A Study of TACE Combined With Atezolizumab Plus Bevacizumab or TACE Alone in Patients With Untreated Heaptocellular Carcionma

A Phase III, Open-Label, Randomized Study of On-Demand TACE Combined With Atezolizumab Plus Bevacizumab (Atezo/Bev) or On-Demand TACE Alone in Patients With Untreated Heaptocellular Carcionma

This study will evaluate the efficacy and safety of atezolizumab plus bevacizumab combined with on-demand TACE compared to on-demand TACE alone in participants with hepatocellular carcinoma who are at high risk of poorer outcome following TACE treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Atezolizumab; Drug: Becavizumab; Device: Transarterial chemoembolization (TACE)

• Study Type: Interventional
• Enrollment (Actual): 342
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui, China, 230001
    • Anhui Provincial Hospital
  • Beijing, China, 100044
    • Peking University People's Hospital
  • Beijing, China, 100034
    • Peking University First Hospital
  • Beijing, China, 102218
    • Beijing Tsinghua Changgung Hospital
  • Beijing, China, 100069
    • Beijing You An Hospital
  • Changsha, China, 410013
    • Hunan Cancer Hospital
  • Chengdu, China
    • West China Hospital, Sichuan University
  • Chongqing, China, 400016
    • The First Affiliated Hospital, Chongqing Medical University
  • Chongqing, China, 400038
    • Southwest Hospital , Third Military Medical University
  • Fuzhou, China, 350014
    • Fujian Cancer Hospital
  • Fuzhou, China, 110016
    • The 900th Hospital of PLA joint service support force
  • Fuzhou, China, 350005
    • The First Affiliated Hospital Of Fujian Medical University
  • Fuzhou, China, 350025
    • Mengchao Hepatobiliary Hospital Of Fujian Medical University
  • Guangzhou, China, 510060
    • Sun Yet-sen University Cancer Center
  • Guangzhou, China, 510515
    • Nanfang Hospital, Southern Medical University
  • Hangzhou, China, 310022
    • Zhejiang Cancer Hospital
  • Harbin, China, 150081
    • Harbin Medical University Cancer Hospital
  • Nanjing, China, 210009
    • Jiangsu Cancer Hospital
  • Nanjing, China, 210029
    • Jiangsu Province Hospital (The First Affiliated Hospital with Nanjing Medical University)
  • Nanning, China, 530021
    • The First Affiliate Hospital of Guangxi Medical University
  • Nanning, China, 530021
    • Guangxi Cancer Hospital of Guangxi Medical University
  • Shanghai, China, 200120
    • Fudan University Shanghai Cancer Center
  • Shanghai, China, 200127
    • Renji Hospital Shanghai Jiaotong University School of Medicine
  • Shanghai, China
    • Zhongshan Hospital Fudan Unvierstiy
  • Shenyang, China, 110004
    • Shengjing Hospital of China Medical University
  • Tianjin, China, 300060
    • Tianjin Cancer Hospital
  • Xi'an, China
    • The First Affiliated Hospital of Xi'an Jiaotong University
  • Xi'an, China
    • Xi'an Inernational Medical Center Hospital
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital
  • Zhuhai, China, 519099
    • Zhuhai People's Hospital
• Japan
  • Aichi, Japan, 464-8681
    • Aichi Cancer Center
  • Chiba, Japan, 260-8677
    • Chiba University Hospital
  • Fukuoka, Japan, 830-0011
    • Kurume University Hospital
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital
  • Kanagawa, Japan, 241-8515
    • Kanagawa Cancer Center
  • Kanagawa, Japan, 252-0375
    • Kitasato University 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
  • Tokyo, Japan, 105-8470
    • Toranomon Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed diagnosis of HCC by histology/ cytology or clinical criteria
• Eligible for TACE treatment
• No prior systemic therapy for HCC, especially immunotherapy
• No prior locoregional therapy to the target lesion(s)
• At least one measurable untreated lesion
• ECOG Performance Status of 0-1
• Child-Pugh class A

Exclusion Criteria:

• Evidence of Vp3/4 and hepatic vein tumor thrombus (HVTT)
• Evidence of extrahepatic spread (EHS)
• Being a candidate for curative treatments
• Any condition representing a contraindication to TACE as determined by the investigators
• Active or history of autoimmune disease or immune deficiency
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding
• A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
• Evidence of bleeding diathesis or significant coagulopathy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: atezolizumab + bevacizumab + TACE; Participants will receive atezolizumab plus bevacizumab on Day 1 of a 21-Day cycle, after every on-demand transarterial chemoembolization procedure.	Drug: Atezolizumab; Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle until participant experience loss of clinical benefit as evaluated by the investigator or unacceptable toxicity or withdrawal of informed consent.; Other Names: Tecentriq; Drug: Becavizumab; Bevacizumab will be administered by IV infusion at a fixed dose of 15 mg/kg on Day 1 of each 21-day Cycle.; Other Names: Avastin; Device: Transarterial chemoembolization (TACE); TACE will be performed by clinical demand.
Active Comparator: Arm B: TACE alone; Participants will receive on-demand transarterial chemoembolization.	Device: Transarterial chemoembolization (TACE); TACE will be performed by clinical demand.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TACE Progression-Free Survival (TACE PFS) as Determined by Investigator	TACE PFS is defined as the time from randomization to untreatable progression or TACE failure/refractoriness or any cause of death, whichever occurs first, as determined by the investigator (INV).	Randomization to untreatable progression or TACE failure/refractoriness or death (up to approximately 46 months)
Overall Survival (OS)	Overall survival (OS) after enrollment is defined as the time from randomization to death from any cause.	Randomization to death from any cause (up to approximately 94 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Untreatable (unTACEable) Progression (TTUP) as Determined by Investigator	INV-assessed TTUP is defined as time from randomization to untreatable (unTACEable) progression, as determined by investigator.	Randomization to untreatable (unTACEable) progression (up to approximately 46 months)
Time to Progression (TTP) as Determined by Investigator	INV-assessed TTP is defined as the time from randomization to unTACEable progression or TACE failure/refractoriness (as defined above), as determined by investigator.	Randomization to unTACEable progression or TACE failure/refractoriness (up to approximately 46 months)
Time to Extrahepatic Spread (EHS) as Determined by Investigator	INV-assessed time to EHS is defined as the time from randomization to the first evidence of EHS, as determined by investigator.	Randomization to first evidence of EHS (up to approximately 46 months)
Objective Response Rate (ORR), as Determined by Investigator	Objective response (OR) is defined as a complete or partial response, as determined by investigator.	Randomization up to approximately 46 months
Duration of Responses (DOR) as Determined by Investigator	INV-assessed DOR is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by INV.	First occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first)(up to approximately 46 months)
Time to Deterioration (TTD)	TTD is defined as the time from randomization to first deterioration in the patient-reported GHS/QoL, physical function, or role function scales of the EORTC QLQ-C30, maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks.	Randomization to first deterioration (up to approximately 94 months)
Percentage of Participants With Adverse Events		Baseline up to approximately 94 months
Progression Free Survival (PFS)	Progression free survival (PFS) is defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.	Randomization to first occurrence of disease progression or death from any cause (whichever occurs first)(up to approximately 94 monthsJ)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2021
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: January 14, 2021
• First Submitted That Met QC Criteria: January 14, 2021
• First Posted (Actual): January 15, 2021

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab; atezolizumab
• Other Study ID Numbers: ML42612

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