{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:19:07Z","timestamp":1788373147603,"version":"build-2803163510"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Ziftomenib, a potent, selective inhibitor that binds menin at the lysine methyltransferase 2 interaction site, has demonstrated promising clinical activity with manageable toxicity in heavily pretreated patients with acute myeloid leukemia (AML) and <jats:italic>nucleophosmin 1<\/jats:italic> mutations. This phase 1, open\u2010label study characterized the absorption, metabolism, excretion, and bioavailability of ziftomenib in healthy men and comprised two parts. In part A, a single oral dose of ziftomenib 400\u2009mg (containing 250\u2009\u03bcCi [<jats:sup>14<\/jats:sup>C]\u2010ziftomenib) was given to evaluate routes and rates of elimination, total radioactivity, and other pharmacokinetic parameters. In part B, a single oral dose of ziftomenib 400\u2009mg followed by an intravenous dose of ziftomenib &lt;\u2009100\u2009\u03bcg (containing 1\u2009\u03bcCi [<jats:sup>14<\/jats:sup>C]\u2010ziftomenib) was administered to evaluate absolute bioavailability (both <jats:italic>n<\/jats:italic>\u2009=\u20098 patients). A median t<jats:sub>max<\/jats:sub> of 3.5\u2009h and an elimination t<jats:sub>1\/2<\/jats:sub> of 61.5\u2009h demonstrated rapid ziftomenib absorption and enabled once\u2010daily dosing. Total radioactivity recovery was 89.7% in feces and 0.5% in urine over 480\u2009h. Absolute bioavailability of 12.9% was observed. Ziftomenib was primarily metabolized by oxidation, <jats:italic>N<\/jats:italic>\u2010demethylation, and <jats:italic>N<\/jats:italic>\u2010dealkylation, with 19 metabolites recovered in plasma. All metabolites were considered minor (&lt;\u200910% of total drug\u2010related exposure). Ziftomenib was the most abundant plasma component (&gt;\u200910% of total drug\u2010related exposure). In conclusion, ziftomenib underwent limited metabolism following absorption and was primarily excreted as unchanged parent drug in feces. Ziftomenib was well tolerated with no new safety concerns in healthy men. Considering the pharmacokinetic profile and manageable safety outcomes, these findings support further clinical investigation of ziftomenib as treatment for AML.<\/jats:p>","DOI":"10.1111\/cts.70153","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:56:33Z","timestamp":1739235393000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Pharmacokinetics and <scp>ADME<\/scp> Characterization After Oral and Intravenous Administration of [<scp><sup>14<\/sup>C<\/scp>]\u2010Ziftomenib in Healthy Male Participants"],"prefix":"10.1111","volume":"18","author":[{"given":"Amitava","family":"Mitra","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Kura Oncology, Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie Mackey","family":"Ahsan","sequence":"additional","affiliation":[{"name":"Clinical Development Kura Oncology, Inc.  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