Phase I Pharmacokinetic Study of Nivolumab in Korean Patients with Advanced Solid Tumors

LESSONS LEARNED. This pharmacokinetic study of nivolumab showed that there is little ethnic difference in the handling of nivolumab. Nivolumab was well tolerated in Korean patients. BACKGROUND. This phase I study of nivolumab, an anti‐programmed cell death‐1 (anti‐PD‐1) monoclonal antibody, investigated the pharmacokinetics and safety of nivolumab in Korean patients with advanced solid tumors. Findings were compared with results from Japan and the U.S. MATERIALS AND METHODS. In this two‐part study, patients received a single dose of nivolumab (1, 3, and 10 mg/kg; ONO‐4538‐13) and were followed up for 3 weeks. Those who met the required criteria proceeded to the second part (ONO‐4538‐14), and received the same dose as in part one every 2 weeks. RESULTS. Six patients per dose level were enrolled (n = 18). The mean elimination half‐life of nivolumab among the groups ranged from 15.0 to 19.1 days. The maximum serum concentration and area under serum concentration–time curve increased almost dose‐proportionally at doses from 1 to 10 mg/kg. Adverse drug reactions (ADRs; mostly grade ≤2) were reported in seven patients (38.9%). ADRs grade ≥3 occurred in one patient (5.6%; pneumonitis). Three patients (16.7%) developed ADRs related to thyroid dysfunction. CONCLUSION. The pharmacokinetic parameters of nivolumab were similar among patients from Korea, Japan, and the U.S. The safety profile was consistent with findings from previous studies.