Organ-specific Responses to Atezolizumab Plus Bevacizumab in Advanced HCC

Hepatocellular carcinoma (HCC) is one of the most frequent causes of cancer-related deaths globally and in Korea. Many patients diagnosed at advanced stage, and systemic therapy is mainstay of treatment in patients with advanced HCC.

However, immune-checkpoint inhibitor (ICI) monotherapy did not significantly improve overall survival in phase III studies. According to previous retrospective analyses, ICI treatment in advanced HCC showed different organ-specific responses. The intrahepatic HCC was the least responsive organ to ICI treatment. The failure of phase III trials of ICI monotherapy may have been attributed to different organ-specific response pattern of ICIs.

Combination of atezolizumab plus bevacizumab is expected to overcome the immunosuppressive microenvironment of liver and may enhance intrahepatic response of ICI.

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Key information

Conditions

Advanced Hepatocellular Carcinoma Adenocarcinoma Carcinoma Carcinoma, Hepatocellular Digestive System Diseases Digestive System Neoplasms Liver Diseases Liver Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial

Age range

19 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Cha Medical Center

Seongnam-si, Gyeonggi-do, 13496, South Korea

About this study

In a previous retrospective analysis of pembrolizumab treated patients with advanced melanoma and NSCLC, patients with liver metastases showed poorer PFS compared with those without liver metastases with reduced ORR. Similar observations have also been reported in metastatic of triple-negative breast cancer patients, there were no responses in patients with liver metastases. Taken together the results of previous studies, hepatic metastases had reduced response to ICI compared with metastases at other organs, regardless of cancer types.

In addition, ICI treatment in advanced HCC showed different organ-specific responses. The poorer response rate in liver to ICI might be affected by liver-specific immunosuppressive microenvironment (TME). To overcome the unfavorable immunosuppressive TME of the liver, combination strategies are needed to achieve enhanced anti-tumor immune responses or alleviated tumor-associated immunosuppression.

Since the cause of death in most HCC patients was hepatic failure due to intrahepatic HCC or underlying liver cirrhosis, the response rate to ICI of intrahepatic tumor lesions is a crucial factor in determining the overall prognosis of advanced HCC.

Therefore, we hypothesize that combination strategy of atezolizumab plus bevacizumab may increase organ specific response in patients with advanced HCC, and may improve survival outcomes accordingly.

Objectives We hypothesize that combination strategy of atezolizumab plus bevacizumab may increase organ specific response in patients with advanced HCC, and may improve survival outcomes accordingly.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Confirmed HCC pathological or non-invasive assessment according to American Association for the Study of Liver Diseases (AASLD) criteria
ECOG performance status 0 or 1
Patients who received Atezolizumab and Bevacizumab combination therapy as first-line systemic treatment for unresectable HCC
Barcelona Clinic Liver Cancer (BCLC) stage B or C
Child-Pugh class A
Measurable lesion
Adequate hematologic and organ function

Exclusion criteria

History of autoimmune disease
Concomitant anticoagulation at therapeutic doses. Low dose aspirin for
cardio protection is permitted.

Treatment and study plan

atezolizumab plus bevacizumab

Drug

Patients received combination therapy with atezolizumab (Tecentriq) and bevacizumab (Avastin) as first-line systemic treatment for advanced hepatocellular carcinoma.

Other names: Atezolizumab, Bevacizumab

Primary outcomes

Percentage of Lesions With Organ-specific Response

Time frame: From treatment initiation until last follow-up (median 10.1 months)

Organ-specific response will be assessed at the lesion level according to RECIST 1.1 criteria. Up to two target lesions per organ (maximum of five total lesions per patient) will be selected and measured unidimensionally. Complete response (CR) is defined as disappearance of the lesion or lymph node short axis diameter <1.0 cm. Partial response (PR) is defined as ≥30% reduction in lesion size. Progressive disease (PD) is defined as ≥20% increase in lesion size. Stable disease (SD) is defined as neither CR, PR, nor PD. New lesions are recorded in addition to original target lesions to determine the total tumor burden.

Sponsors and collaborators

Lead sponsor

CHA University

Other

Collaborators

Hoffmann-La Roche

Registry information

Official study title

Organ-specific Responses to Atezolizumab Plus Bevacizumab in Patients With Advanced Hepatocellular Carcinoma

Important dates

Study start: 2021
Primary completion: 2022
Study completion: 2023
First posted: Apr 28, 2021
Registry last updated: Dec 12, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed