Sequential combination with ropeginterferon alfa-2b and anti-PD-1 treatment as adjuvant therapy in HBV-related HCC: a phase 1 dose escalation trial.

BACKGROUND/PURPOSE: Post-operative recurrence is a major clinical challenge with hepatocellular carcinoma (HCC). While currently unapproved, anti-programmed cell death 1 (PD-1) and anti-vascular endothelial growth factor combination adjuvant therapy showed promise. We initiated a phase I trial using sequential treatment with ropeginterferon alfa-2b (ropeg), a novel interferon-based antiviral and antitumor agent, followed by anti-PD-1 therapeutic antibody nivolumab as an adjuvant therapy for hepatitis B virus (HBV)-related HCC.

METHODS: Patients who underwent surgical resection of HBV-related HCC with curative intent received sequential therapy with six doses of ropeg every two weeks at 450 μg, followed by three doses of nivolumab escalating from 0.3 to 0.75 mg/kg every two weeks. Safety, HBV surface antigen (HBsAg) loss or decrease, anti-HBV surface (HBs) antibodies, cancer recurrence, and survival were evaluated.

RESULTS: Fifteen eligible patients were enrolled. Most adverse events (AEs) were mild or moderate and no severe or serious AEs were observed. Alanine transaminase flares, including one grade 3 event as dose-limiting toxicity, were noted in five cases and the final recommended dose for anti-PD1 was determined at 0.75 mg/kg. Interestingly, all five cases had HBsAg clearance or reduction. All patients in the study were alive without cancer recurrence during a median follow-up of 1024 days with six patients surviving > 4 years and three for > 5 years.

CONCLUSIONS: This phase I trial supports the safety and clinical efficacy of sequential treatment with ropeg and nivolumab in post-resection HBV-related HCC. This regimen holds promise for further adjuvant therapy trials in HCC, both HBV-related and other types.