To determine the efficacy and safety of atezolizumab-bevacizumab combination therapy plus stereotactic body radiotherapy(SBRT) in patients with advanced hepatocellular carcinoma, Subjects will start SBRT for one or more primary cancers and/or metastatic lesions and no more than 5 sites within two month before and after the start date of atezolizumab-bevacizumab combination therapy.

In this study, it is expected to improve the treatment response rate of atezolizumab-bevacizumab therapy, which is currently first-line chemotherapy but has a low treatment response rate.

The subjects with advanced hepatocellular carcinoma who are indicated for the first-line atezolizumab-bevacizumab combination therapy are the primary subjects, and if they voluntarily agree to the clinical trial after explanation of the clinical trial, they are included in the clinical trial. Subjects should begin SBRT(stereotactic body radiotherapy) to one or more but not more than five sites for primary cancer and/or metastatic lesions within two month before and after the start date of atezolizumab-bevacizumab combination therapy.

The followings are evaluation items for each visit.

Visit 1 (-6~0 weeks) ± 7days *Screening

• Informed consent form
• Inclusion Criteria/ Exclusion Criteria
• Medical history and physical examination
• Staging via CT, MRI, PET-CT, etc. (PET-CT examination is not compulsory)
• CBC, SMA, PT/aPTT, Tumor markers, Biomarkers
• Stool microbiota NGS
• QoL Questionnaire(EORTC-QLQ-C30 V3)

Visit 2 (0~7 weeks) ± 7 days *During SBRT

• Confirmation of adverse events
• QoL Questionnaire(EORTC-QLQ-C30 V3)

Visit 3 (1~8 weeks) *1 week after SBRT

• Confirmation of adverse events
• CBC, SMA, PT/aPTT, Tumor markers, Biomarkers
• QoL Questionnaire(EORTC-QLQ-C30 V3)

Visit 4 (6~9 weeks) ± 7 days *After 2 cycles of chemotherapy

• Confirmation of adverse events
• CBC, SMA, PT/aPTT, Tumor markers, Biomarkers
• Stool microbiota NGS
• QoL Questionnaire(EORTC-QLQ-C30 V3)

Visit: 5~12 (3~36 months) ± 2 weeks *Follow-up

• Confirmation of adverse events
• Evaluation of effectiveness* (Imaging tests, Tumor markers, CBC, SMA, PT/aPTT are performed according to the need)
• QoL Questionnaire(EORTC-QLQ-C30 V3)

Inclusion Criteria:

1. Age 19 to 80 years old
2. Liver function Child-Pugh class A
3. ECOG 0-1
4. Patient clinically or pathologically diagnosed with hepatocellular carcinoma
5. Advanced hepatocellular carcinoma that is inoperable
6. Satisfies the dose limits for normal organs and lesions of an appropriate size to be included in the scope of radiotherapy.

Exclusion Criteria:

1. Brain metastases
2. Have a history of malignancy other than hepatocellular carcinoma within the last 5 years (except for malignancies with little risk of metastasis or death, e.g., adequately treated cervical carcinoma in situ, non-melanoma skin cancer, localized prostate cancer, tubular carcinoma in situ, or stage 1 uterine cancer.)
3. Subjects with a high probability of untreated gastric or esophageal varices or bleeding
4. Serious uncontrolled medical comorbidities
5. History of liver transplant surgery
6. Autoimmune liver disease

Patients with advanced hepatocellular carcinoma who are indicated for the first-line atezolizumab-bevacizumab combination chemotherapy should begin stereotactic body radiotherapy to one or more but not more than five sites for primary cancer and/or metastatic lesions.