A Study of Durvalumab or Tremelimumab Monotherapy, or Durvalumab in Combination With Tremelimumab or Bevacizumab in Advanced Hepatocellular Carcinoma

This is a multicenter, open-label, stratified, randomized study to evaluate the safety, tolerability, antitumor activity, pharmacokinetics, pharmacodynamics, and immunogenicity of durvalumab or tremelimumab monotherapy, or durvalumab in combination with tremelimumab or bevacizumab in advanced hepatocellular carcinoma.

Inclusion Criteria: 1. Male or female participants 2. 18 years and older (Japan-20 years and older) 3. Confirmed hepatocellular carcinoma (HCC) based on histopathological findings from tumor tissues. Advanced HCC with diagnosis confirmed pathologically or with noninvasive methods. 4. Immunotherapy-naïve 5. Have either progressed on, are intolerant to, or refused treatment with sorafenib or another approved TKI. For arm 5 only: Have not received any prior systemic therapy for HCC. Exclusion Criteria: 1. Prior exposure to immune-mediated therapy 2. Hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy 3. Gastrointestinal bleeding (eg, esophageal varices or ulcer bleeding) within 12 months 4. Ascites requiring non-pharmacologic intervention (eg, paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose. 5. Main portal vein thrombosis (Vp4) as documented on imaging 6. Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment 7. Active or prior documented autoimmune or inflammatory disease with some exceptions 8. Current or prior use of immunosuppressive medication within 14 days with some exceptions