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.

The study will comprise of 6 parts. Participants in Part 1A (safety run-in cohort), Part 1B (efficacy-gating cohort), Part 2A, and Part 4 will receive weight-based dosing regimens; and participants in Part 2B and Part 3 will receive fixed dosing regimens. Part 1A Stage 2 of the study may start after the first 3 participants in Stage 1 have been observed on study for at least 4 weeks. In addition, a separate cohort of participants will be enrolled in mainland China (China cohort) once global recruitment in Part 2A will be closed. * In Part 1 (both 1A and 1B), participants will receive tremelimumab 1 mg/kg intravenous (IV) every 4 weeks (Q4W) 4 doses and durvalumab 20 mg/kg Q4W. * In Part 2A, participants will be randomized in a 1:1:1 ratio to receive: * Durvalumab 20 mg/kg Q4W * Tremelimumab 10 mg/kg Q4W × 7 doses followed by every 12 weeks (Q12W) * Tremelimumab 1 mg/kg Q4W × 4 doses + durvalumab 20 mg/kg Q4W, followed by durvalumab 20 mg/kg Q4W * In China cohort, Part 2A study design will be followed. * In Part 2B, participants will receive tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W. * In Part 3, participants will be randomized in a 2:2:1:2 ratio to receive: * Durvalumab 1500 mg Q4W * Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W * Tremelimumab 750 mg Q4W for 7 doses followed by Q12W * Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W, followed by durvalumab 1500 mg Q4W. Following protocol amendment 5, enrollment into 'Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg' arm will close. Participants will be randomized at a ratio of 2:1:2 in 'Durvalumab 1500 mg Q4W', 'Tremelimumab 750 mg Q4W for 7 doses followed by Q12W', and 'Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W' arms, respectively. • In Part 4, participants will receive durvalumab 1120 mg (15 mg/kg) + bevacizumab 15 mg/kg every 3 weeks (Q3W). Participants will receive the treatment until confirm progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. All participants will be followed for survival until the end of study visit (last participant discontinues the study treatment).