{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T05:46:21Z","timestamp":1786945581420,"version":"build-2736575974"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T00:00:00Z","timestamp":1771113600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"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":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Project Optimus has been reforming the dose selection and optimization paradigm in oncology. In this context, model\u2010informed drug development (MIDD) approaches were utilized to validate the optimal dose selection of 6\u2009mg\/kg every 3\u2009weeks (Q3W) for datopotamab deruxtecan (Dato\u2010DXd) in patients with HR\u2010positive\/HER2\u2010negative breast cancer (HR+\/HER2\u2212 BC). A Tumor Growth Inhibition (TGI)\u2013Progression\u2010Free Survival (PFS) modeling framework was developed to assess the relationship between Dato\u2010DXd PK exposure, tumor dynamics, and PFS, and support virtual trial simulations at different Dato\u2010DXd dose levels. Simulations suggested that Dato\u2010DXd at 6\u2009mg\/kg Q3W provide superior tumor control and improved PFS compared to a lower dose in patients with HR+\/HER2\u2212 BC. This work underscores the importance of integrating advanced modeling techniques into the dose optimization paradigm.<\/jats:p>","DOI":"10.1111\/cts.70493","type":"journal-article","created":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T15:00:31Z","timestamp":1771167631000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Optimal Dosage Justification for Datopotamab Deruxtecan in\n                    <scp>HR<\/scp>\n                    \u2010Positive\/\n                    <scp>HER2<\/scp>\n                    \u2010Negative Breast Cancer Through Model\u2010Informed Drug Development Approaches"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0945-6510","authenticated-orcid":false,"given":"Zoey","family":"Tang","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology AstraZeneca  Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3663-4043","authenticated-orcid":false,"given":"KyoungSoo","family":"Lim","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology AstraZeneca  Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology AstraZeneca  Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Dai","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology AstraZeneca  Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7683-5731","authenticated-orcid":false,"given":"Manjunatha","family":"Munegowda","sequence":"additional","affiliation":[{"name":"Clinical Development, Oncology R&amp;D  Mississauga Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9196-5240","authenticated-orcid":false,"given":"Sabrina","family":"Khan","sequence":"additional","affiliation":[{"name":"Clinical Development, Oncology R&amp;D  Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Xu","sequence":"additional","affiliation":[{"name":"Statistics, Oncology R&amp;D  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Shi","sequence":"additional","affiliation":[{"name":"Statistics, Oncology R&amp;D  Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhuo","family":"Pan","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology, Daiichi Sankyo Inc.  Basking Ridge New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Hong","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology, Daiichi Sankyo Inc.  Basking Ridge New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Ren","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology AstraZeneca  Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavan","family":"Vajjah","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology AstraZeneca  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology AstraZeneca  Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2673-1069","authenticated-orcid":false,"given":"Diansong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology AstraZeneca  Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,15]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"US FDA \u201cOptimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases \u201d(2024)."},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13079"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12542"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201019\u20100287"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.00371"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.21.0807"},{"key":"e_1_2_9_8_1","unstructured":"C.Liu \u201cModel\u2010Informed Analysis During NDA\/BLA Review: Insights From Two FDA Case Reviews. Presented at: FDA\u2010ISoP Public Workshop: Model Informed Drug Development (MIDD) for Oncology Products \u201d(2018) https:\/\/www.fda.gov\/media\/112929\/download."},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.64"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.986"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.45.0973"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535\u20107163.MCT\u201021\u20100206"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.24.00920"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO\u201024\u201001544"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.00059"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13058"},{"key":"e_1_2_9_17_1","volume-title":"Population Pharmacokinetic Analysis of Datopotamab Deruxtecan (Dato\u2010DXd), a TROP2\u2010Targeting Antibody\u2010Drug Conjugate","author":"Peign\u00e9 S. Y. P.","year":"2024"},{"key":"e_1_2_9_18_1","volume-title":"Population Pharmacokinetic and Pharmacodynamic Modelling of Dato\u2010DXd in Patients With Advanced or Metastatic NSCLC","author":"Shuang Liang Y. L.","year":"2022"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.70118"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01909"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO\u201024\u201001349"},{"key":"e_1_2_9_22_1","first-page":"94","volume-title":"Annals of Statistics","author":"Bernard Delyon M. L.","year":"1999"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.14"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1995.10476572"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3495"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01900"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010021\u201004250\u20100"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13007"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248\u2010021\u201000660\u20103"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12064"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010018\u20103587\u20107"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12163"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.52.5733"},{"key":"e_1_2_9_34_1","unstructured":"FDA \u201c761394Orig1s000 MULTI\u2010DISCIPLINE REVIEW \u201dhttps:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2025\/761394Orig1s000MultidisciplineR.pdf."}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70493","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.70493","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70493","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T03:15:18Z","timestamp":1773026118000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1111\/cts.70493"],"URL":"https:\/\/doi.org\/10.1111\/cts.70493","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-07-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70493"}}