Phase III Study of Rilvegostomig in Combination With Bevacizumab With or Without Tremelimumab as First-line Treatment of Hepatocellular Carcinoma

The purpose of this study is to assess the efficacy and tolerability of rilvegostomig in combination with bevacizumab with or without tremelimumab as first-line treatment in participants with advanced HCC. The study comprises 2 parts - a safety lead-in and a randomised period. Prior to the start of the randomised period of the study, a single-arm safety lead-in period will be applied to evaluate the safety and tolerability of rilvegostomig in combination with bevacizumab and tremelimumab.

Primary Outcome Measures

1. To demonstrate the efficacy of Arm A relative to Arm C by assessment of OS in participants with advanced HCC
   OS is defined as the time from randomisation until the date of death due to any cause.

Secondary Outcome Measures

1. To demonstrate the efficacy of Arm B relative to Arm C by assessment of OS in participants with advanced HCC
   OS is defined as the time from randomisation until the date of death due to any cause.
2. To further demonstrate the efficacy of Arm A relative to Arm C and Arm B relative to Arm C in participants with advanced HCC
   PFS according to RECIST 1.1
3. To further demonstrate the efficacy of Arm A relative to Arm C and Arm B relative to Arm C in participants with advanced HCC
   ORR according to RECIST 1.1
4. To further demonstrate the efficacy of Arm A relative to Arm C and Arm B relative to Arm C in participants with advanced HCC
   DoR according to RECIST 1.1
5. To demonstrate the efficacy of Arm A relative to Arm B in participants with advanced HCC
   OS
6. To demonstrate the efficacy of Arm A relative to Arm B in participants with advanced HCC
   PFS
7. To demonstrate the efficacy of Arm A relative to Arm B in participants with advanced HCC
   ORR
8. To demonstrate the efficacy of Arm A relative to Arm B in participants with advanced HCC
   DoR
9. To demonstrate the efficacy of Arm A relative to Arm C in the population defined by PD-L1 expression subgroups
   Association of PD-L1 expression level with: • OS
10. To demonstrate the efficacy of Arm A relative to Arm C in the population defined by PD-L1 expression subgroups
    Association of PD-L1 expression level with: • PFS per RECIST 1.1
11. To demonstrate the efficacy of Arm A relative to Arm C in the population defined by PD-L1 expression subgroups
    Association of PD-L1 expression level with: • ORR per RECIST 1.1
12. To demonstrate the efficacy of Arm B relative to Arm C in the population defined by PD-L1 expression subgroups
    Association of PD-L1 expression level with: OS
13. To demonstrate the efficacy of Arm B relative to Arm C in the population defined by PD-L1 expression subgroups
    Association of PD-L1 expression level with: PFS per RECIST 1.1
14. To demonstrate the efficacy of Arm B relative to Arm C in the population defined by PD-L1 expression subgroups
    Association of PD-L1 expression level with: ORR per RECIST 1.1
15. To investigate the immunogenicity of Arm A and Arm B
    Presence of ADAs for tremelimumab and rilvegostomig
16. Occurrence of adverse events (AEs) and serious adverse events (SAEs)
    Occurrence of AEs and SAEs will be graded according to the revised NCI CTCAE v5.0.