A Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of BRII-5395 in Combination With Sintilimab and Bevacizumab in Advanced Hepatitis B Virus Related Hepatocellular Carcinoma

An Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of BRII-5395 in Combination With Sintilimab and Bevacizumab in Participants With Advanced Hepatitis B Virus Related Hepatocellular Carcinoma

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced HBV-Related Hepatocellular Carcinoma
• Intervention / Treatment: Drug: BRII-5395; Drug: Sintilimab; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ning Li, Dr.; Phone Number: +8601087788713; Email: lining@cicams.ac.cn
• Study Contact Backup: Name: Shuhang Wang, Dr.; Phone Number: +8613581809307; Email: wangshuhang@cicams.ac.cn

Study Locations

• China
  • Beijing, China
    • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
    • Contact: Ning Li, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BRII-5395 dose escalation; Participants will receive BRII-5395 at protocol-specified dose and schedule, and in combination with sintilimab 200 mg and bevacizumab 15 mg/kg, every 3 weeks. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or loss to follow-up, whichever occurs first.	Drug: BRII-5395; BRII-5395 will be given via IM injection; Drug: Sintilimab; Sintilimab will be given via IV infusion; Drug: Bevacizumab; Bevacizumab will be given via IV infusion
Experimental: BRII-5395 dose expansion; Participants will receive BRII-5395 at a dose level selected from Arm 1, and in combination with sintilimab 200 mg and bevacizumab 15mg/kg, every 3 weeks. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or loss to follow-up, whichever occurs first.	Drug: BRII-5395; BRII-5395 will be given via IM injection; Drug: Sintilimab; Sintilimab will be given via IV infusion; Drug: Bevacizumab; Bevacizumab will be given via IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and type of dose-limiting toxicities (DLTs)	Up to 30 days post last dose
Adverse events (AEs) and serious AEs (SAEs)	Up to 30 days post last dose
Abnormalities in laboratory and other clinical assessments	Up to 30 days post last dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	Up to 2 years
Progression-free survival (PFS)	Up to 2 years
Objective response rate (ORR)	Up to 2 years
Duration of response (DOR)	Up to 2 years
Disease control rat (DCR)	Up to 2 years

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Study Director: Shuhang Wang, Dr., Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: April 7, 2026
• First Submitted That Met QC Criteria: April 23, 2026
• First Posted (Actual): April 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab; sintilimab
• Other Study ID Numbers: BRII-5395-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No