{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:51:50Z","timestamp":1791971510621,"version":"4.3.4"},"reference-count":19,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Gotistobart is an investigational, next\u2010generation, humanized IgG1 monoclonal antibody targeting cytotoxic T\u2010lymphocyte antigen\u20104. It is engineered to preserve cytotoxic T\u2010lymphocyte antigen\u20104 through endosomal recycling while enhancing intratumoral regulatory T\u2010cell depletion. A population pharmacokinetic model was developed to characterize gotistobart pharmacokinetics and identify covariates contributing to inter\u2010individual variability in patients with advanced solid tumors. Serum concentration\u2010time data were obtained from 632 patients enrolled in three phase I\u2013III clinical trials. In total, 3406 pharmacokinetic observations across a dose range from 0.1 to 10 mg\/kg were collected. A two\u2010compartment model with linear elimination best described the data, with inter\u2010individual variability on clearance, central volume, and peripheral volume. Parameter estimates were precise, with typical values of 0.005 L\/h for clearance, 0.021 L\/h for inter\u2010compartmental clearance, 2.59 L for central volume, and 3.43 L for peripheral volume. Covariates identified in the model included body weight and albumin on clearance and volumes, and sex on volumes, with limited clinically relevant impact. The model was evaluated using parameter precision, goodness\u2010of\u2010fit diagnostics, and prediction\u2010corrected visual predictive checks. The model was used to simulate concentration\u2010time profiles for clinically relevant dosing regimens. Simulations demonstrated the expected steady\u2010state pharmacokinetic behavior, with dose\u2010dependent increases in peak and trough concentrations. Compared with 6 mg\/kg every 3 weeks, administration of two 10 mg\/kg loading doses followed by 6 mg\/kg every 3 weeks accelerated the attainment of steady state. The validated population pharmacokinetic model provides a quantitative foundation for subsequent exposure\u2010response analyses and regimen selection.<\/jats:p>","DOI":"10.1002\/jcph.70275","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:11:41Z","timestamp":1788419501000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population pharmacokinetics for the CTLA\u20104 modulator gotistobart in patients with advanced solid tumors"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7422-3520","authenticated-orcid":false,"given":"Tianhong","family":"Li","sequence":"first","affiliation":[{"name":"UC Davis Comprehensive Cancer Center  Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2369-0779","authenticated-orcid":false,"given":"Jiahui","family":"Xue","sequence":"additional","affiliation":[{"name":"Wisdom Lake Academy of Pharmacy Xi'an Jiaotong\u2010Liverpool University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"OncoC4 Inc.  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