A Study 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).