{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T03:04:15Z","timestamp":1789700655329,"version":"4.0.1"},"reference-count":32,"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":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Semi\u2010mechanistic modeling approaches could be useful for optimal dose selection, and one of the approaches is pharmacokinetic (PK)\/receptor occupancy (RO) model for monoclonal antibodies. This study aimed to develop a semi\u2010mechanistic PK\/RO model of S\u2010531011, a humanized monoclonal antibody against human CCR8 and under development for the treatment of solid tumors, in order to predict human RO values in tumor tissues which are not available in the ongoing clinical study. The model consists of three compartments (central, peripheral, and tumor) and includes four compartments (S\u2010531011, CCR8, and complexes 1\/2 within each compartment). The model parameters were set using available clinical data, non\u2010clinical data, and physiological information. The human PK\/RO model was developed by refinement of a mouse PK\/RO model. The time courses of RO values in the tumor compartment were simulated using the model, together with a conservative condition of slow transfer of S\u2010531011 from blood to the tumor. It was predicted that the RO value in the tumor compartment at 21\u2009days (trough after the third dose after administration of S\u2010531011 80\u2009mg) would be maintained at &gt;\u200990% under typical model assumptions. Under the conservative condition, the RO value in the tumor after administration of S\u2010531011 800\u2009mg would remain at &gt;\u200990%. The developed semi\u2010mechanistic PK\/RO model could predict human RO values of S\u2010531011 in tumor tissues. Under typical model assumptions, simulations suggested the dose range of 80\u2013800\u2009mg of S\u2010531011 every 3\u2009weeks would achieve &gt;\u200990% RO in tumor tissues.<\/jats:p>","DOI":"10.1002\/psp4.70332","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:30:26Z","timestamp":1788431426000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Semi\u2010Mechanistic Modeling of S\u2010531011, a Humanized Anti\u2010\n                    <scp>CCR8<\/scp>\n                    Monoclonal Antibody, for Prediction of\n                    <scp>CCR8<\/scp>\n                    Receptor Occupancy in Human Tumor Tissues"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9455-5638","authenticated-orcid":false,"given":"Daichi","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Pharmacokinetics Shionogi and Co., Ltd.  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4931-5655","authenticated-orcid":false,"given":"Wataru","family":"Nogami","sequence":"additional","affiliation":[{"name":"Laboratory for Drug Discovery and Development Shionogi and Co., Ltd.  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1480-5854","authenticated-orcid":false,"given":"Yudai","family":"Sonoda","sequence":"additional","affiliation":[{"name":"Laboratory for Drug Discovery and Development Shionogi and Co., Ltd.  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5799-1532","authenticated-orcid":false,"given":"Hitomi","family":"Morihara","sequence":"additional","affiliation":[{"name":"Laboratory for Drug Discovery and Development Shionogi and Co., Ltd.  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9569-716X","authenticated-orcid":false,"given":"Takayuki","family":"Katsube","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacokinetics Shionogi and Co., Ltd.  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