{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T14:01:58Z","timestamp":1776693718106,"version":"3.51.2"},"reference-count":21,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pemigatinib is a selective, potent, oral inhibitor of fibroblast growth factor receptor (FGFR)1\u20133 with efficacy in patients with previously treated, advanced\/metastatic cholangiocarcinoma (CCA) with <jats:italic>FGFR2<\/jats:italic> alterations. A previously developed population pharmacokinetic (PK) model of pemigatinib was refined using an updated dataset with 467 participants from seven clinical studies, including patients with CCA. Updated PK model parameters were used to evaluate the association between pemigatinib exposure and efficacy and safety. Pemigatinib PK was adequately described by a two\u2010compartment model with linear elimination and sequential zero\u2010 and first\u2010order absorption. The final model successfully minimized, had a successful covariance step, and showed unbiased goodness\u2010of\u2010fit. Estimated first\u2010order absorption rate constant and apparent clearance were 3.7\/h and 10.7\u2009L\/h, respectively. Sex, baseline body weight, and concomitant use of phosphate binders, proton pump inhibitors, or histamine\u20102 antagonists significantly impacted PK parameters; however, the impact of covariates on PK exposure was not clinically significant. Steady\u2010state pemigatinib exposure and mean change from baseline in serum phosphate concentration were associated with objective response rate in a bell\u2010shaped relationship and were significantly associated with increased hyperphosphatemia. Pemigatinib exposure was associated with treatment\u2010emergent adverse events, such as decreased appetite, nausea, and stomatitis, although the relationships were shallow. Overall, analyses indicate that 13.5\u2009mg pemigatinib once daily in 21\u2010day\u2009cycles (2\u2009weeks on, 1\u2009week off) offers a favorable benefit\u2013risk profile in patients with advanced\/metastatic or surgically unresectable CCA and is the optimal dose for clinical development.<\/jats:p>","DOI":"10.1002\/psp4.13064","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T07:02:10Z","timestamp":1700118130000},"page":"1784-1794","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Population pharmacokinetic and exposure\u2010response analyses of pemigatinib in patients with advanced solid tumors including cholangiocarcinoma"],"prefix":"10.1002","volume":"12","author":[{"given":"Xiaohua","family":"Gong","sequence":"first","affiliation":[{"name":"Incyte Research Institute  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayman","family":"Akil","sequence":"additional","affiliation":[{"name":"Certara Strategic Consulting  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre","family":"Ndi","sequence":"additional","affiliation":[{"name":"Certara Strategic Consulting  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Ji","sequence":"additional","affiliation":[{"name":"Allorion Therapeutics  Natick Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Incyte Research Institute  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Lovern","sequence":"additional","affiliation":[{"name":"Certara Strategic Consulting  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuejun","family":"Chen","sequence":"additional","affiliation":[{"name":"Incyte Research Institute  Wilmington Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00222-7"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.8"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2022.100641"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-10-695973"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.02.001"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30109-1"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2021-148103"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-163099"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2020.103091"},{"key":"e_1_2_11_11_1","unstructured":"PEMAZYRE\u00ae (pemigatinib).Full prescribing information Incyte Corporation Wilmington DE USA.2022."},{"key":"e_1_2_11_12_1","unstructured":"JiT LihouC AsatianiE et\u00a0al.Pharmacokinetics and pharmacodynamics of pemigatinib a potent and selective inhibitor of FGFR 1 2 and 3 in patients with advanced malignancies. AACR\u2010NCI\u2010EORTC symposium on molecular targets and cancer therapeutics; 2019 October 26\u201330; Boston MA."},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-021-03184-z"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14954"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1038"},{"key":"e_1_2_11_16_1","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2023"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.067694"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12805"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.21360"},{"key":"e_1_2_11_21_1","unstructured":"European Medicines Agency.Assessment report: Pemazyre. February 25 2021; 1\u2013136. 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