{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T16:11:48Z","timestamp":1779120708765,"version":"3.51.4"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Pharmacokinet"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1007\/s40262-025-01608-y","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T13:40:04Z","timestamp":1773322804000},"page":"693-707","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetic Modeling of Encorafenib in Healthy Participants and Patients with BRAF V600-Mutant Solid Tumors: A Semi-mechanistic Autoinduction Model"],"prefix":"10.1007","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3642-7757","authenticated-orcid":false,"given":"Derek Z.","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6061-1442","authenticated-orcid":false,"given":"Erik M.","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1174-966X","authenticated-orcid":false,"given":"Joseph","family":"Piscitelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2301-0538","authenticated-orcid":false,"given":"Yazdi K.","family":"Pithavala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6547-2186","authenticated-orcid":false,"given":"Jennifer E.","family":"Hibma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"1608_CR1","unstructured":"BRAFTOVI\u24c7 (encorafenib). Package insert. New York, NY, USA; Pfizer."},{"key":"1608_CR2","unstructured":"BRAFTOVI\u24c7 (encorafenib). Summary of product characteristics. New York, NY, USA; Pfizer."},{"key":"1608_CR3","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.1140","volume":"11","author":"L Wollenberg","year":"2023","unstructured":"Wollenberg L, Hahn E, Williams J, Litwiler K. A phase I, single-center, open-label study to investigate the absorption, distribution, metabolism and excretion of encorafenib following a single oral dose of 100\u2009mg [14 C] encorafenib in healthy male subjects. Pharmacol Res Perspect. 2023;11:e01140.","journal-title":"Pharmacol Res Perspect"},{"key":"1608_CR4","doi-asserted-by":"publisher","first-page":"5339","DOI":"10.1158\/1078-0432.CCR-16-2923","volume":"23","author":"JP Delord","year":"2017","unstructured":"Delord JP, Robert C, Nyakas M, McArthur GA, Kudchakar R, Mahipal A, et al. Phase I dose-escalation and -expansion study of the BRAF inhibitor encorafenib (LGX818) in metastatic BRAF-mutant melanoma. Clin Cancer Res. 2017;23:5339\u201348.","journal-title":"Clin Cancer Res"},{"key":"1608_CR5","unstructured":"US Food and Drug Administration. Encorafenib (BRAFTOVI(R)) US FDA multi-discipline review. 2018. www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2018\/210496Orig1s000MultidisciplineR.pdf."},{"key":"1608_CR6","doi-asserted-by":"publisher","first-page":"2589","DOI":"10.1021\/acs.molpharmaceut.3c00016","volume":"20","author":"J Piscitelli","year":"2023","unstructured":"Piscitelli J, Hens B, Tomaszewska I, Wollenberg L, Litwiler K, McAllister M, et al. Effect of food and a proton-pump inhibitor on the absorption of encorafenib: an in vivo-in vitro-in silico approach. Mol Pharm. 2023;20:2589\u201399.","journal-title":"Mol Pharm"},{"key":"1608_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2024.114073","volume":"204","author":"D Schadendorf","year":"2024","unstructured":"Schadendorf D, Dummer R, Flaherty KT, Robert C, Arance A, de Groot JWB, et al. COLUMBUS 7-year update: a randomized, open-label, phase III trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF V600E\/K-mutant melanoma. Eur J Cancer. 2024;204:114073.","journal-title":"Eur J Cancer"},{"key":"1608_CR8","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyae291","author":"D Tripathy","year":"2024","unstructured":"Tripathy D, Blum JL, Karuturi MS, McCune S, Kurian S, Moezi M, et al. Real-world effectiveness of palbociclib plus endocrine therapy in HR+\/HER2- advanced breast cancer: final results from the POLARIS trial. Oncologist. 