A Study of Atezolizumab in Combination With Bevacizumab in Spanish Patients With Unresectable or Unsuitable for Locoregional Treatments Hepatocellular Carcinoma Not Previously Treated With Systemic Therapy

Study Overview
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Brief Summary
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This is a Phase IIIb, one arm, multicenter, open-label study primarily designed to evaluate the safety of atezolizumab + bevacizumab in participants with unresectable or unsuitable for locoregional treatments for metastatic HCC not previously treated with systemic therapy. As part of its secondary objectives, this study is also designed to evaluate the efficacy of atezolizumab and bevacizumab in these participants.

Official Title
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A Phase IIIb, Single Arm, Multicenter Study of Atezolizumab in Combination With Bevacizumab to Investigate Safety and Efficacy in Spanish Patients With Unresectable or Unsuitable for Locoregional Treatments Hepatocellular Carcinoma Not Previously Treated With Systemic Therapy

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: Atezolizumab
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology or radiologically, following the AASLD criteria Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and /or locoregional therapies No prior systemic therapy (including systemic investigational agents) for HCC At least one measurable (per RECIST 1.1) untreated lesion detected by CT scan Patients who received prior local therapy such as radiofrequency ablation, percutaneous ethanol or acetic acid injection, cryoablation, high-intensity focused ultrasound, transarterial chemoembolization, transarterial embolization (excluding transarterial radioembolization.) are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST version 1.1 Exclusion Criteria: Active or history of autoimmune disease or immune deficiency History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC Co-infection of HBV and HCV

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (atezolizumab plus bevacizumab)<br>Participants will receive Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. | Drug: Atezolizumab<br>* Atezolizumab will be administered intravenously at a dose of 1200 mg on Day 1 of each 21-day cycle.<br>* Other names: Tecentriq;Drug: Bevacizumab<br>* Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle.<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Discontinuations of Atezolizumab and/or Bevacizumab Due to Adverse Events of Grade ≥ 3 |  | Initiation fo study treatment up to approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from initiation of study treatment to death from any cause. | Initiation of study treatment to death from any cause (up to approximately 3 years) | 
| Severity of Adverse Events According to NCI CTCAE v5.0 | The adverse event severity grading scale for the NCI CTCAE (v5.0) will be used for assessing adverse event severity. | Initiation of study treatment up to approximately 3 years | 
| Progression Free Survival (PFS) | PFS is defined as the time from initiation of study treatment 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. | Initiation of study treatment to first occurrence of disease progression or death from any cause (whichever occurs first)(up to approximately 3 years) | 
| Time to Progression (TTP) | Time to progression (TTP) is defined as the time from initiation of study treatment to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1 criteria. | Initiation of study treatment to first occurrence of disease progression (up to approximately 3 years) | 
| Duration of Response (DOR) | Duration of Response (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 the investigator according to RECIST v1.1. | Documented objective response to disease progression or death from any cause (whichever occurs first)(up to approximately 3 years) | 
| Number/Rate of Participants Starting Second Line Treatment |  | Up to approximately 3 years | 
| International Normalized Ratio (INR) |  | Up to approximately 3 years | 
| Presence of Absence of Ascites and/or Hepatic Encephalopathy |  | Up to approximately 3 years | 
| Albumin-Bilirubin (ALBI) Assessment Grades of 1 to 3 | Albumin-Bilirubin Assessment Grades of 1 to 3 based on ALBI score calculation. | Up to approximately 3 years |