The Vedotin Antibody-Drug Conjugate Payload Drives Platform-Based Nonclinical Safety and Pharmacokinetic Profiles.

ABSTRACT: Nonclinical safety and pharmacokinetic data for monomethyl auristatin E (MMAE) and 14 vedotin antibody-drug conjugates (ADC) were evaluated to determine patterns of toxicity, consistency of pharmacokinetic results, and species differences between rats and monkeys. Most nonclinical toxicities were antigen-independent, common across ADCs, and included hematologic, lymphoid, and reproductive toxicity related to MMAE pharmacology. Hematologic toxicity was the dose-limiting toxicity (DLT) or predominant toxicity for the majority of vedotin ADCs in both species. Tissue expression of the targeted antigen of an ADC rarely correlated with DLT; only two ADCs had antigen-dependent skin DLTs. For two additional ADCs, antigen-dependent delivery of MMAE in the bone marrow may have exacerbated the antige

SUBMITTER: Neff-LaFord HD 

PROVIDER: S-EPMC11443215 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature