Clinical Pharmacology – Biomolecular
Oncology is moving towards treatments with immuno-oncology (I/O) combinations consisting of anti-PD1 monoclonal antibodies (mAbs) such as Keytruda and Opdivo. Optimal dose is a key decision to balance the efficacy and safety in these combinations. Receptor engagement on T cells is the first step driving the efficacy of I/O mAbs. Hence, the dose of I/O mAbs should be driven by receptor properties. However, characterizing intra-tumor receptor engagement is challenging in the clinic due to limitations related to biopsies. To fill this gap, physiologically based pharmacokinetic (PBPK) model can integrate knowledge of mAb distribution and receptor properties to predict intra-tumor receptor engagement.