History of Changes for Study: NCT04770896

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

Latest version (submitted March 20, 2024) on ClinicalTrials.gov

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Study Record Versions

Version	Submitted Date	Changes
1	February 23, 2021	None (earliest Version on record)
2	March 22, 2021	Contacts/Locations, Study Status and Oversight
3	April 13, 2021	Study Status and Contacts/Locations
4	May 13, 2021	Recruitment Status, Contacts/Locations and Study Status
5	May 17, 2021	Contacts/Locations and Study Status
6	June 9, 2021	Contacts/Locations and Study Status
7	July 6, 2021	Contacts/Locations and Study Status
8	July 29, 2021	Contacts/Locations and Study Status
9	August 25, 2021	Contacts/Locations and Study Status
10	September 21, 2021	Contacts/Locations and Study Status
11	October 13, 2021	Contacts/Locations and Study Status
12	November 13, 2021	Contacts/Locations and Study Status
13	December 7, 2021	Contacts/Locations and Study Status
14	December 17, 2021	Contacts/Locations and Study Status
15	January 13, 2022	Study Status and Contacts/Locations
16	February 11, 2022	Contacts/Locations and Study Status
17	March 2, 2022	Contacts/Locations, Study Status, Eligibility, Outcome Measures and Study Description
18	March 28, 2022	Contacts/Locations and Study Status
19	April 18, 2022	Study Status and Contacts/Locations
20	May 17, 2022	Contacts/Locations and Study Status
21	June 14, 2022	Contacts/Locations and Study Status
22	July 8, 2022	Contacts/Locations and Study Status
23	July 29, 2022	Contacts/Locations and Study Status
24	August 1, 2022	Study Status and Eligibility
25	August 25, 2022	Contacts/Locations and Study Status
26	September 23, 2022	Study Status and Contacts/Locations
27	October 23, 2022	Contacts/Locations and Study Status
28	November 21, 2022	Contacts/Locations and Study Status
29	December 19, 2022	Contacts/Locations and Study Status
30	January 18, 2023	Contacts/Locations and Study Status
31	February 17, 2023	Contacts/Locations and Study Status
32	March 24, 2023	Contacts/Locations and Study Status
33	April 27, 2023	Study Status and Contacts/Locations
34	May 26, 2023	Contacts/Locations and Study Status
35	June 22, 2023	Contacts/Locations and Study Status
36	July 17, 2023	Contacts/Locations and Study Status
37	August 14, 2023	Contacts/Locations and Study Status
38	September 13, 2023	Contacts/Locations and Study Status
39	October 13, 2023	Contacts/Locations and Study Status
40	November 9, 2023	Contacts/Locations and Study Status
41	December 7, 2023	Study Status and Contacts/Locations
42	January 5, 2024	Contacts/Locations and Study Status
43	February 2, 2024	Contacts/Locations and Study Status
44	March 20, 2024	Contacts/Locations, Study Status and Outcome Measures

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Study NCT04770896
Submitted Date: February 23, 2021 (v1)

Study Identification


Unique Protocol ID:	MO42541
Brief Title:	A Study of Atezolizumab With Lenvatinib or Sorafenib Versus Lenvatinib or Sorafenib Alone in Hepatocellular Carcinoma Previously Treated With Atezolizumab and Bevacizumab (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
Secondary IDs:

Study Status


Record Verification:	February 2021
Overall Status:	Not yet recruiting
Study Start:	April 12, 2021
Primary Completion:	September 23, 2024 [Anticipated]
Study Completion:	September 23, 2024 [Anticipated]

First Submitted:	February 23, 2021
First Submitted that Met QC Criteria:	February 23, 2021
First Posted:	February 25, 2021 [Actual]

Last Update Submitted that Met QC Criteria:	February 23, 2021
Last Update Posted:	February 25, 2021 [Actual]

Study Description


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

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 3
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	None (Open Label)
Allocation:	Randomized
Enrollment:	554 [Anticipated]

Arms and Interventions

Arms

Assigned Interventions

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

Drug: Sorafenib

Outcome Measures


Primary Outcome Measures:
1.	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.
Secondary Outcome Measures:
1.	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).
2.	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.
3.	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.
4.	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 confirmed documented objective response to disease progression or death from any cause (whichever occurs first).
5.	Time to deterioration (TTD) [ 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 deterioration (TTD) is defined as the time from randomization to first 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.
6.	Percentage of Participants With Adverse Events [ Time Frame: 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 [ Time Frame: Throughtout study (approximately 42 months) ]
8.	Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab [ Time Frame: Throughout study (approximately 42 months) ]
9.	Serum Concentration of Atezolizumab [ Time Frame: At pre-defined intervals from first administration of study drug to approximately 42 months ]

