{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T02:45:37Z","timestamp":1784688337976,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Anetumab ravtansine, like other ADC drugs, has high inter\u2010patient variability in its pharmacokinetic (PK) and pharmacodynamic (PD) outcomes, which raises concerns about whether current dosing regimens are optimal for patients. The objective of this study was to evaluate covariates, especially body habitus and the innate immune system (IIS), which may affect anetumab ravtansine PK and PD as part of two clinical trials in patients with ovarian cancer and mesothelioma. Biomarkers of Fc\u03b3 receptors(Fc\u03b3R) CD64 on IIS cells, total body weight (TBW), body surface area (BSA), and other covariates, such as sex and age, were analyzed for an association with anetumab ravtansine PK. Higher Fc\u03b3R CD64, TBW, and BSA were associated with higher clearance (CL) of anetumab ravtansine (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). However, there was no relationship between TBW or BSA and Fc\u03b3R CD64. Female patients had a lower anetumab ravtansine CL (0.030\u2009\u00b1\u20090.007\u2009L\/h) compared to male patients (0.042\u2009\u00b1\u20090.006\u2009L\/h) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). In both studies, patients with stable disease (SD) and partial response (PR) had higher anetumab ravtansine AUC<jats:sub>0\u2010inf<\/jats:sub> compared to patients with progressive disease (PD). Individualizing the dose of anetumab ravtansine and potentially other ADCs based only on TBW is not optimal, whereas precision dosing of an ADC based on the inclusion of novel metrics of IIS biomarkers, body habitus, and sex may be more appropriate to reduce variability in PK exposure, reduce toxicity, and improve response.<\/jats:p>","DOI":"10.1111\/cts.70178","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T10:10:07Z","timestamp":1741687807000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Evaluation of Innate Immune System, Body Habitus, and Sex on the Pharmacokinetics and Pharmacodynamics of Anetumab Ravtansine in Patients With Cancer"],"prefix":"10.1111","volume":"18","author":[{"given":"Li","family":"Chen","sequence":"first","affiliation":[{"name":"UNC Eshelman School of Pharmacy, UNC Lineberger Comprehensive Cancer Center, and UNC Advanced Translational Pharmacology 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