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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Atezolizumab
* Drug: Becavizumab
* Device: Transarterial chemoembolization (TACE)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: atezolizumab + bevacizumab + TACE<br>Participants will receive atezolizumab plus bevacizumab on Day 1 of a 21-Day cycle, after every on-demand transarterial chemoembolization procedure. | Drug: Atezolizumab<br>* 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.<br>* Other names: Tecentriq;Drug: Becavizumab<br>* Bevacizumab will be administered by IV infusion at a fixed dose of 15 mg/kg on Day 1 of each 21-day Cycle.<br>* Other names: Avastin;Device: Transarterial chemoembolization (TACE)<br>* TACE will be performed by clinical demand.<br>|
| Active Comparator: Arm B: TACE alone<br>Participants will receive on-demand transarterial chemoembolization. | Device: Transarterial chemoembolization (TACE)<br>* TACE will be performed by clinical demand.<br>|

What is the study measuring?
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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 |