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

NCT04770896 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: MO42541
• Study Type: interventional
• Target: 557
• Locations: 27 countries
• Sites: 121

Brief 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 systemic treatment with atezolizumab plus bevacizumab combination.

Conditions

Unresectable Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  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 Outcomes (9)

• Progression Free Survival (PFS)

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

• Confirmed Objective Response Rate (ORR)

  Approximately 42 months

• Time to Progression (TTP)

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

• Duration of Response (DOR)

  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)

• Time to confirmed deterioration (TTCD)

  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)

Study Arms (2)

Atezolizumab + Lenvatinib or Sorafenib

EXPERIMENTAL

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; Drug: Lenvatinib; Drug: Sorafenib

Lenvatinib or Sorafenib

ACTIVE COMPARATOR

Participants will receive lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Drug: Lenvatinib; Drug: Sorafenib

Interventions

Atezolizumab DRUG

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.

Also known as: Tecentriq

Atezolizumab + Lenvatinib or Sorafenib

Lenvatinib DRUG

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.

Atezolizumab + Lenvatinib or Sorafenib; Lenvatinib or Sorafenib

Sorafenib DRUG

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.

Atezolizumab + Lenvatinib or Sorafenib; Lenvatinib or Sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (123)

Medizinische Universität Innsbruck

Innsbruck, 6020, Austria

Location

Uniklinikum Salzburg, LKH

Salzburg, 5020, Austria

Location

Universitätsklinikum St. Pölten

Sankt Pölten, 3100, Austria

Location

Klinik Favoriten

Vienna, 1100, Austria

Location

AZ KLINA

Brasschaat, 2930, Belgium

Location

Hospital Erasme

Brussels, 1070, Belgium

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

AZ Delta (Campus Rumbeke)

Roeselare, 8800, Belgium

Location

Hospital Felicio Rocho

Belo Horizonte, Minas Gerais, 30110-160, Brazil

Location

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, 90035-000, Brazil

Location

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

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

Florianópolis, Santa Catarina, 88020-210, Brazil

Location

Clinicas Oncologicas Integradas - COI

Rio de Janeiro, 22290-160, Brazil

Location

Beneficencia Portuguesa de Sao Paulo

São Paulo, 01321-00, Brazil

Location

Multiprofile Hospital for Active Treatment Uni Hospital

Panagyurishte, 4500, Bulgaria

Location

Complex Oncological Center - Plovdiv, EOOD

Plovdiv, 4004, Bulgaria

Location

Arthur J.E. Child Comprehensive Cancer Center-Calgary

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 2M9, Canada

Location

Hunan Cancer Hospital

Changsha, 410013, China

Location

Fujian Provincial Hospital

Fuzhou, 350001, China

Location

The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, 510080, China

Location

Nanfang Hospital, Southern Medical University

Guangzhou, 510515, China

Location

Anhui Province Cancer Hospital

Hefei, 12345, China

Location

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

Nanjing, 210029, China

Location

Zhongshan Hospital Fudan University

Shanghai, 200032, China

Location

Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, 200127, China

Location

Shengjing Hospital of China Medical University

Shenyang, 110004, China

Location

Tianjin Cancer Hospital

Tianjin, 300060, China

Location

Clinica CIMCA

San José, 10103, Costa Rica

Location

ICIMED Instituto de Investigación en Ciencias Médicas

San José, 10108, Costa Rica

Location

Clinical Hospital Centre Zagreb

Zagreb, 10000, Croatia

Location

AirForce Specialized Hospital

Cairo, 11391, Egypt

Location

North Estonia Medical Centre, Oncology and hematology Clinic

Tallinn, 13419, Estonia

Location

Tartu University Hospital

Tartu, 50406, Estonia

Location

TAYS Radius rakennus

Tampere, 33520, Finland

Location

CHU Grenoble Sud

Grenoble, 38043, France

Location

CHRU de Lille - Hopital Claude Huriez

Lille, 59037, France

Location

APHM

Marseille, 13385, France

Location

CHU de Nantes - Hotel Dieu

Nantes, 44093, France

Location

APHP - Hopital Saint Antoine

Paris, 75571, France

Location

CHU Bordeaux

Pessac, 33604, France

Location

Centre Eugene Marquis;Service d'oncologie

Rennes, 35042, France

Location

CHU de Toulouse - Hôpital Rangueil

Toulouse, 31059, France

Location

Hopitaux de Brabois - Gastro-Entereologie

Vandœuvre-lès-Nancy, 54511, France

Location

Hopital Paul Brousse

Villejuif, 94804, France

Location

Klinik Johann Wolfgang von Goethe Uni

Frankfurt, 60590, Germany

Location

Med. Hochschule Hannover

Hanover, 30625, Germany

Location

Uniklinik Mainz

Mainz, 55131, Germany

Location

Universität Tübingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Laiko General Hospital Athen

