Atezolizumab Plus Bevacizumab Alone or Combined with External Beam Radiotherapy for HCC with Macrovascular Invasion

A total of 138 subjects are randomly assigned to one of two treatment groups (69 patients in the atezolizumab+bevacizumab group and 69 patients in the Atezolizumab plus Bevacizumab combined EBRT group).

• Radiotherapy combination:

• Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21day cycle.
• Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21day cycle.
• The external beam radiotherapy will commence after day 2 of the first cycle of Atezolizumab+Bevacizumab, and will be delivered in accordance with institutional protocol.
• Atezolizumab+Bevacizumab:

• Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21day cycle.
• Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21day cycle.

Additional study identifiers: This study was also registered on the WHO's International Clinical Trials Registry Platform, CRIS, before the first participant was enrolled (ID: KCT0007365, Date of registration: 2022-06-08).

Inclusion criteria

• Older than 19 years of age, lower than 80 years of age
• Child-Pugh class A hepatic function
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
• Patients with HCC [diagnosed according to AASLD guidelines] invading the intrahepatic vascular system
• No prior systemic therapy for HCC
• At least one measurable HCC lesion with ≥ 1cm diameter
• Adequate hematologic and organ function

• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count ≥ 1,000 /mm3
• Platelet ≥ 50,000/ mm3 without transfusion
• Total bilirubin ≤ 2.5 mg/dL

Exclusion criteria

• Treatment history of prior systemic treatment of HCC
• Liver transplant recipients
• Patients with peptic ulcer, untreated or incompletely treated varices with bleeding or high-risk for bleeding
• Any serious illness (e.g., active infection or inflammatory condition) or uncontrolled severe medical comorbidity
• A history of treated malignancy (other than HCC) is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding two years
• Abdominal/pelvic radiotherapy within 28 days prior to initiation of study treatment, except palliative radiotherapy to bone lesions within 7 days prior to initiation of study treatment