{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:30:54Z","timestamp":1786689054984,"version":"build-2736575974"},"reference-count":14,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"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>Cofetuzumab pelidotin (Cofe\u2010P) is an anti\u2010protein tyrosine kinase 7 (PTK7) antibody\u2010drug conjugate (ADC) being investigated for the treatment of adults with PTK7\u2010expressing, recurrent non\u2010small cell lung cancer (NSCLC). The first\u2010in\u2010human (FIH) trial demonstrated tolerability of dosages \u2264\u20092.8\u2009mg\/kg once every 3\u2009weeks (Q3W) and \u2264\u20093.2\u2009mg\/kg Q2W. Population pharmacokinetics (popPK) and exposure\u2010response analyses were conducted to characterize Cofe\u2010P and unconjugated auristatin (Aur0101) payload pharmacokinetics and exposure\u2010efficacy (objective response rate (ORR)) and exposure\u2010safety (Grade \u2265\u20093 neutropenia, Grade \u2265\u20092 peripheral neuropathy or rash) endpoints to inform the selection of dosages for optimization. Data from the FIH (0.2\u20133.7\u2009mg\/kg Q3W, 2.1\u20133.2\u2009mg\/kg Q2W) and Phase 1b (2.8\u2009mg\/kg Q3W) studies were used for popPK and exposure\u2010response analyses. PopPK models adequately described pharmacokinetic data. Exposure\u2010response analyses showed that higher Cofe\u2010P (ADC) exposures increased the probability of achieving an objective response but also the occurrence of examined adverse events, particularly Grade \u2265\u20093 neutropenia. In non\u2010squamous epidermal growth factor receptor wild\u2010type NSCLC patients (\u2265\u200990% with PTK7 2+ staining), analyses predicted that 3.2\u2009mg\/kg vs. 2.8\u2009mg\/kg Q3W dosing led to a higher ORR (35% vs. 21%) while maintaining a manageable safety profile (Grade \u2265\u20093 neutropenia: \u2264\u200939%). Predicted ORR and Grade \u2265\u20093 neutropenia are improvements over the standard\u2010of\u2010care, docetaxel. Dosing regimens &lt;\u20092.4\u2009mg\/kg were not predicted to improve efficacy. Mean relative dose intensity was \u2265\u200986% across all Cofe\u2010P doses and schedules tested. Together, popPK and exposure\u2010response analyses support optimal dosing regimens of 2.4, 2.8, and 3.2\u2009mg\/kg Cofe\u2010P Q3W in patients with NSCLC.<\/jats:p>","DOI":"10.1002\/cpt.70432","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:03:10Z","timestamp":1786687390000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetics and Exposure\u2010Response Analyses to Support Cofetuzumab Pelidotin (\n                    <scp>ABBV<\/scp>\n                    \u2010647) Dose Optimization in Non\u2010Small Cell Lung Cancer Patients"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6879-6557","authenticated-orcid":false,"given":"Carla","family":"Biesdorf","sequence":"first","affiliation":[{"name":"AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3393-3723","authenticated-orcid":false,"given":"Melanie","family":"Rinas","sequence":"additional","affiliation":[{"name":"AbbVie Deutschland GmbH &amp; Co. KG  Ludwigshafen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0884-9976","authenticated-orcid":false,"given":"Benjamin","family":"Engelhardt","sequence":"additional","affiliation":[{"name":"AbbVie Deutschland GmbH &amp; Co. KG  Ludwigshafen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabih","family":"Saab","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6850-1045","authenticated-orcid":false,"given":"Cen","family":"Guo","sequence":"additional","affiliation":[{"name":"Pfizer Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3886-9134","authenticated-orcid":false,"given":"Cristiano","family":"Ferlini","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7142-2444","authenticated-orcid":false,"given":"Kevin J.","family":"Freise","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2945-0449","authenticated-orcid":false,"given":"Rajeev M.","family":"Menon","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5938-6062","authenticated-orcid":false,"given":"Akshanth R.","family":"Polepally","sequence":"additional","affiliation":[{"name":"AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.tcb.2006.07.003","article-title":"Emerging roles of pseudokinases","volume":"16","author":"Boudeau J.","year":"2006","journal-title":"Trends Cell Biol."},{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aag2611","article-title":"A PTK7\u2010targeted antibody\u2010drug conjugate reduces tumor\u2010initiating cells and induces sustained tumor regressions","volume":"9","author":"Damelin M.","year":"2017","journal-title":"Sci. Transl. 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Oncol."},{"key":"e_1_2_11_11_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.lungcan.2025.108492","article-title":"A phase 1b study of cofetuzumab pelidotin monotherapy in patients with PTK7\u2010expressing recurrent non\u2010small cell lung cancer","volume":"202","author":"Cho B.C.","year":"2025","journal-title":"Lung Cancer"},{"key":"e_1_2_11_12_1","volume-title":"Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases: Guidance for Industry","author":"U.S. Department of Health and Human Services, Food and Drug Administration, Oncology Center of Excellence, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER)","year":"2024"},{"key":"e_1_2_11_13_1","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2019.1699768","article-title":"Clinical pharmacology of vc\u2010MMAE antibody\u2010drug conjugates in cancer patients: learning from eight first\u2010in\u2010human phase 1 studies","volume":"12","author":"Li C.","year":"2020","journal-title":"MAbs"},{"key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2165\/00002512-200017010-00004","article-title":"Docetaxel: a review of its use in non\u2010small cell lung cancer","volume":"17","author":"Comer A.M.","year":"2000","journal-title":"Drugs Aging"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70432","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.70432","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70432","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:03:12Z","timestamp":1786687392000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.70432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":14,"alternative-id":["10.1002\/cpt.70432"],"URL":"https:\/\/doi.org\/10.1002\/cpt.70432","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]},"assertion":[{"value":"2026-04-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cpt.70432"}}