{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:20:08Z","timestamp":1787664008230,"version":"build-2736575974"},"reference-count":16,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"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":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Population pharmacokinetic (PK) and exposure\u2013response analyses were performed to characterize the PK and exposure\u2013response relationships of vepdegestrant, a first\u2010in\u2010class, oral PROteolysis\u2010TArgeting Chimera estrogen receptor degrader. Population PK and exposure\u2013response analyses for safety utilized data from the first\u2010in\u2010human study (ARV\u2010471\u2010mBC\u2010101, NCT04072952) and the registrational VERITAC\u20102 study (NCT05654623), which included patients with ER\u2010positive, human epidermal growth factor receptor 2 (HER2)\u2010negative advanced breast cancer. Safety endpoints of clinical interest were evaluated using logistic regression and included grade \u22653 treatment\u2010emergent adverse events (TEAEs) and TEAEs of any grade (arthralgia, fatigue, nausea, aspartate aminotransferase or alanine aminotransferase elevations, anemia, and neutrophil count decreased). Exposure\u2013efficacy analysis included patients with estrogen receptor\u20101 (ESR1)\u2010mutated, ER\u2010positive, HER2\u2010negative advanced breast cancer from the VERITAC\u20102 vepdegestrant arm only. Progression\u2010free survival (PFS) as assessed by blinded independent central review, the primary efficacy endpoint in VERITAC\u20102, was assessed via Cox proportional hazards modeling. Vepdegestrant PK was described by a two\u2010compartment model with linear elimination and sequential zero\u2010, first\u2010order absorption. None of the evaluated covariates significantly influenced the disposition of vepdegestrant. There was no statistically significant relationship between vepdegestrant exposure and any of the evaluated safety endpoints across 30\u2010500 mg total daily doses. In patients with ESR1\u2010mutated, ER\u2010positive, HER2\u2010negative advanced breast cancer treated with vepdegestrant 200 mg once daily in the VERITAC\u20102 study, exposure was not a statistically significant predictor of PFS. Overall, integrated analyses adequately characterized the PK of vepdegestrant, with no clinically meaningful covariate effects. No exposure\u2013response relationships were identified between vepdegestrant exposure and efficacy or safety outcomes.<\/jats:p>","DOI":"10.1002\/jcph.70252","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T04:53:25Z","timestamp":1786337605000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetics and Exposure\u2013Response Analyses of Vepdegestrant, a First\u2010in\u2010Class PROteolysis\u2010TArgeting Chimera Estrogen Receptor Degrader"],"prefix":"10.1002","volume":"66","author":[{"given":"Derek Z.","family":"Yang","sequence":"first","affiliation":[{"name":"Pfizer Inc San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2492-764X","authenticated-orcid":false,"given":"Joanna C.","family":"Masters","sequence":"additional","affiliation":[{"name":"Pfizer Inc San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hechuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Pfizer Inc San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9696-3164","authenticated-orcid":false,"given":"Lana","family":"Tran","sequence":"additional","affiliation":[{"name":"Pfizer Inc San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7221-9277","authenticated-orcid":false,"given":"Yuanyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Arvinas Operations, Inc.  New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly C.","family":"Lee","sequence":"additional","affiliation":[{"name":"Pfizer Inc Groton CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8915-1152","authenticated-orcid":false,"given":"Weiwei","family":"Tan","sequence":"additional","affiliation":[{"name":"Pfizer Inc San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8489-0375","authenticated-orcid":false,"given":"Brian","family":"Jermain","sequence":"additional","affiliation":[{"name":"Pfizer Inc San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010021\u201000371\u20106"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.06.026"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2011.03.031"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2022.103861"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2505725"},{"key":"e_1_2_10_7_1","unstructured":"VEPPANU (Vepdegestrant): Prescribing Information.Pfizer Inc.2026. Accessed July 9 2026.https:\/\/veppanu.com"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318\u2010026\u201001018\u2010w"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538\u20107445.SABCS23\u2010PO3\u201005\u201008"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928\u2010016\u20109487\u20108"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928\u2010017\u20109542\u20100"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248\u2010009\u20109133\u20100"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-04898-2_161"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471722146"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147\u2010024\u201002648\u20103"},{"key":"e_1_2_10_16_1","article-title":"A phase 1, open\u2010label study evaluating the pharmacokinetics, safety, and tolerability of vepdegestrant in Chinese patients with ER+\/HER2\u2010 advanced breast cancer","author":"Xu B","journal-title":"Cancer Chemother Pharmacol"},{"key":"e_1_2_10_17_1","unstructured":"JohnsonTR TranL BaumanJN et\u00a0al.Absorption metabolism excretion and pharmacokinetics of [14C]vepdegestrant in healthy adult participants. Poster presented at:International Society for the Study of Xenobiotics (ISSX) Meeting. September 21\u201024 2025; Chicago IL. Poster P109."}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70252","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70252","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70252","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:33:36Z","timestamp":1787661216000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":16,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/jcph.70252"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70252","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2026-05-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70252"}}