2.2. Phase I Clinical Study
toxicities, DLTs
CANCER RECURRENCE
A Phase I study was conducted to determine the maximum tolerated dose (MTD). A total of 12 eligible patients were enrolled in Cohorts 1 and 2 (The mean age and standard deviation of the eligible patients were 61.8 and 10.3 years, respectively (Dose-limiting toxicities (DLTs) were observed in one patient. Drug-related grade 3 ALT and AST increases were observed in one patient in Cohort 1. The patient completed the ropeginterferon alfa-2b treatment and received one dose of nivolumab. No DLTs were observed in Cohort 2. However, given that the DLTs of grade 3 ALT and AST increases were observed in Cohort 1 and that there were greater levels of grade 2 ALT and AST increases in Cohort 2, we determined that Cohort 2 reached the MTD of the study based on the overall safety assessment. Therefore, six doses of ropeginterferon alfa-2b at 450 ug followed by three doses of nivolumab at 0.75 mg/kg were determined to be the MTD for the adjuvant sequential combination therapy.To date, all patients are alive without cancer recurrence. The mean follow-up period was 716.75 days (minimum, 114 days; maximum, 1416 days). HBsAg was undetectable in one patient in Cohort 1 at follow-up week 12 and after (