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We aimed to characterize their population pharmacokinetics (popPK) in routine clinical care and compare real-life exposure metrics with clinical trials data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted population pharmacokinetic (popPK) analyses in real-world patients with BRAF\n                      <jats:sup>V600E\/K<\/jats:sup>\n                      -mutant metastatic melanoma to characterize interindividual variability (IIV) and identify significant covariates in MonolixSuite\u2122. Final model-based Bayesian individual PK metrics (i.e., trough concentration, C\n                      <jats:sub>min<\/jats:sub>\n                      , maximal concentration, C\n                      <jats:sub>max<\/jats:sub>\n                      , unbound average concentration, C\n                      <jats:sub>average<\/jats:sub>\n                      , and area under the curve, AUC\n                      <jats:sub>\u03c4<\/jats:sub>\n                      ) were compared with data from clinical trials and potency-anchored metrics (reported half-maximal inhibitory concentration, IC\n                      <jats:sub>50<\/jats:sub>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Data from 66 encorafenib and 69 binimetinib patients (310 and 311 samples) were analyzed. For both drugs, a two-compartment model with first-order absorption and linear elimination best described the data. None of the studied covariates were significantly associated with model parameters. Model-predicted PK metrics (geometric mean and CV(%)) for encorafenib and binimetinib at 450\u00a0mg QD and 45\u00a0mg BID were: C\n                      <jats:sub>min<\/jats:sub>\n                      19 ng\/mL (73%) and 55 ng\/mL (56%), C\n                      <jats:sub>max<\/jats:sub>\n                      3378 ng\/mL (30%) and 367 ng\/mL (24%), and half-lives 12.5\u00a0h (95%) and 7.3\u00a0h (67%), respectively. Encorafenib AUC\n                      <jats:sub>24h<\/jats:sub>\n                      was 15,785 ng\u00b7h\/mL (17%) and binimetinib AUC\n                      <jats:sub>12h<\/jats:sub>\n                      was 2003 ng\u00b7h\/mL (22%). Monte Carlo simulation showed that reducing encorafenib from 450\u00a0mg to 300\u00a0mg once daily lowered unbound C\n                      <jats:sub>average<\/jats:sub>\n                      by 33% while maintaining substantial coverage relative to IC\n                      <jats:sub>50<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, these metrics are comparable to those reported in clinical trial data. This population PK model could be useful to explore the exposure-response relationship in future PK\/PD studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00280-026-04876-y","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T04:54:32Z","timestamp":1773723272000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population pharmacokinetics of encorafenib and binimetinib in real-world patients with BRAFV600E\/K-mutant metastatic melanoma"],"prefix":"10.1007","volume":"96","author":[{"given":"Yuan J.","family":"P\u00e9termann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Puszkiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbas","family":"Khani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Kramkimel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Funck-Brentano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben\u00e9dicte","family":"Oules","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Bouchereau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Vidal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Decleves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Csajka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Blanchet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monia","family":"Guidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"issue":"12","key":"4876_CR1","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1007\/s40265-018-0963-x","volume":"78","author":"M Shirley","year":"2018","unstructured":"Shirley M (2018) Encorafenib and binimetinib: first global approvals. 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BB has received consulting and speaking fees, travel grants (Bristol Myers Squibb, EISAI, Glaxo Smith Kline, Pierre Fabre Oncology and Pfizer). Additionally, EB has received compensation from Bristol Myers Squibb, MSD, Novartis, Pierre Fabre, and Sun Pharma.Previous versions of the model of encorafenib and binimetinib were presented at the PAGE meeting 2024.The other coauthors have no conflict of interests to declare.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"29"}}