This early phase (Phase 1) study will evaluate BRII 5395, administered in combination with two approved anticancer agents, sintilimab and bevacizumab, in patients with advanced liver cancer caused by chronic hepatitis B virus (HBV) infection. The primary objective of the study is to assess the safety and tolerability of the combination therapy, as well as to explore preliminary evidence of clinical benefit.

Inclusion Criteria:

1. Diagnosis of locally advanced or metastatic HCC that is deemed unsuitable for surgical resection or transplant.
2. BCLC stages Intermediate (B) or Advanced (C).
3. Failed at least first-line systemic therapy, including ICIs; and disease is not amenable to curative surgical and/or locoregional therapies.
4. Adequate bone marrow and organ function status.
5. Life expectancy > 3 months.
6. HBsAg > 0.05 IU/mL at screening.

Exclusion Criteria:

1. Any systemic anticancer therapy within specified period prior to the first dose of study treatment.
2. Any localized anticancer therapy within specified period prior to the first dose of study treatment.
3. History of anaphylactic hypersensitivity prior to the first dose of study treatment.
4. Known hypersensitivity to polyethylene glycol or any component of sintilimab or bevacizumab formulation, or any contraindications to sintilimab or bevacizumab.
5. Presence of cancer or metastasis in the central nervous system with clinical symptoms.
6. Remaining ≥ NCI-CTCAE grade 2 toxicities from previous anticancer therapy, unless otherwise specified.
7. Current or past history of infection with HIV, HCV, or active tuberculosis.