O22 Efficacy and safety of serplulimab, a novel anti-programmed death-1 antibody, in chronic hepatitis B patients

Introduction

As estimated by the World Health Organization, 296 million people were living with chronic hepatitis B (CHB) in 2019, with 0.82 million hepatitis B-related deaths mostly due to cirrhosis and hepatocellular carcinoma (HCC). In CHB patients, upregulation of programmed death-1 (PD-1) protein is associated with T-cell exhaustion and difficulty in viral clearance. Serplulimab is a novel humanised anti-PD-1 monoclonal antibody that has shown promising antitumour efficacy and manageable safety in several tumour types, including HCC. Here we report the efficacy and safety of serplulimab in CHB patients.

Methods

This was an open-label, multicentre, exploratory phase 2 study (NCT04133259). Patients with CHB were sequentially enrolled following Simon's two-stage optimal design and received up to 3 doses of intravenous serplulimab 1 mg/kg every 4 weeks. Stage 1 planned to enrol 17 patients. If ≤1 response was observed, the study would be stopped; otherwise, an additional 27 subjects would be accrued in stage 2, resulting in a total sample size of 44. The primary endpoint was the proportion of patients achieving 0.5 log decline in hepatitis B surface antigen (HBsAg) log₁₀ IU/mL from baseline to 12 weeks after the last dose of serplulimab. Secondary endpoints included the proportion of patients achieving 1 log decline in HBsAg log₁₀ IU/mL from baseline to 24 weeks after the last dose, the proportion of patients achieving HBsAg loss at 24 weeks after the last dose, and safety.

Results

Between November 2019 and July 2021, 14 patients were screened with 8 eligible for enrolment. All enrolled patients received 3 doses of serplulimab and had HBsAg assessments within 24 weeks after the last dose, and thus were all included in the efficacy and safety analysis population. One patient achieved ≥0.5 log decline in HBsAg log₁₀ from 4 to 24 weeks after the last dose. No patient had ≥1 log decline in HBsAg log₁₀ during the study. Seven (87.5%) patients achieved HBsAg decline at 24 weeks after the last dose. Three (37.5%) patients experienced treatment-emergent adverse events that were possibly related to the study drug, most commonly arthralgia (25%). One (12.5%) patient had immune-related adverse events (arthralgia and back pain). No death or serious adverse event was reported.

Conclusions

Serplulimab 1 mg/kg administered every 4 weeks for up to 3 doses was well tolerated in CHB patients. Although this exploratory study was terminated early due to sponsor decision, the preliminary efficacy observed supports further investigations of serplulimab for CHB patients in clinical settings.