{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T03:07:50Z","timestamp":1778728070259,"version":"3.51.4"},"reference-count":22,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"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":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Nemtabrutinib is a Bruton's tyrosine kinase (BTK) inhibitor under clinical investigation in patients with hematologic malignancies, including chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL\/SLL). Nemtabrutinib plasma concentration data from 578 patients enrolled in phase 1 and 2 clinical studies, treated with doses from 5 to 80\u2009mg daily were used to develop a preliminary population pharmacokinetic (PK) model. A two\u2010compartment model with first\u2010order absorption with time delay, and first\u2010order elimination described the data accurately. A full covariate modeling approach was adopted to evaluate prespecified clinically meaningful covariates. The final model included the impact of body weight, sex, race, and disease indication on clearance (CL) and central volume of distribution; age, albumin, moderate CYP3A4 inducers, strong CYP3A4 inhibitors, mild hepatic and moderate renal impairment on CL; and acid reducing agents (ARAs) (i.e., proton pump inhibitors, H2 antagonists, and antacids) on bioavailability. The effect of CYP3A4 modulators and ARAs was estimated to be very low (&lt;\u20094%) and none of the intrinsic factors were found to have a clinically significant impact on nemtabrutinib PK. Preliminary exposure\u2010efficacy analysis in patients with CLL\/SLL showed a significant trend of increased probability of best overall response with increased exposure to nemtabrutinib, while preliminary exposure\u2010safety in patients with hematologic malignancies showed a significant trend between increased exposure and increased probability of any\u2010grade drug\u2010related adverse events (as assessed by investigator) and any\u2010grade hypertension events. Taken together, these exposure\u2010response analyses suggest that 65\u2009mg daily is an appropriate dose for nemtabrutinib monotherapy treatment of patients with CLL\/SLL.<\/jats:p>","DOI":"10.1002\/psp4.70257","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T03:36:58Z","timestamp":1777693018000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetic Modeling and Exposure\u2010Response Analyses of Nemtabrutinib in Patients With Hematologic Malignancies"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8137-7712","authenticated-orcid":false,"given":"Chiara C.","family":"Kemal","sequence":"first","affiliation":[{"name":"Merck &amp; co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thijs J.","family":"Zweers","sequence":"additional","affiliation":[{"name":"Certara Inc., Department of Integrated Drug Development  Radnor Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6006-1567","authenticated-orcid":false,"given":"Elke H. J.","family":"Krekels","sequence":"additional","affiliation":[{"name":"Certara Inc., Department of Integrated Drug Development  Radnor Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2706-1342","authenticated-orcid":false,"given":"Manash S.","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Merck &amp; co., Inc.  Rahway New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2015.0045"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-018-0779-z"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12600"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31831"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13427"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.70.2282"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023023659"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024014206"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2114110"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-23-0670"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.16_suppl.TPS7593"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-163596"},{"key":"e_1_2_9_15_1","unstructured":"M. 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