Clinical pharmacology strategies in supporting drug development and approval of antibody –drug conjugates in oncology

AbstractAntibody –drug conjugates (ADCs) are important molecular entities in the treatment of cancer. These conjugates combine the target specificity of monoclonal antibodies with the potent anti-cancer activity of small-molecule therapeutics. The complex structure of ADCs poses unique challenges to characterize t he drug’s pharmacokinetics (PKs) and pharmacodynamics (PDs) since it requires a quantitative understanding of the PK and PD properties of multiple different molecular species (e.g., ADC conjugate, total antibody and unconjugated cytotoxic drug). As a result, clinical pharmacology strategy of an AD C is rather unique and dependent on the linker/cytotoxic drug technology, heterogeneity of the ADC, PK and safety/efficacy profile of the specific ADC in clinical development. In this review, we summarize the clinical pharmacology strategies in supporting development and approval of ADCs using the a pproved ADCs as specific examples to illustrate the customized approach to clinical pharmacology assessments in their clinical development.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research