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

Unresectable Hepatocellular Carcinoma Clinical Trial

— IMbrave251  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04770896
• Other study ID #: MO42541
• Status: Recruiting
• Phase: Phase 3
• Start date: April 26, 2021
• Est. completion date: March 31, 2025

Study information

• Verified date: March 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: MO42541 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global.rochegenentechtrials[@]roche.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 systemic treatment with atezolizumab plus bevacizumab combination.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 554
• Est. completion date: March 31, 2025
• Est. primary completion date: September 23, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Unresectable Hepatocellular Carcinoma

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
Austria	Medizinische Universität Innsbruck; Universitätsklinik für Innere Medizin I	Innsbruck
Austria	Uniklinikum Salzburg, LKH; Univ.Klinik f. Innere Medizin III der PMU	Salzburg
Austria	Universitätsklinikum St. Pölten; Innere Medizin 2	St. Pölten
Austria	Klinik Favoriten; Abteilung für Chirurgie	Wien
Belgium	Imeldaziekenhuis	Bonheiden
Belgium	AZ KLINA	Brasschaat
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	Hospital Erasme	Bruxelles
Belgium	UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Belgium	AZ Delta (Campus Rumbeke)	Roeselare
Brazil	Hospital Felicio Rocho	Belo Horizonte	MG
Brazil	Sociedade beneficente de senhoras Hospital Sirio Libanes	Brasilia	DF
Brazil	YNOVA Pesquisa Clinica	Florianopolis	SC
Brazil	Hospital Moinhos de Vento	Porto Alegre	RS
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	Clinicas Oncologicas Integradas - COI	Rio De Janeiro	RJ
Brazil	Hospital Sao Rafael - HSR	Salvador	BA
Brazil	Centro Paulista de Oncologia	Sao Paulo	SP
Brazil	Beneficencia Portuguesa de Sao Paulo	São Paulo	SP
Bulgaria	Multiprofile Hospital for Active Treatment Uni Hospital; Department of medicinal oncology	Panagyurishte
Bulgaria	Complex Oncological Center - Plovdiv, EOOD; Second Internal Department	Plovdiv
Bulgaria	MHAT SofiaMed; OOD	Sofia
Bulgaria	MHAT Sveta Sofia; Department of medical oncology	Sofia
Bulgaria	SHATOD Dr. Marko Antonov Markov-Varna, EOOD; Department of Medicinall Onchotherapy and Palliative	Varna
Canada	Tom Baker Cancer Centre-Calgary	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Chile	Centro de Estudios Clínicos SAGA	Santiago
Chile	Hospital Clinico de La Universidad de Chile J.J.A.; Oncologia	Santiago
Chile	Pontificia Universidad Catolica de Chile; Clinica San Carlos de Apoquindo	Santiago
China	Peking University People's Hospital	Beijing
China	The Fifth Medical Center of People's Liberation Army General Hospital	Beijing City
China	Hunan Cancer Hospital	Changsha CITY
China	Sichuan Provincial Cancer Hospital	Chengdu
China	West China Hospital - Sichuan University	Chengdu City
China	Fujian Provincial Hospital	Fuzhou City
China	Nanfang Hospital, Southern Medical University	Guangzhou
China	Sun Yet-sen University Cancer Center	Guangzhou City
China	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou City
China	Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University	Hangzhou City
China	Harbin Medical University Cancer Hospital	Harbin
China	Anhui Province Cancer Hospital	Hefei City
China	Shandong Cancer Hospital	Jinan
China	Shandong Provincial Hospital	Jinan
China	Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)	Nanjing City
China	Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai
China	Shengjing Hospital of China Medical University	ShenYang
China	Tianjin Cancer Hospital	Tianjin
China	Tongji Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
Costa Rica	Clinica CIMCA	San José
Costa Rica	ICIMED Instituto de Investigación en Ciencias Médicas	San José
Croatia	Clinical Hospital Centre Zagreb	Zagreb
Egypt	AirForce Specialized Hospital; Clinical Oncology	Cairo
Estonia	North Estonia Medical Centre, Oncology and hematology Clinic; Department of Chemotherapy	Tallinn
Estonia	Tartu University Hospital; Clinic of Hematology and Oncology	Tartu
Finland	Docrates Cance Center; Docrates	Helsinki
