Associate Principal Scientist Certara, United States
Disclosure(s):
Kimiko McGirr, PhD: No financial relationships to disclose
Antibody-drug conjugates (ADCs) combine the specificity of a targeted antibody with the potency of a cytotoxic payload. While a powerful combination in theory, the opportunity for achieving efficacy without severe toxicity can be quite narrow in practice. This study aims to address challenges in projecting an ADC’s therapeutic window, which include limitations with leveraging preclinical toxicity data and clinical inter- and intra-patient heterogeneity. By explicitly modeling the mechanisms of action of trastuzumab-emtansine (Kadcyla) and sampling physiologically-relevant parameter ranges of metastatic breast cancer patients, this QSP model projects overall response rate and incidence of severe thrombocytopenia, the dose-limiting toxicity. These projections are potentially more predictive than QSP modeling alone. The model can be used to explore alternate dosing regimens to maximize therapeutic index.
