital Erasme

    Brussels, 1070

  • Cliniques Universitaires St-Luc

    Brussels, 1200

  • UZ Leuven

    Leuven, 3000

  • AZ Delta (Campus Rumbeke)

    Roeselare, 8800

Other trials in Belgium

Germany5 sites

  • Klinik Johann Wolfgang von Goethe Uni

    Frankfurt, 60590

  • Med. Hochschule Hannover

    Hanover, 30625

  • Uniklinik Mainz

    Mainz, 55131

  • Universität Tübingen

    Tübingen, 72076

  • Universitätsklinikum Ulm

    Ulm, 89081

Other trials in Germany

Austria4 sites

  • Medizinische Universität Innsbruck

    Innsbruck, 6020

  • Uniklinikum Salzburg, LKH

    Salzburg, 5020

  • Universitätsklinikum St. Pölten

    Sankt Pölten, 3100

  • Klinik Favoriten

    Vienna, 1100

Other trials in Austria

Canada4 sites

  • Arthur J.E. Child Comprehensive Cancer Center-Calgary

    Calgary, Alberta, T2N 4N2

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Juravinski Cancer Centre

    Hamilton, Ontario, L8V 5C2

  • Princess Margaret Cancer Center

    Toronto, Ontario, M5G 2M9

Other trials in Canada

South Korea4 sites

  • National Cancer Center

    Goyang-si, 10408

  • CHA Bundang Medical Center

    Gyeonggi-do, 13496

  • Severance Hospital, Yonsei University Health System

    Seoul, 03722

  • Samsung Medical Center

    Seoul, 06351

Other trials in South Korea

Israel3 sites

  • Rambam Health Care Campus

    Haifa, 3109601

  • Rabin Medical Center

    Petah Tikva, 4941492

  • Sourasky Medical Center

    Tel Aviv, 6423900

Other trials in Israel

Philippines3 sites

  • Cebu Doctors' University Hospital

    Cebu City, 6000

  • Makati Medical Center

    Makati City, 1229

  • The Medical City

    Pasig, 1600

Other trials in Philippines

Russia3 sites

  • FSBI "National Medical Research Center of Oncology N.N. Blokhin?

    Moscow, Moscow Oblast, 115478

  • Moscow City Oncology Hospital #62

    Moscow, Moscow Oblast, 125134

  • I.M.Sechenov First Moscow State Medical University (1st MSMU)

    Moskva, Moscow Oblast, 119991

Other trials in Russia

Bulgaria2 sites

  • Multiprofile Hospital for Active Treatment Uni Hospital

    Panagyurishte, 4500

  • Complex Oncological Center - Plovdiv, EOOD

    Plovdiv, 4004

Other trials in Bulgaria

Costa Rica2 sites

  • Clinica CIMCA

    San José, 10103

  • ICIMED Instituto de Investigación en Ciencias Médicas

    San José, 10108

Other trials in Costa Rica

Estonia2 sites

  • North Estonia Medical Centre, Oncology and hematology Clinic

    Tallinn, 13419

  • Tartu University Hospital

    Tartu, 50406

Other trials in Estonia

Greece2 sites

  • Laiko General Hospital Athen

    Athens, 115 27

  • Agioi Anargiroi Hospital of Kifissia

    Nea Kifissia, 14564

Other trials in Greece

Malaysia2 sites

  • Uni Malaya Medical Center

    Kuala Lumpur, FED. Territory of Kuala Lumpur, 59100

  • Institute Kanser Negara (IKN)

    Putrajaya, FED. Territory of Kuala Lumpur, 62250

Other trials in Malaysia

Switzerland2 sites

  • Inselspital Bern Medizin Gastroenterologie

    Bern, 3010

  • Universitätsspital Zürich Medizin Gastroenterologie

    Zurich, 8091

Other trials in Switzerland

Taiwan2 sites

  • Chi-Mei Medical Centre

    Tainan, 710

  • National Taiwan University Hospital

    Zhongzheng Dist., 10048

Other trials in Taiwan

Thailand2 sites

  • Chulalongkorn Hospital

    Bangkok, 10330

  • Faculty of Med. Siriraj Hosp.

    Bangkok, 10700

Other trials in Thailand

Croatia1 site

  • Clinical Hospital Centre Zagreb

    Zagreb, 10000

Other trials in Croatia

Egypt1 site

  • AirForce Specialized Hospital

    Cairo, 11391

Other trials in Egypt

Finland1 site

  • TAYS Radius rakennus

    Tampere, 33520

Other trials in Finland

Slovenia1 site

  • University Medical Center Ljubljana

    Ljubljana, 1000

Other trials in Slovenia

About this study

Official title: 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.

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called Tecentriq

    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.

  • LenvatinibDrug

    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.

  • SorafenibDrug

    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.

Study groups in NCT04770896
Study groupRoleWhat they receive
Atezolizumab + Lenvatinib or SorafenibExperimentalParticipants will receive atezolizumab plus lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Receives: Drug: Atezolizumab; Drug: Lenvatinib; Drug: Sorafenib
Lenvatinib or SorafenibActive comparatorParticipants will receive lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Receives: Drug: Lenvatinib; Drug: Sorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival (OS)

    Overall survival (OS) is defined as the time from randomization into the study to death from any cause.

    Measured: Randomization until death from any cause (approximately 42 months)

Secondary outcomes (9)

  1. Progression Free Survival (PFS)

    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).

    Measured: Randomization until the first occurrence of disease progression or death from any cause whichever occurs first (approximately 42 months)

  2. Confirmed Objective Response Rate (ORR)

    Confirmed Objective Response Rate (ORR) is defined as the proportion of patients with a best response of either complete or partial response.

    Measured: Approximately 42 months

  3. Time to Progression (TTP)

    Time to Progression (TTP) is defined as the time from randomization to the first occurrence of disease progression.

    Measured: Randomization until the first occurrence of disease progression (approximately 42 months)

  4. Duration of Response (DOR)

    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).

    Measured: 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)

  5. Time to confirmed deterioration (TTCD)

    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.

    Measured: 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)

  6. Percentage of Participants With Adverse Events

    Measured: Throughout study duration (approximately 42 months)

  7. Percentage of Participants With Adverse Events for Combination Treatment, Adverse Events Related to Atezolizumab, and TKI-Related Adverse Events

    Measured: Throughtout study (approximately 42 months)

  8. Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab

    Measured: Throughout study (approximately 42 months)

  9. Serum Concentration of Atezolizumab

    Measured: At pre-defined intervals from first administration of study drug to approximately 42 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Feb 2021
  2. Study start26 Apr 2021
  3. Primary completion14 Oct 2026 (estimated)
  4. Study completion14 Oct 2026 (estimated)

Resources

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
557 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04770896
Sponsor's protocol ID
MO42541
Acronym
IMbrave251
Status last verified
Aug 2026
First submitted
23 Feb 2021
Last updated
25 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Atezolizumab, Lenvatinib and Sorafenib in people with Unresectable Hepatocellular Carcinoma, run by Hoffmann-La Roche at 124 sites in 28 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 25 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 124 sites in Italy, France, China, Japan, Spain and 23 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) (time frame: Randomization until death from any cause (approximately 42 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04770896.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2026.

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