Application of PK-PD modeling 11 and simulation approaches for immuno-oncology drugs

The recent breakthroughs in immunotherapy have made a significant impact on treating a wide range of cancer indications; however, this success has brought about new challenges with critical relevance to the design of optimal dose and dosing regimens both as single-agent therapy and in combination with other cancer drugs. Since the first immune checkpoint inhibitor (ipilimumab) was introduced in clinical practice in 2011, there has been considerable interest in evaluation of the key regulatory mechanisms involved in activation of the immune system while identifying sources of variability in the clinical response to such therapies. Hence, it is evident that application of quantitative approaches can highly enhance knowledge regarding the underlying variables important for designing effective dosing strategies in I-O therapies. This chapter focuses on the application and potential impact of PK-PD modeling on I-O therapy.