{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:52:12Z","timestamp":1792173132825,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cabozantinib is a small\u2010molecule tyrosine kinase inhibitor approved for the treatment of various locally advanced or metastatic solid tumors. The phase 1b COSMIC\u2010021 study evaluated cabozantinib as a monotherapy or in combination with atezolizumab in patients with advanced solid tumors, including castration\u2010resistant prostate cancer (CRPC). Relative to previous studies, the current analysis was conceived to improve the estimation of population pharmacokinetic (PopPK) parameters, including covariate effects, given the increased number of patients by including COSMIC\u2010021 data, and to support exposure\u2010response analyses in CRPC. A nonlinear mixed effects modeling approach was utilized and included evaluation of covariates, including demographics, laboratory values, hepatic function, tumor type, and combination treatment with atezolizumab. The PopPK analyses included 7513 cabozantinib PK samples from 2757 patients and healthy volunteers across 8 studies, including 2164 samples from 819 patients in COSMIC\u2010021. Cabozantinib PK was described by a 2\u2010compartment model with linear elimination and dual\u2010phase absorption. Apparent clearance of cabozantinib (CL\/F) was 2.06\u2009L\/h, and apparent central volume of distribution was 103\u2009L. Elimination half\u2010life was 104\u2009h. Combination treatment with atezolizumab did not impact cabozantinib PK. Sex and body weight had a minor impact on cabozantinib exposures. There was no significant impact of other covariates on cabozantinib PK. In conclusion, the 2\u2010compartment model with dual\u2010phase absorption described cabozantinib PK well, and the parameter estimates and identified covariates were consistent with previous analyses. The impact of covariates, including sex and body weight, on cabozantinib plasma exposures was not clinically relevant to warrant dosage adjustments.<\/jats:p>","DOI":"10.1111\/cts.70738","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:26:12Z","timestamp":1791519972000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetics of Cabozantinib: Updated Analyses Including Data in Combination With Atezolizumab in Patients With Castration\u2010Resistant Prostate Cancer and Other Tumor Types"],"prefix":"10.1111","volume":"19","author":[{"given":"Jason H.","family":"Williams","sequence":"first","affiliation":[{"name":"Exelixis, Inc.  Alameda California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanbin","family":"Li","sequence":"additional","affiliation":[{"name":"QuanTx Consulting  Mountain View California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4937-2775","authenticated-orcid":false,"given":"Ahmed A.","family":"Othman","sequence":"additional","affiliation":[{"name":"Exelixis, Inc.  Alameda California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-11-0264"},{"key":"e_1_2_13_3_1","unstructured":"Exelixis Inc \u201cCabometyx (Cabozantinib). Full Prescribing Information 2025\u201d."},{"key":"e_1_2_13_4_1","unstructured":"Genentech \u201cTECENTRIQ (atezolizumab). Full Prescribing Information 2016\u201d."},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2021-1096"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(22)00278-9"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-018-3581-0"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-023-01210-0"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0295-x"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1467"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-022-04500-9"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-024-01379-y"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00332-6"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2026982"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.00939"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.102376"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtocrr.2024.100666"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO-24-01675"},{"key":"e_1_2_13_19_1","unstructured":"ClinicalTrials.gov \u201cA phase 1b dose\u2010escalation study of cabozantinib (XL184) administered alone or in combination with atezolizumab to subjects with locally advanced or metastatic solid tumors \u201dhttps:\/\/clinicaltrials.gov\/study\/NCT03170960."},{"key":"e_1_2_13_20_1","unstructured":"US Food and Drug Administration \u201cPopulation Pharmacokinetics Guidance for Industry\u201d."},{"key":"e_1_2_13_21_1","unstructured":"European Medicines Agency \u201cCommittee for medicinal products for human use (CHMP) \u201dhttps:\/\/www.ema.europa.eu\/en\/committees\/committee\u2010medicinal\u2010products\u2010human\u2010use\u2010chmp."},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01061469"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-009-9133-0"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2020.102062"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2010.08.006"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.714"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70738","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.70738","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70738","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:17:52Z","timestamp":1792171072000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70738"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":25,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/cts.70738"],"URL":"https:\/\/doi.org\/10.1111\/cts.70738","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-08-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70738"}}