Finland	TAYS Radius rakennus; onkologinen lääketutkimusyksikkö	Tampere
Finland	Turku Uni Central Hospital; Oncology Clinics	Turku
France	CHU Grenoble Sud; Service hépato-gastroentérologie	GRENOBLE Cedex 9
France	CHRU de Lille - Hopital Claude Huriez	Lille
France	Aphm; Cpcet	Marseille
France	CH Saint Eloi	Montpellier
France	CHU de Nantes - Hotel Dieu	Nantes
France	CHU Nice - Hôpital de l'Archet 2; service Hepato gastro enterologie	Nice Cedex
France	APHP - Hopital Saint Antoine	Paris
France	CHU Bordeaux	Pessac
France	Centre Eugene Marquis; Service d'oncologie; Direction de la Recherche Clinique	Rennes
France	CHU de Toulouse - Hôpital Rangueil	Toulouse Cedex 09
France	Hopitaux de Brabois - Gastro-Entereologie	Vandoeuvre-les-nancy
France	Hopital Paul Brousse; Centre Hepatologie Biliaire	Villejuif
Germany	Klinikum Esslingen; Allg. Innere Med., Onkologie, Hämatologie, Gastroenterologie und Infektiologie	Esslingen
Germany	Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik I	Frankfurt
Germany	Med. Hochschule Hannover; Gastroenterologie	Hannover
Germany	Uniklinik Mainz; I. Medizinische Klinik	Mainz
Germany	Universität Tübingen; Med. Klinik; Innere Medizin I	Tübingen
Germany	Universitätsklinikum Ulm; Zentrum für Innere Medizin Klinik für Innere Medizin I	Ulm
Greece	Laiko General Hospital Athen; Uni Clinic of Gastrenterology	Athens
Greece	Agioi Anargiroi Hospital of Kifissia; University Internal Medicine Clinic	Nea Kifissia
Greece	Anticancer Hospital of Thessaloniki " Theagenio"	Thessaloniki
Greece	Hippokratio Hospital; 4Th Internal Medicine Dpt	Thessaloniki
India	HealthCare Global Enterprises Limited; Medical Oncology	Banglore	Karnataka
India	Tata Memorial Hospital; Dept of Medical Oncology	Mumbai	Maharashtra
Israel	Rambam Health Care Campus; Oncology	Haifa
Israel	Rabin Medical Center; Oncology Dept	Petah Tikva
Israel	Sourasky Medical Center; Oncology Department	Tel-Aviv
Italy	A.O. S. Orsola Malpighi; Ambulatorio Epatocarcinoma (Bolondi)	Bologna	Emilia-Romagna
Italy	Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1	Firenze	Toscana
Italy	Fondazione IRCCS Ospedale Maggiore Policlinico; Gastroenterologia	Milano	Lombardia
Italy	Azienda Osp Uni Seconda Università Degli Studi Di Napoli; Unità Operativa Oncologia Medica	Napoli	Campania
Italy	Fondazione Pascale; U.O. Sperimentazioni Cliniche	Napoli	Campania
Italy	Ospedale del Mare; UOC di Oncologia	Napoli	Campania
Italy	IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda	Padova	Veneto
Italy	A.O.U. Policlinico Paolo Giaccone; Gastroenterologia ed Epatologia	Palermo	Sicilia
Italy	Azlenda Ospendaliero-Universitaria Pisana; C.O. Oncologia 2	Pisa	Toscana
Italy	Azienda Ospedaliera San Camillo Forlanini	Roma	Lazio
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Lazio
Italy	Azienda Ospedaliera Ordine Mauriziano di Torino	Torino	Piemonte
Japan	Fujita Health University Hospital	Aichi
Japan	Chiba University Hospital	Chiba
Japan	National Cancer Center Hospital East	Chiba
Japan	Kurume University Hospital	Fukuoka
Japan	Hiroshima University Hospital	Hiroshima
Japan	Japanese Red Cross Society Himeji Hospital	Hyogo
Japan	Yokohama City University Medical Center	Kanagawa
Japan	Kindai University Hospital	Osaka
Japan	Osaka University Hospital	Osaka
Japan	Jichi Medical University Hospital	Tochigi
Japan	Japanese Red Cross Musashino Hospital	Tokyo
Japan	Toranomon Hospital	Tokyo
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	CHA Bundang Medical Center	Gyeonggi-do
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Malaysia	Uni Malaya Medical Center; Clinical Oncology Unit, Menara Timur	Kuala Lumpur	FED. Territory OF Kuala Lumpur
Malaysia	Beacon International Specialist Centre; Clinical Research Department, Level 2	Petaling Jaya, Selangor	Selangor
Malaysia	Institute Kanser Negara (IKN)	Putrajaya	FED. Territory OF Kuala Lumpur
Philippines	Cebu Doctors' University Hospital; Research Office	Cebu City
Philippines	Makati Medical Center	Makati City
Philippines	The Medical City; Cancer Center	Pasig City
Russian Federation	Chelyabinsk Regional Clinical Oncology Dispensary	Chelyabinsk	Moskovskaja Oblast
Russian Federation	FSBI "National Medical Research Center of Oncology N.N. Blokhin?	Moscow	Moskovskaja Oblast
Russian Federation	Moscow City Oncology Hospital #62; Outpatient Care Center	Moscow	Moskovskaja Oblast