2024. https:\/\/doi.org\/10.1093\/oncolo\/oyae291.","journal-title":"Oncologist"},{"issue":"15_suppl","key":"1608_CR9","doi-asserted-by":"publisher","first-page":"10022","DOI":"10.1200\/JCO.2020.38.15_suppl.10022","volume":"38","author":"R Dummer","year":"2020","unstructured":"Dummer R, Sandhu SK, Miller WH, Butler MO, Blank CU, Mu\u00f1oz-Couselo E, et al. A phase II, multicenter study of encorafenib\/binimetinib followed by a rational triple-combination after progression in patients with advanced BRAF V600-mutated melanoma (LOGIC2). J Clin Oncol. 2020;38(15_suppl):10022.","journal-title":"J Clin Oncol"},{"issue":"15_suppl","key":"1608_CR10","doi-asserted-by":"publisher","first-page":"3544","DOI":"10.1200\/JCO.2016.34.15_suppl.3544","volume":"34","author":"J Tabernero","year":"2016","unstructured":"Tabernero J, Geel RV, Guren TK, Yaeger RD, Spreafico A, Faris JE, et al. Phase 2 results: encorafenib (ENCO) and cetuximab (CETUX) with or without alpelisib (ALP) in patients with advanced BRAF mutant colorectal cancer (BRAFm CRC). J Clin Oncol. 2016;34(15_suppl):3544.","journal-title":"J Clin Oncol"},{"issue":"4","key":"1608_CR11","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1200\/JCO.20.02088","volume":"39","author":"J Tabernero","year":"2021","unstructured":"Tabernero J, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, et al. Encorafenib plus cetuximab as a new standard of care for previously treated BRAF V600E-mutant metastatic colorectal cancer: updated survival results and subgroup analyses from the BEACON study. J Clin Oncol. 2021;39(4):273\u201384.","journal-title":"J Clin Oncol"},{"issue":"7","key":"1608_CR12","doi-asserted-by":"publisher","first-page":"781","DOI":"10.2217\/fon-2021-1250","volume":"18","author":"GJ Riely","year":"2022","unstructured":"Riely GJ, Ahn MJ, Felip E, Ramalingam SS, Smit EF, Tsao AS, et al. Encorafenib plus binimetinib in patients with BRAF(V600)-mutant non-small cell lung cancer: phase II PHAROS study design. Future Oncol. 2022;18(7):781\u201391.","journal-title":"Future Oncol"},{"issue":"19","key":"1608_CR13","doi-asserted-by":"publisher","first-page":"5102","DOI":"10.1158\/1078-0432.CCR-19-3550","volume":"26","author":"RJ Sullivan","year":"2020","unstructured":"Sullivan RJ, Weber J, Patel S, Dummer R, Carlino MS, Tan DSW, et al. A phase Ib\/II study of the BRAF inhibitor encorafenib plus the MEK inhibitor binimetinib in patients with BRAF(V600E\/K)-mutant solid tumors. Clin Cancer Res. 2020;26(19):5102\u201312.","journal-title":"Clin Cancer Res"},{"key":"1608_CR14","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.1128\/AAC.05792-11","volume":"56","author":"W Smythe","year":"2012","unstructured":"Smythe W, Khandelwal A, Merle C, Rustomjee R, Gninafon M, Bocar Lo M, et al. A semimechanistic pharmacokinetic-enzyme turnover model for rifampin autoinduction in adult tuberculosis patients. Antimicrob Agents Chemother. 2012;56:2091\u20138.","journal-title":"Antimicrob Agents Chemother"},{"key":"1608_CR15","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1002\/cpt.778","volume":"103","author":"RJ Svensson","year":"2018","unstructured":"Svensson RJ, Aarnoutse RE, Diacon AH, Dawson R, Gillespie SH, Boeree MJ, et al. A population pharmacokinetic model incorporating saturable pharmacokinetics and autoinduction for high rifampicin doses. Clin Pharmacol Ther. 2018;103:674\u201383.","journal-title":"Clin Pharmacol Ther"},{"key":"1608_CR16","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1164\/rccm.201912-2489OC","volume":"202","author":"JE Hibma","year":"2020","unstructured":"Hibma JE, Radtke KK, Dorman SE, Jindani A, Dooley KE, Weiner M, et al. Rifapentine population pharmacokinetics and dosing recommendations for latent tuberculosis infection. Am J Respir Crit Care Med. 2020;202:866\u201377.","journal-title":"Am J Respir Crit Care Med"},{"key":"1608_CR17","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1208\/s12248-009-9133-0","volume":"11","author":"RM Savic","year":"2009","unstructured":"Savic RM, Karlsson MO. Importance of shrinkage in empirical bayes estimates for diagnostics: problems and solutions. AAPS J. 2009;11:558\u201369.","journal-title":"AAPS J"},{"issue":"2","key":"1608_CR18","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.131","volume":"3","author":"RJ Keizer","year":"2015","unstructured":"Keizer RJ, Jansen RS, Rosing H, Thijssen B, Beijnen JH, Schellens JH, et al. Incorporation of concentration data below the limit of quantification in population pharmacokinetic analyses. Pharmacol Res Perspect. 