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

Keun-Wook Lee, Dae Ho Lee, Jin Hyoung Kang, Joon Oh Park, Se Hyun Kim, Yong Sang Hong, Seung Tae Kim, Do-Youn Oh, Yung-Jue Bang, Keun-Wook Lee, Dae Ho Lee, Jin Hyoung Kang, Joon Oh Park, Se Hyun Kim, Yong Sang Hong, Seung Tae Kim, Do-Youn Oh, Yung-Jue Bang

Abstract

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.

Trial registration: ClinicalTrials.gov NCT02261285 NCT02261298.

© AlphaMed Press; the data published online to support this summary is the property of the authors.

Figures

Figure 1.
Figure 1.
Pharmacokinetics of nivolumab: Mean serum concentration–time profiles of nivolumab after administration of a single intravenous infusion to Korean patients at doses of 1–10 mg/kg. Bars indicate mean ± standard deviation.
Figure 2.
Figure 2.
Pharmacokinetics of nivolumab: Cmax of nivolumab after administration of a single intravenous infusion to Korean patients at doses of 1–10 mg/kg. Bars indicate mean ± standard deviation. Abbreviation: Cmax, maximum serum concentration.
Figure 3.
Figure 3.
Pharmacokinetics of nivolumab: AUC21day of nivolumab after administration of a single intravenous infusion to Korean patients at doses of 1–10 mg/kg. Bars indicate mean ± standard deviation. Abbreviation: AUC21day, areas under serum concentration–time curve from day 0 to day 21 (last measurement).

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Source: PubMed

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