{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T10:12:28Z","timestamp":1793873548366,"version":"4.6.1"},"reference-count":24,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"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":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Telisotuzumab vedotin (Teliso\u2010V; ABBV\u2010399) is an antibody\u2010drug conjugate (ADC) comprised of the c\u2010Met targeting antibody telisotuzumab (ABT\u2010700) conjugated to the potent cytotoxic monomethyl auristatin E (MMAE). Teliso\u2010V has been evaluated for treating solid tumors and is approved for adults with locally\u2010advanced or metastatic non\u2010squamous non\u2010small cell lung cancer with high c\u2010Met protein overexpression (\u226550% tumor cells with strong [+3] staining; determined by FDA\u2010approved test), who have received prior systemic therapy. Here, physiologically\u2010based pharmacokinetic (PBPK) modeling was utilized to evaluate Teliso\u2010V drug\u2010drug interaction (DDI) potential. A published PBPK\u2010model for MMAE as the primary metabolite and a newly\u2010developed telisotuzumab model from existing pre\u2010clinical and clinical trial data were used to create a novel Teliso\u2010V PBPK\u2010model. Unconjugated MMAE release was modeled with drug\u2010to\u2010antibody ratio\u2010specific deconjugation rates, with non\u2010specific and catabolic clearance added to capture half\u2010life and overall PK profile. The Teliso\u2010V model was calibrated and validated using observed clinical trial data, requiring dose\u2010normalized exposure %PEs \u226450%. CYP3A\u2010mediated DDI simulations demonstrated that when Teliso\u2010V was modeled as the victim, a 43% increase and 70% decrease in MMAE AUC were predicted with ketoconazole (strong CYP3A4\u2010inhibitor) and rifampin (strong CYP3A4\u2010inducer) coadministration, respectively. DDI magnitude was comparable to that observed between another approved ADC with the same MMAE payload (brentuximab vedotin) and ketoconazole and rifampin. The current PBPK simulations demonstrated a lack of perpetrator effect of Teliso\u2010V on midazolam, a sensitive CYP3A substrate. The current analysis provides important information on Teliso\u2010V DDI potential and further demonstrates the utility of PBPK models, particularly in oncology, where dedicated DDI studies are challenging.<\/jats:p>","DOI":"10.1002\/jcph.70108","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T13:49:54Z","timestamp":1758808194000},"page":"1732-1745","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Assessment of Telisotuzumab Vedotin Drug\u2013Drug Interaction Potential Using Physiologically\u2010Based Pharmacokinetic Modeling and Simulations"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9838-5874","authenticated-orcid":false,"given":"Md Mahbubul Huq","family":"Riad","sequence":"first","affiliation":[{"name":"Clinical Pharmacology AbbVie Inc. North Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4375-4021","authenticated-orcid":false,"given":"Priya","family":"Brunsdon","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Inc. North Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2945-0449","authenticated-orcid":false,"given":"Rajeev","family":"Menon","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Inc. North Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9954-3798","authenticated-orcid":false,"given":"Patrick","family":"Marroum","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Inc. North Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3711-8718","authenticated-orcid":false,"given":"Apurvasena","family":"Parikh","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Inc. North Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"EMRELIS (telisotuzumab vedotin) [package insert]","author":"AbbVie Inc"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.78.7697"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-0765"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1718"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-023-09877-5"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-014-0182-x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.116"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26195847"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12706"},{"key":"e_1_2_11_11_1","unstructured":"European Medicines Agency Committee for Medicinal Products for Human. Guideline on the reporting of physiologically based pharmacokinetic (PBPK) modelling and simulation. EMA\/CHMP\/458101\/2016. Accessed 11 December 2018.https:\/\/www.ema.europa.eu\/en\/reporting\u2010physiologically\u2010based\u2010pharmacokinetic\u2010pbpk\u2010modelling\u2010simulation\u2010scientific\u2010guideline."},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-19-0529"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-019-09639-2"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2155"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-014-9640-5"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2017.09.033"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.28965"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2010.497487"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2670"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00867-1"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12174"},{"key":"e_1_2_11_22_1","unstructured":"Astellas Pharma US.PADCEV (enfortumab vedotin) [package insert]. U.S. Food and Drug Administration. Revised February 2025.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/761137s029lbl.pdf"},{"key":"e_1_2_11_23_1","volume-title":"POLIVY (polatuzumab vedotin) [package insert]","author":"Genentech, Inc"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11113080"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-009-0716-z"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70108","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70108","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:07:15Z","timestamp":1772982435000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,25]]},"references-count":24,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/jcph.70108"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70108","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,25]]},"assertion":[{"value":"2025-06-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}