Athens, 115 27, Greece

Location

Agioi Anargiroi Hospital of Kifissia

Nea Kifissia, 14564, Greece

Location

Rambam Health Care Campus

Haifa, 3109601, Israel

Location

Rabin Medical Center

Petah Tikva, 4941492, Israel

Location

Sourasky Medical Center

Tel Aviv, 6423900, Israel

Location

Fondazione Pascale

Naples, Campania, 80100, Italy

Location

Azienda Osp Uni Seconda Università Degli Studi Di Napoli

Naples, Campania, 80131, Italy

Location

Ospedale del Mare

Naples, Campania, 80147, Italy

Location

A.O. S. Orsola Malpighi

Bologna, Emilia-Romagna, 40138, Italy

Location

Azienda Ospedaliera San Camillo Forlanini

Rome, Lazio, 00152, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio, 00168, Italy

Location

Fondazione IRCCS Ospedale Maggiore Policlinico

Milan, Lombardy, 20122, Italy

Location

Azienda Ospedaliera Ordine Mauriziano di Torino

Turin, Piedmont, 10128, Italy

Location

A.O.U. Policlinico Paolo Giaccone

Palermo, Sicily, 90127, Italy

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, Tuscany, 50139, Italy

Location

Azlenda Ospendaliero-Universitaria Pisana

Pisa, Tuscany, 56100, Italy

Location

IRCCS Istituto Oncologico Veneto (IOV)

Padua, Veneto, 35128, Italy

Location

Fujita Health University Hospital

Aichi, 470-1192, Japan

Location

National Cancer Center Hospital East

Chiba, 277-8577, Japan

Location

Kurume University Hospital

Fukuoka, 830-0011, Japan

Location

Hiroshima University Hospital

Hiroshima, 734-8551, Japan

Location

Japanese Red Cross Society Himeji Hospital

Hyōgo, 670-8540, Japan

Location

Yokohama City University Medical Center

Kanagawa, 232-0024, Japan

Location

The University of Osaka Hospital

Osaka, 565-0871, Japan

Location

Kindai University Hospital

Osaka, 589-8511, Japan

Location

Jichi Medical University Hospital

Tochigi, 329-0498, Japan

Location

Japanese Red Cross Musashino Hospital

Tokyo, 180-8610, Japan

Location

Uni Malaya Medical Center

Kuala Lumpur, FED. Territory of Kuala Lumpur, 59100, Malaysia

Location

Institute Kanser Negara (IKN)

Putrajaya, FED. Territory of Kuala Lumpur, 62250, Malaysia

Location

Cebu Doctors' University Hospital

Cebu City, 6000, Philippines

Location

Makati Medical Center

Makati City, 1229, Philippines

Location

The Medical City

Pasig, 1600, Philippines

Location

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

Moscow, Moscow Oblast, 115478, Russia

Location

Moscow City Oncology Hospital #62

Moscow, Moscow Oblast, 125134, Russia

Location

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

Moskva, Moscow Oblast, 119991, Russia

Location

University Medical Center Ljubljana

Ljubljana, 1000, Slovenia

Location

National Cancer Center

Goyang-si, 10408, South Korea

Location

CHA Bundang Medical Center

Gyeonggi-do, 13496, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Son Llatzer

Palma de Mallorca, Balearic Islands, 07198, Spain

Location

Complejo Hospitalario Universitario de Santiago (CHUS)

Santiago de Compostela, LA Coruna, 15706, Spain

Location

Clinica Universitaria de Navarra

Pamplona/iruña, Navarre, 31008, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Clinica Universidad de Navarra Madrid

Madrid, 28027, Spain

Location

START Madrid. Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

Location

Hospital Universitario la Fe

Valencia, 46026, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Inselspital Bern Medizin Gastroenterologie

Bern, 3010, Switzerland

Location

Universitätsspital Zürich Medizin Gastroenterologie

Zurich, 8091, Switzerland

Location

Chi-Mei Medical Centre

Tainan, 710, Taiwan

Location

National Taiwan University Hospital

Zhongzheng Dist., 10048, Taiwan

Location

Chulalongkorn Hospital

Bangkok, 10330, Thailand

Location

Faculty of Med. Siriraj Hosp.

Bangkok, 10700, Thailand

Location

Memorial Ankara Hastanesi

Ankara, 06520, Turkey (Türkiye)

Location

Medipol Mega Üniversite Hastanesi Göztepe

Bağcılar, 34214, Turkey (Türkiye)

Location

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

Bakirkoy / Istanbul, 34147, Turkey (Türkiye)

Location

Uludag Uni Hospital

Bursa, 16059, Turkey (Türkiye)

Location

Acibadem Altunizade Hastanesi

Istanbul, Turkey (Türkiye)

Location

Ege Uni Medical Faculty Hospital

Izmir, 35100, Turkey (Türkiye)

Location

Hacettepe Uni Medical Faculty Hospital

Sihhiye/Ankara, 06230, Turkey (Türkiye)

Location

Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, L7 8YA, United Kingdom

Location

Royal Free Hospital

London, NW3 2QS, United Kingdom

Location

King College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

Christie Hospital Nhs Trust

Manchester, M2O 4BX, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Interventions

atezolizumab; lenvatinib; Sorafenib

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2021
• First Posted: February 25, 2021
• Study Start: April 26, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

TU (7); GR (2); CA (4); IL (3); RU (3); CR (1); EG (1); GB (8); BR (6); DE (5); PH (3); TW (2); BU (2); KR (4); FR (10); CO (2); IT (12); JP (10); ES (9); CH (2); CN (10); MY (2); SL (1); TH (2); AU (4); BE (5); FI (1)