Eligibility


Minimum Age:	18 Years
Maximum Age:	75 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	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, or 2 subsequent tumor assessments, whichever is longer. 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, proceeding 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

Contacts/Locations


Central Contact Person:	Reference Study ID Number: MO42541 www.roche.com/about_roche/roche_worldwide.htm Telephone: 888-662-6728 (U.S. and Canada) Email: global.rochegenentechtrials@roche.com
Study Officials:	Clinical Trials Study Director Hoffmann-La Roche
Locations:	Belgium
	Cliniques Universitaires St-Luc Bruxelles, Belgium, 1200
	UZ Gent Gent, Belgium, 9000
	UZ Leuven Leuven, Belgium, 3000
	Greece
	Laiko General Hospital Athen; Uni Clinic of Gastrenterology Athens, Greece, 115 27
	University General Hospital of Heraklion; Gastroenterology Clinic Heraklion, Greece, 711 10
	Agioi Anargiroi Hospital of Kifissia; University Internal Medicine Clinic Nea Kifissia, Greece, 14564
	Anticancer Hospital of Thessaliniki " Theagenio" Thessaloniki, Greece, 54007
	Hippokratio Hospital; 4Th Internal Medicine Dpt Thessaloniki, Greece, 546 42
	Israel
	Rambam Health Care Campus; Oncology Haifa, Israel, 3109601
	Rabin Medical Center; Oncology Dept Petach Tikva, Israel, 4941492
	Sourasky Medical Center; Oncology Department Tel-Aviv, Israel, 6423900
	Italy, Campania
	Azienda Osp Uni Seconda Università Degli Studi Di Napoli; Unità Operativa Oncologia Medica Napoli, Campania, Italy, 80131
	Italy, Toscana
	Azlenda Ospendaliero-Universitaria Pisana; C.O. Oncologia 2 Pisa, Toscana, Italy, 56100
	Japan
	Chiba University Hospital Chiba, Japan, 260-8677
	Korea, Republic of
	National Cancer Center Goyang-si, Korea, Republic of, 10408
	CHA Bundang Medical Center Gyeonggi-do, Korea, Republic of, 13496
	Samsung Medical Center Seoul, Korea, Republic of, (0)6351
	Severance Hospital, Yonsei University Health System Seoul, Korea, Republic of, 03722
	Spain
	Hospital Universitari Vall d'Hebron; Servicio de Hepatologia Barcelona, Spain, 08035
	Hospital Universitario Reina Sofia; Servicio de Hepatologia Cordoba, Spain, 14004
	Hospital Clinico San Carlos; Servicio de Oncologia Madrid, Spain, 28040
	Hospital Universitario 12 de Octubre; Servicio de Oncologia Madrid, Spain, 28041
	START Madrid. Centro Integral Oncologico Clara Campal; CIOCC Madrid, Spain, 28050
	Hospital Universitario la Fe; Servicio de Oncologia Valencia, Spain, 46026
	Hospital Universitario Miguel Servet; Servicio Oncologia Zaragoza, Spain, 50009
	Spain, Islas Baleares
	Hospital Son Llatzer; Servicio de Oncologia Palma de Mallorca, Islas Baleares, Spain, 07198
	Spain, LA Coruña
	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia Santiago de Compostela, LA Coruña, Spain, 15706
	Spain, Navarra
	Clinica Universitaria de Navarra; Servicio de Hepatologia Pamplona/iruña, Navarra, Spain, 31008
	Turkey
	Adana Acıbadem Hospital Oncology Department Adana, Turkey, 01130
	Memorial Ankara Hastanesi Ankara, Turkey, 06520
	Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji Bakirkoy / Istanbul, Turkey, 34147
	Medipol Mega Üniversite Hastanesi Göztepe Bağcılar, Turkey, 34214
	Acıbadem Altunizade Hastanesi; Oncology Istanbul, Turkey
	Izmir Ataturk Training and Research Hospital Izmir, Turkey, 35965
	Hacettepe Uni Medical Faculty Hospital; Oncology Dept Sihhiye/Ankara, Turkey, 06230

IPDSharing


Plan to Share IPD:	Yes Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here ( https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
	Supporting Information:
	Time Frame:
	Access Criteria:
	URL:

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