Comparative clinical pharmacokinetics of antibody-drug conjugates in first-in-human Phase 1 studies

Abstract

Although there are currently more than 30 antibody-drug conjugates (ADC) in clinical development for the treatment of blood cancers and solid tumors, comparison of their clinical pharmacokinetics (PK) is challenging because of the large number of, and differences between, the targets, ADC constructs, dosing regimens, and patient populations. In this review, we standardized the evaluation, using non-compartmental PK data reported at Cycle 1, i.e., following the first drug administration of what is usually a repeated-dose treatment, in monotherapy. We report ADC clinical PK properties, dosing regimen, determination of doses ranges and associated maximum tolerated doses. We also evaluated the effect of structural characteristics and target types (hematological vs. solid tumors) on PK. In addition, we discuss how integration of PK/pharmacodynamics approaches on top of classical dose escalation in first-in-human studies may improve dosing regimen determination for subsequent phases of clinical development.

Keywords: :

• antibody-drug conjugates
• dose selection
• dosing regimen
• maximum tolerated dose
• pharmacokinetics
• oncology
• phase I

10.4161/mabs.28965

Disclosure of Potential Conflicts of Interest

The author is full-time employee of Sanofi.

Acknowledgments

The author thanks the following individuals for their review and feedback on this manuscript: F. Donat, N. Fagniez, G. Sanderink, A. Bousseau, and C. Ribard.