2015;3(2):e00131.","journal-title":"Pharmacol Res Perspect"},{"issue":"6","key":"1608_CR19","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1002\/psp4.70015","volume":"14","author":"M Wijk","year":"2025","unstructured":"Wijk M, Wasmann RE, Jacobson KR, Svensson EM, Denti P. A pragmatic approach to handling censored data below the lower limit of quantification in pharmacokinetic modeling. CPT Pharmacometrics Syst Pharmacol. 2025;14(6):1042\u20139.","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"key":"1608_CR20","doi-asserted-by":"publisher","first-page":"2675","DOI":"10.1111\/cts.13662","volume":"16","author":"E Hahn","year":"2023","unstructured":"Hahn E, Chavira R, Wollenberg L, Tan W, Reddy MB. Impact of posaconazole and diltiazem on pharmacokinetics of encorafenib, a BRAF V600 kinase inhibitor for melanoma and colorectal cancer with BRAF mutations. Clin Transl Sci. 2023;16:2675\u201386.","journal-title":"Clin Transl Sci"}],"container-title":["Clinical Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-025-01608-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40262-025-01608-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-025-01608-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T15:50:41Z","timestamp":1779119441000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40262-025-01608-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,12]]},"references-count":20,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["1608"],"URL":"https:\/\/doi.org\/10.1007\/s40262-025-01608-y","relation":{},"ISSN":["0312-5963","1179-1926"],"issn-type":[{"value":"0312-5963","type":"print"},{"value":"1179-1926","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,12]]},"assertion":[{"value":"22 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"D.Z.Y., E.M.H., J.P., Y.K.P., and J.E.H. are employees of Pfizer and hold Pfizer stock.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"These studies were conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. In addition, all local regulatory requirements were followed, particularly those afording greater protection to the safety of trial participants. An institutional review board approved the protocols, and all participants gave written informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"All participants provided written informed consent before undergoing any study procedures.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"Upon reasonable request and participant to review, Pfizer will provide the data that support the findings of this study. Participant to certain criteria, conditions, and exceptions, Pfizer may also provide access to the related individual de-identifi ed participant data from Pfizer-sponsored global interventional clinical studies conducted for medicines, vaccines, and medical devices (1) for indications that have been approved in the USA and\/or EU or (2) in programs that have been terminated (that is, development for all indications has been discontinued). Pfizer will also consider requests for the protocol, data dictionary, and statistical analysis plan. See\n                      \n                      for more information. Data may be requested from Pfizer trials 24 months after study completion. The de-identifi ed participant data will be made available, via a secure portal, to researchers whose proposals meet the research criteria and other conditions, and for which an exception does not apply. To gain access, data requestors must enter into a data access agreement with Pfizer.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data Availability"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code Availability"}},{"value":"D.Z.Y., E.M.H., J.P., Y.K.P., and J.E.H. designed and carried out the research, analyzed the data, and wrote themanuscript.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author Contributions"}}]}}