Russian Federation	Group of companies "Medci"	Moskva	Moskovskaja Oblast
Russian Federation	I.M.Sechenov First Moscow State Medical University (1st MSMU)	Moskva	Moskovskaja Oblast
Russian Federation	LLC "Oncology scientific centre"	Pesochny	Sankt Petersburg
Russian Federation	Clinical Hospital Lapino (LLC Haven)	Yudino	Moskovskaja Oblast
Slovenia	University Medical Center Ljubljana; Clinical Dept. of Gastroenterology	Ljubljana
Spain	Hospital Universitari Vall d'Hebron; Servicio de Hepatologia	Barcelona
Spain	Hospital Universitario Reina Sofia; Servicio de Hepatologia	Cordoba
Spain	Clinica Universidad de Navarra Madrid; Servicio de Oncología	Madrid
Spain	Hospital Clinico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Aparato Digestivo	Madrid
Spain	START Madrid. Centro Integral Oncologico Clara Campal; CIOCC	Madrid
Spain	Hospital Son Llatzer; Servicio de Oncologia	Palma de Mallorca	Islas Baleares
Spain	Clinica Universitaria de Navarra; Servicio de Hepatologia	Pamplona/iruña	Navarra
Spain	Corporacio Sanitaria Parc Tauli; Servicio de Hepatologia	Sabadell	Barcelona
Spain	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia	Santiago de Compostela	LA Coruña
Spain	Hospital Universitario la Fe; Servicio de Oncologia	Valencia
Spain	Hospital Universitario Miguel Servet; Servicio Oncologia	Zaragoza
Switzerland	Inselspital Bern Medizin Gastroenterologie	Bern
Switzerland	Universitätsspital Zürich Medizin Gastroenterologie; Klinik für Gastroenterologie und Hepatologie	Zürich
Taiwan	Chi-Mei Medical Centre; Hematology & Oncology	Tainan
Taiwan	National Taiwan University Hospital; Oncology	Zhongzheng Dist.
Thailand	Chulalongkorn Hospital; Medical Oncology	Bangkok
Thailand	Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology	Bangkok
Turkey	Adana Ac?badem Hospital Oncology Department	Adana
Turkey	Memorial Ankara Hastanesi	Ankara
Turkey	Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji	Bakirkoy / Istanbul
Turkey	Uludag Uni Hospital; Oncology	Bursa
Turkey	Medipol Mega Üniversite Hastanesi Göztepe	Istanbul
Turkey	Ege Uni Medical Faculty Hospital; Oncology Dept	Izmir
Turkey	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Sihhiye/Ankara
Turkey	Ac?badem Altunizade Hastanesi; Oncology	Üsküdar
United Kingdom	Queen Elizabeth Hospital; Hepatobiliary Unit	Birmingham
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Liverpool
United Kingdom	Hammersmith Hospital; Clinical trials unit	London
United Kingdom	King College Hospital NHS Foundation Trust	London
United Kingdom	Royal Free Hospital	London
United Kingdom	Christie Hospital Nhs Trust; Medical Oncology	Manchester
United Kingdom	Freeman Hospital; Gastroenterology & Liver Unit	Newcastle Upon Tyne
United Kingdom	Churchill Hospital; Department of Oncology	Oxford

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  China,  Costa Rica,  Croatia,  Egypt,  Estonia,  Finland,  France,  Germany,  Greece,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Philippines,  Russian Federation,  Slovenia,  Spain,  Switzerland,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).	Randomization until the first occurrence of disease progression or death from any cause whichever occurs first (approximately 42 months)
Secondary	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.	Approximately 42 months
Secondary	Time to Progression (TTP)	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)
Secondary	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).	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)
Secondary	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.	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)
Secondary	Percentage of Participants With Adverse Events		Throughout study duration (approximately 42 months)
Secondary	Percentage of Participants With Adverse Events for Combination Treatment, Adverse Events Related to Atezolizumab, and TKI-Related Adverse Events		Throughtout study (approximately 42 months)
Secondary	Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab		Throughout study (approximately 42 months)
Secondary	Serum Concentration of Atezolizumab		At pre-defined intervals from first administration of study drug to approximately 42 months