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This drug\u2013drug interaction study assessed the effect of multiple\u2010dose administration of mobocertinib on the pharmacokinetics (PK) of midazolam, a sensitive cytochrome P450 3A substrate. Patients with locally advanced or metastatic non\u2010small cell lung cancer refractory\/intolerant to standard available therapy were enrolled. In Cycle 1 (Part A; PK cycle), a single 3\u2010mg oral dose of midazolam was administered on Days 1 and 24, and a single 1\u2010mg intravenous dose of midazolam was administered on Days 2 and 25. Mobocertinib 160\u00a0mg once daily was administered orally on Days 3\u201030. After Cycle 1, patients could continue receiving mobocertinib in 28\u2010day cycles in Part B of the study. The study objective was to characterize the effect of mobocertinib on the single oral\u2010 and intravenous\u2010dose PK of midazolam. Safety and exploratory efficacy were also assessed. Twenty\u2010six patients were enrolled, and 13 patients were PK\u2010evaluable. Safety findings were consistent with the known safety profile of mobocertinib, and diarrhea was the only Grade 3 or higher treatment\u2010related adverse event observed in more than 2 patients. Two of 16 patients with <jats:italic>EGFR<\/jats:italic> exon 20 insertion mutations were confirmed responders per investigator. Coadministration of mobocertinib decreased the area under the plasma concentration\u2013time curve from time zero to infinity of oral and intravenous midazolam by approximately 32% and 16%, respectively (geometric least\u2010squares mean ratios of 0.676 and 0.837, respectively).<\/jats:p>","DOI":"10.1002\/cpdd.1500","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T05:45:45Z","timestamp":1737006345000},"page":"252-262","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Drug\u2013Drug Interaction Study of Mobocertinib and Midazolam, a Cytochrome P450 3A Substrate, in Patients With Advanced Non\u2013Small Cell Lung Cancer"],"prefix":"10.1002","volume":"14","author":[{"given":"Michael J.","family":"Hanley","sequence":"first","affiliation":[{"name":"Takeda Development Center Americas, Inc.  Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Zhang","sequence":"additional","affiliation":[{"name":"Takeda Development Center Americas, Inc.  Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nick","family":"Pavlakis","sequence":"additional","affiliation":[{"name":"Royal North Shore Hospital,\u00a0 University of Sydney  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ross A.","family":"Soo","sequence":"additional","affiliation":[{"name":"National University Cancer Institute  Singapore Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthonie J.","family":"van der Wekken","sequence":"additional","affiliation":[{"name":"University of Groningen and University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinod","family":"Ganju","sequence":"additional","affiliation":[{"name":"Peninsula and Southeast Oncology  Frankston Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adela","family":"Pi\u00f1a","sequence":"additional","affiliation":[{"name":"Takeda Development Center Americas, Inc.  Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Dong","sequence":"additional","affiliation":[{"name":"Takeda Development Center Americas, Inc.  Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neeraj","family":"Gupta","sequence":"additional","affiliation":[{"name":"Takeda Development Center Americas, Inc.  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