Predictive Biomarkers in Patients With Advanced Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab

Study Overview
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Brief Summary
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The goal of this observational study is to learn about in patients with advanced hepatocellular carcinoma treated with atezoliozumab and bevacizumab. In this clinical study, we intend to analyze the multiomics data by analyzing the peripheral blood and tumor tissue before and after treatment of patients with advanced liver cancer receiving systemic drug treatment, and analyzing the correlation with the treatment. This is an exploratory study that aims to discover biomarkers that are highly correlated with treatment response.

Detailed Description
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Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide, and HCC is more frequently observed in Asia, including South Korea. As HCC is often accompanied by chronic hepatitis B or C virus and liver cirrhosis, treatment of HCC consider not only the tumor but also various factors such as liver function and the patient's performance status. Local treatment and surgery are possible in the early stages of HCC. However, it has a high recurrence rate even after curative surgeries due to underlying cirrhosis and the tumor microenvironment. Although several studies have investigated gene mutations and differences in treatment response in advanced HCC through next-generation sequencing (NGS), studies on transcriptome analysis of advanced HCC through RNA-sequencing are hard to find, with a need for future research into precise classification and clinical significance of HCC based on multi-omics data to establish multi-omics data and discover biomarkers highly associated with treatment response in HCC patients who received atezolizumab and bevacizumab combination.

Official Title
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Investigation of Predictive Biomarkers in Patients With Advanced Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab

Conditions
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Advanced Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: atezolizumab plus bevacizumab


Participation Criteria
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Eligibility Criteria
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The following two groups will be integrated and analyzed. The criteria for both groups are the same. Group 1. Prospective Group Inclusion Criteria Those above the age of 20 who understand the purpose of the study and agree to participate in the collection of samples during the study. Patients who have been diagnosed with unresectable advanced HCC through imaging, histological, or cytological tests. Patients who underwent an NGS test with advanced HCC tissues Patients planning to receive atezolizumab and bevacizumab combination therapy Patients with measurable lesions based on RECIST v1.1 ECOG performance status 0 or 1 Patients with a life expectancy of at least three months Exclusion Criteria Patients who have systemic conditions accompanied by instability of vital signs, such as infections or organ failure Those with mental/neurological conditions or dementia who have difficulties understanding and completing the consent form Those who are assessed as not suitable for this study, at the discretion of the researcher Group 2. Retrospective Group Inclusion Criteria Those above the age of 20 who understand the purpose of the study and agree to participate in the collection of samples during the study. Patients who have been diagnosed with unresectable advanced HCC through imaging, histological, or cytological tests. Patients who underwent an NGS test with advanced HCC tissues Patients have received atezolizumab and bevacizumab combination therapy Patients with measurable lesions based on RECIST v1.1 ECOG performance status 0 or 1 Patients with a life expectancy of at least three months Exclusion criteria Patients who have systemic conditions accompanied by instability of vital signs, such as infections or organ failure Those with mental/neurological conditions or dementia who have difficulties understanding and completing the consent form Those who are assessed as not suitable for this study, at the discretion of the researcher

Ages Eligible for Study
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Minimum Age: 19 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| analytic group<br>advanced HCC Patients | Drug: atezolizumab plus bevacizumab<br>* 1200 mg of atezolizumab plus 15 mg/kg of body weight of bevacizumab intravenously every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| collected tumor samples | tumor samples from patients with hepatocellular carcinoma (incidence of analysis of the expression patterns of various immune response-related proteins through H&E staining, immunochemical staining, and immunofluorescent staining methods, association with treatment response and survival duration) | through study completion, an average of 3 years | 
| collected blood samples | blood samples from patients with hepatocellular carcinoma (incidence of Flow cytometry, ELISA analysis, single cell RNA sequencing, association with treatment response and survival duration | through study completion, an average of 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multi-omics analysis | Multi-omics analysis to further subtype and find therapeutic targets of HCC Multi-omics analysis is a total and integrated analysis of various molecular levels such as dielectric and protein. | 3 years | 
| Biomarkers on the efficacy of Atezolizumab+Bevacizumab for advanced HCC | Molecular biomarker associated with overall survival, progression-free survival and objective response rate in patients who receive atezolizumab plus bevacizumab A gene-based biomarker that predicts the therapeutic response of patients administered with Atezolizumab and Bevacizumab. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular carcinoma