Antibody-drug conjugates (ADCs) are a rapidly growing class of anti-cancer therapeutics, yet regulatory guidance on nonclinical studies remains limited. The ADME characterization of ADCs presents unique challenges and carries potential DDI risks. This article outlines an integrated ADME strategy for ADCs from lead optimization to development, based on our experiences, recommendations from regulatory guidelines, and industry position papers. A decision tree is shared to guide payload bioanalysis, PK and DDI evaluation, and biotransformation studies.

• Comprehensive DMPK Solutions: Our one-stop services cover all stages of ADC development, from PK/bioanalysis to ADME/DDI assessment, tailored to the complex pharmacology of ADCs.
• Case Studies:

1. 1. Investigation of payload release mechanisms for FDA-approved ADC
   2. Validation of preclinical PK parameters using innovative analytical approaches

• Risk Assessment Framework: A decision-tree methodology to evaluate ADC payloads as DDI victims, supporting clinical development and regulatory compliance.

The proposed ADME study strategy and decision tree provide a framework to guide the PK, DDI, and ADME evaluations of major payload-containing components released from ADCs in vitro and present in human plasma. For complete methodology details and implementation case studies, please download the full article.