# Applications of Pharmacometrics in Antibody–Drug Conjugate Development

## TL;DR

This review discusses how pharmacometrics can help optimize the development of antibody-drug conjugates for cancer treatment.

## Contribution

The paper provides a comprehensive overview of pharmacometric approaches specific to antibody-drug conjugates.

## Key findings

- ADCs have unique pharmacokinetic profiles due to their structure and deconjugation in circulation.
- Pharmacometric models are essential for understanding exposure-response relationships in ADC development.
- Advanced analytical technology and modeling approaches are urgently needed for ADC optimization.

## Abstract

Antibody–drug conjugates (ADCs), which integrate a cytotoxic drug known as the payload into a tumor-targeting monoclonal antibody via a linker, have emerged as promising candidates for cancer therapy and are a new avenue for targeted cancer therapy. The pharmacokinetic (PK) profiles of ADCs are distinctive due to their unique distribution, catabolism, and elimination. Their deconjugation in circulation and variations in the drug-to-antibody ratio increase the complexity of their PK profiles. Pharmacometric models depicting the PK properties and exposure-response (E-R) relationships of ADCs are important for optimizing dosing regimens and supporting decisions during ADC development. This review considers the PK profiles of ADCs, physiologically based PK models, semi-mechanistic and mechanistic PK models, population PK models, and E-R analyses for dose optimization. The prospects and challenges for ADCs, especially the urgent need for advanced analytical technology and modeling approaches, are also outlined.