Population Pharmacokinetics of Encorafenib and Binimetinib in Real-World BRAFV600E/K-Mutant Metastatic Melanoma Patients in Comparison with Clinical Results

Population Pharmacokinetics of Encorafenib and Binimetinib in Real-World BRAFV600E/K-Mutant Metastatic Melanoma Patients in Comparison with Clinical Results | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 11 September 2025 V1 Latest version Share on Population Pharmacokinetics of Encorafenib and Binimetinib in Real-World BRAFV600E/K-Mutant Metastatic Melanoma Patients in Comparison with Clinical Results Authors : Yuan J. Pétermann , Alicja Puszkiel , Abbas Khani , Nora Kramkimel , Elisa Funck-Brentano , Benédicte Oules , Sarah Bouchereau , Michel Vidal , Xavier DECLEVES , Chantal Csajka , Benoit Blanchet , and Monia Guidi 0000-0002-6419-9317 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.175758519.96583383/v1 216 views 111 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Aim : Despite their recent approval, encorafenib and binimetinib pharmacokinetic (PK) studies in real-world cancer patients remain scarce. We aimed to characterize their population pharmacokinetics (popPK) in routine care clinical care and compare real-life exposure metrics with clinical trial data. Methods : We conducted population pharmacokinetic (popPK) analyses in real-life patients with BRAF V600E/K -mutant metastatic melanoma to characterize interindividual variability (IIV) and identify potential covariates susceptible to influence the drugs PK. These models allowed the comparison between patients PK metrics (i.e., trough concentration, C min , maximal concentration, C max , and area under the curve, AUC τ ) with data from clinical trials. Results : Encorafenib and binimetinib data were available from 66 and 69 patients, respectively, providing 310 and 311 plasma concentrations collected during routine therapeutic drug monitoring (TDM). For both drugs, a two-compartment model with first-order absorption and linear elimination best described the concentration–time data. Including IIV on clearance and intercompartmental clearance, and, for encorafenib, on the peripheral volume of distribution, significantly improved model performance. No clinically relevant covariate impacted the PK parameters. Model-predicted PK metrics (geometric mean and CV(%)) for encorafenib and binimetinib in our real-life population were: C min 19 ng/mL (73%) and 55 ng/mL (56%), C max 3378 ng/mL (30%) and 367 ng/mL (24%), and half-lives 12.5 h (95%) and 7.3 h (67%), respectively. Encorafenib AUC 24h was 15785 ng·h/mL (17%) and binimetinib AUC 12h was 2003 ng·h/mL (22%). Conclusion : Overall, these metrics are comparable to those reported in clinical trial data; yet the absence of robust PK/pharmacodynamic evidence continues to challenge optimal TDM. Supplementary Material File (20250903_binimetinib_encorafenib_poppk_bjcp.docx) Download 2.17 MB Information & Authors Information Version history V1 Version 1 11 September 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Yuan J. Pétermann Centre Hospitalier Universitaire Vaudois View all articles by this author Alicja Puszkiel Assistance Publique - Hopitaux de Paris View all articles by this author Abbas Khani Centre Hospitalier Universitaire Vaudois View all articles by this author Nora Kramkimel Assistance Publique - Hopitaux de Paris View all articles by this author Elisa Funck-Brentano Hopital Ambroise-Pare View all articles by this author Benédicte Oules Assistance Publique - Hopitaux de Paris View all articles by this author Sarah Bouchereau Hopital Ambroise-Pare View all articles by this author Michel Vidal Assistance Publique - Hopitaux de Paris View all articles by this author Xavier DECLEVES Assistance Publique - Hopitaux de Paris View all articles by this author Chantal Csajka Centre Hospitalier Universitaire Vaudois View all articles by this author Benoit Blanchet Assistance Publique - Hopitaux de Paris View all articles by this author Monia Guidi 0000-0002-6419-9317 [email protected] Centre Hospitalier Universitaire Vaudois View all articles by this author Metrics & Citations Metrics Article Usage 216 views 111 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Yuan J. Pétermann, Alicja Puszkiel, Abbas Khani, et al. Population Pharmacokinetics of Encorafenib and Binimetinib in Real-World BRAFV600E/K-Mutant Metastatic Melanoma Patients in Comparison with Clinical Results. Authorea . 11 September 2025. DOI: https://doi.org/10.22541/au.175758519.96583383/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); Cited by Hamza Sayadi, Yeleen Fromage, Marc Labriffe, Caroline Monchaud, Héloïse Jourdain, Hélène Géniaux, Jean-Baptiste Woillard, From empirical caution to precision resumption: model-informed management of a binimetinib overdose in a frail elderly patient, European Journal of Clinical Pharmacology, 82 , 4, (2026). https://doi.org/10.1007/s00228-026-04040-8 Crossref Loading... View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. 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