Abstract: Nivolumab is a humanized monoclonal antibody that blocks the programmed death 1 (PD-1) receptor. The initially recommended dose was 3 mg/kg every 2 weeks (Q2W) when nivolumab was firstly approved by the US FDA in 2014. A flat dose of 240 mg Q2W was approved in 2016, and subsequently 480 mg Q4W in 2018. Model-informed drug development (MIDD) approach was applied for the analyses of drug exposure, safety and efficacy based on the data from existed clinical studies, and the model-informed analyses became the key evidences supporting approval of new dosage regimens. Relevant studies and regulatory considerations related to the nivolumab dose selection and subsequent modification were reviewed in this paper. The application of MIDD approach in dose optimization is additionally discussed.

Key words: nivolumab, model-informed drug development, exposure-response relationship, dose optimization