{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:10:23Z","timestamp":1789013423198,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"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":["Clin Pharma and Therapeutics"],"abstract":"<jats:p>\n                    Enfortumab vedotin is a nectin\u20104\u2010directed antibody\u2013drug conjugate currently approved in combination with pembrolizumab for the first\u2010line treatment of locally advanced or metastatic urothelial cancer. Here we describe the exposure\u2013response relationship between enfortumab vedotin exposures and efficacy\/safety endpoints in patients who received \u22651 dose of enfortumab vedotin 1.25\u2009mg\/kg (on days 1 and 8 of a 21\u2010day dosing cycle) plus pembrolizumab (recommended dosage) and had evaluable pharmacokinetics in the EV\u2010103 (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009121) and EV\u2010302 (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009432) studies. Overall, most patients were older (median age of 69\u2009years), White (74%), and male (77%), with median body weight in EV\u2010103 (79\u2009kg) trending higher than that in EV\u2010302 (75\u2009kg). Higher exposures of enfortumab vedotin were associated with consistently higher objective response rates across all exposure quartiles in both studies, and longer survival than chemotherapy in EV\u2010302. Increased and faster incidence of treatment\u2010related adverse events (Grade\u2009\u2265\u20093 hyperglycemia, Grade\u2009\u2265\u20093 skin reactions, and Grade\u2009\u2265\u20092 peripheral neuropathy) was also observed with increased exposures. However, dose modifications were effective in managing most adverse events, with most patients having at least partial resolution (hyperglycemia, &gt;75%; skin reactions, &gt;85%; and peripheral neuropathy, &gt;50%). Responses attained with higher early cycle exposure were not impacted by subsequent dose modifications. Overall, exposure\u2013response analysis supports the use of enfortumab vedotin at a starting dose of 1.25\u2009mg\/kg and in combination with pembrolizumab for first\u2010line treatment of locally advanced or metastatic urothelial cancer.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70466","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:59:21Z","timestamp":1789012761000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exposure\u2013Response Analysis of Enfortumab Vedotin Plus Pembrolizumab as First\u2010Line Therapy for Locally Advanced or Metastatic Urothelial Cancer"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6309-214X","authenticated-orcid":false,"given":"Vaishali L.","family":"Chudasama","sequence":"first","affiliation":[{"name":"Pfizer Inc  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Kastrissios","sequence":"additional","affiliation":[{"name":"QuanTx Consulting  Mountain View California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2745-2811","authenticated-orcid":false,"given":"Hossam","family":"Kadry","sequence":"additional","affiliation":[{"name":"Pfizer Inc  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1646-094X","authenticated-orcid":false,"given":"Daping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Pfizer Inc  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salaheldin","family":"Hamed","sequence":"additional","affiliation":[{"name":"Astellas Pharma  Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivasu","family":"Poondru","sequence":"additional","affiliation":[{"name":"Astellas Pharma  Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souvik","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Astellas Pharma  Northbrook Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russ","family":"Wada","sequence":"additional","affiliation":[{"name":"QuanTx Consulting  Mountain View California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4553-9216","authenticated-orcid":false,"given":"Amit","family":"Garg","sequence":"additional","affiliation":[{"name":"Pfizer Inc  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0607-7247","authenticated-orcid":false,"given":"Yen Lin","family":"Chia","sequence":"additional","affiliation":[{"name":"BeOne Medicines  San Carlos California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.1158\/0008-5472.CAN-15-1313","article-title":"Enfortumab vedotin antibody\u2010drug conjugate targeting Nectin\u20104 is a highly potent therapeutic agent in multiple preclinical cancer models","volume":"76","author":"Challita\u2010Eid P.M.","year":"2016","journal-title":"Cancer Res."},{"key":"e_1_2_11_2_1","unstructured":"Prescribing information PADCEV\u00ae (enfortumab vedotin\u2010ejfv)<https:\/\/labeling.pfizer.com\/ShowLabeling.aspx?id=20630>. Accessed August 3 2026."},{"key":"e_1_2_11_3_1","volume-title":"FDA Grants Regular Approval to Enfortumab Vedotin\u2010Ejfv for Locally Advanced or Metastatic Urothelial Cancer","author":"U.S. Food and Drug Administration","year":"2021"},{"key":"e_1_2_11_4_1","volume-title":"FDA Approves Enfortumab Vedotin\u2010Ejfv with Pembrolizumab for Locally Advanced or Metastatic Urothelial Cancer","author":"U.S. Food and Drug Administration","year":"2023"},{"key":"e_1_2_11_5_1","first-page":"875","article-title":"Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer","volume":"390","author":"Powles T.","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"e_1_2_11_6_1","unstructured":"Pfizer Inc. Astellas Pharma Inc.Pfizer and Astellas' PADCEV\u00ae (enfortumab vedotin\u2010ejfv) plus KEYTRUDA\u00ae (pembrolizumab) shows long\u2010term efficacy in first\u2010line treatment of locally advanced or metastatic urothelial cancer (la\/mUC)<https:\/\/www.businesswire.com\/news\/home\/20250210184062\/en\/Pfizer\u2010and\u2010Astellas\u2010PADCEV\u2010enfortumab\u2010vedotin\u2010ejfv\u2010plus\u2010KEYTRUDA\u2010pembrolizumab\u2010Shows\u2010Long\u2010Term\u2010Efficacy\u2010in\u2010First\u2010Line\u2010Treatment\u2010of\u2010Locally\u2010Advanced\u2010or\u2010Metastatic\u2010Urothelial\u2010Cancer\u2010lamUC?utm_campaign=shareaholic&utm_medium=copy_link&utm_source=bookmark>. Accessed October 16 2025."