Pharmacokinetic/pharmacodynamic relationship of therapeutic monoclonal antibodies used in oncology: Part 1, monoclonal antibodies, antibody-drug conjugates and bispecific T-cell engagers. (March 2020) - Paci, Angelo
Abstract: More than 25 therapeutic monoclonal antibodies (mAbs) used in oncology have been approved since 1997. Their nature has been largely modified through the last 20 years, from the chimeric IgG1 rituximab with pharmacokinetic parameters specific of murin or chimeric mAbs to humanized or human mAbs. Doses and administration frequency have been chosen based on this nature. More recently, the developed and registered mAbs are mostly IgG1, IgG2, IgG3 or IgG4 humanized or 100% human. Therefore, their behavior is different from the first mAbs authorized leading to lower systemic clearance and shorter half-life due to higher cellular uptake balanced by FcRn recognition with recirculation. The complexity of the pharmacokinetics and the pharmacokinetics/pharmacodynamics relation are increased for antibody-drug conjugates or bispecific T-cell engagers. However, significant number of studies reported pharmacokinetics/pharmacodynamics relations, with positive exposure-response link justifying the exploration of the pharmacokinetics in routine clinical practice of these therapeutic mAbs to prevent treatment failures and to limit their toxicities. Highlights: Most of the monoclonal antibodies (mAbs) used in oncology have a pharmacokinetic/pharmacodynamic (PK/PD) relationship. Antibody–drug conjugates also have a PK/PD relationship. PK/PD relation is complex as it includes PK of the cytotoxic, the mAb and the ADC. PK/PD data regarding bispecific antibodies are still lacking. Therapeutic drug monitoring and dose-adjustment may be of interest for some of these drugs.