},{"key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"216","DOI":"10.6004\/jnccn.2024.0024","article-title":"Bladder cancer, version 3.2024","volume":"22","author":"Flaig T.W.","year":"2024","journal-title":"J. Natl. Compr. Canc. Netw."},{"key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.annonc.2024.03.001","article-title":"ESMO clinical practice guideline interim update on first\u2010line therapy in advanced urothelial carcinoma","volume":"35","author":"Powles T.","year":"2024","journal-title":"Ann. Oncol."},{"key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1002\/cpt.3383","article-title":"Population pharmacokinetic modeling and exposure\u2010response analysis for the antibody\u2010drug conjugate enfortumab vedotin in locally advanced or metastatic urothelial carcinoma","volume":"116","author":"Zuo P.","year":"2024","journal-title":"Clin. Pharmacol. Ther."},{"issue":"16","key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"4503","DOI":"10.1200\/JCO.2024.42.16_suppl.4503","article-title":"Impact of exposure on outcomes with enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer","volume":"42","author":"Petrylak D.P.","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1200\/JCO.22.01643","article-title":"Enfortumab vedotin plus pembrolizumab in previously untreated advanced urothelial cancer","volume":"41","author":"Hoimes C.J.","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"e_1_2_11_12_1","doi-asserted-by":"crossref","first-page":"4107","DOI":"10.1200\/JCO.22.02887","article-title":"Enfortumab vedotin with or without pembrolizumab in cisplatin\u2010ineligible patients with previously untreated locally advanced or metastatic urothelial cancer","volume":"41","author":"O'Donnell P.H.","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1200\/JCO.19.02044","article-title":"EV\u2010101: a phase I study of single\u2010agent enfortumab vedotin in patients with Nectin\u20104\u2010positive solid tumors, including metastatic urothelial carcinoma","volume":"38","author":"Rosenberg J.","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"e_1_2_11_14_1","doi-asserted-by":"crossref","DOI":"10.1002\/jcph.70241","article-title":"Evaluating the impact of enfortumab vedotin dose modifications on clinical efficacy using tumor growth inhibition modeling in patients with advanced urothelial cancer","volume":"66","author":"Chudasama V.L.","year":"2026","journal-title":"J. Clin. Pharmacol."},{"key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1111\/bcp.16128","article-title":"Time\u2010varying brentuximab vedotin pharmacokinetics and weight\u2010based dosing in paediatric patients despite lower exposure in those aged 2 to <6 and 6\u201311\u2009years","volume":"90","author":"Zhang D.","year":"2024","journal-title":"Br. J. Clin. Pharmacol."},{"key":"e_1_2_11_16_1","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1200\/JCO.19.01140","article-title":"Pivotal trial of enfortumab vedotin in urothelial carcinoma after platinum and anti\u2010programmed death\u20101\/programmed death\u2010ligand 1 therapy","volume":"37","author":"Rosenberg J.E.","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"e_1_2_11_17_1","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/S1470-2045(21)00094-2","article-title":"Enfortumab vedotin after PD\u20101 or PD\u2010L1 inhibitors in cisplatin\u2010ineligible patients with advanced urothelial carcinoma (EV\u2010201): a multicentre, single\u2010arm, phase 2 trial","volume":"22","author":"Yu E.Y.","year":"2021","journal-title":"Lancet Oncol."},{"key":"e_1_2_11_18_1","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1016\/S1470-2045(17)30616-2","article-title":"First\u2010line pembrolizumab in cisplatin\u2010ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE\u2010052): a multicentre, single\u2010arm, phase 2 study","volume":"18","author":"Balar A.V.","year":"2017","journal-title":"Lancet Oncol."},{"key":"e_1_2_11_19_1","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/psp4.12442","article-title":"Time\u2010to\u2010event modeling of peripheral neuropathy: platform analysis of eight valine\u2010citrulline\u2010monomethylauristatin E antibody\u2010drug conjugates","volume":"8","author":"K\u00e5gedal M.","year":"2019","journal-title":"CPT Pharmacometrics Syst. Pharmacol."},{"key":"e_1_2_11_20_1","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1002\/psp4.13049","article-title":"Case\u2010control matching\u2010guided exposure\u2010efficacy relationship for avelumab in patients with urothelial carcinoma","volume":"12","author":"Soltantabar P.","year":"2023","journal-title":"CPT Pharmacometrics Syst. Pharmacol."}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70466","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.70466","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70466","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:59:26Z","timestamp":1789012766000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.70466"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":20,"alternative-id":["10.1002\/cpt.70466"],"URL":"https:\/\/doi.org\/10.1002\/cpt.70466","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]},"assertion":[{"value":"2026-02-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cpt.70466"}}