{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:10:49Z","timestamp":1770898249855,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"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":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:p>\n                    A clinical drug\u2013drug interaction (DDI) study was designed to evaluate the effect of single and multiple oral doses of encorafenib on the single oral dose pharmacokinetics (PK) of the cytochrome P450 (CYP) enzyme probe substrates, losartan (CYP2C9), midazolam (CYP3A4), caffeine (CYP1A2), omeprazole (CYP2C19), and dextromethorphan (CYP2D6) administered as a cocktail (Inje). This study was conducted, post\u2010approval, in patients with BRAF V600\u2010mutant advanced solid tumors, and aimed to address the remaining uncertainty in the DDI potential of encorafenib as a perpetrator of these CYP enzymes. Study participants received the cocktail on Days \u22127, 1, and 14 and continuous doses of encorafenib (450\u2009mg q.d.) and binimetinib (45\u2009mg b.i.d.) starting on Day 1. PK sampling and urine collection were conducted from 0 to 8\u2009hours on cocktail administration days. PK parameters were calculated for each participant using noncompartmental analysis of concentration\u2013time data or amount excreted for urine parameters. At steady\u2010state encorafenib plasma concentrations, midazolam plasma\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>last<\/jats:sub>\n                    decreased by 74% and 82%, respectively. No clinically significant DDIs were observed at encorafenib steady\u2010state concentrations with the other probe substrates of interest. The results from this clinical study indicate that encorafenib is a strong inducer of CYP3A (\u2265\u200980% decrease in midazolam area under the curve (AUC)) at steady state. Based on these results regarding co\u2010administration with encorafenib, sensitive substrates of CYP3A should be avoided or dose adjusted based on the recommendations of their approved product labeling. This information has been included in the updated prescribing information for encorafenib.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70117","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T07:02:24Z","timestamp":1762844544000},"page":"375-380","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Evaluation of the Drug Interaction Potential of Encorafenib in Combination With Binimetinib Using the Inje Cocktail in Patients With Cancer"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1174-966X","authenticated-orcid":false,"given":"Joseph","family":"Piscitelli","sequence":"first","affiliation":[{"name":"Pfizer Inc  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2721-3714","authenticated-orcid":false,"given":"Micaela B.","family":"Reddy","sequence":"additional","affiliation":[{"name":"Pfizer Inc  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4791-8655","authenticated-orcid":false,"given":"Lance","family":"Wollenberg","sequence":"additional","affiliation":[{"name":"Pfizer Inc  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8957-8826","authenticated-orcid":false,"given":"Laurence","family":"Del Frari","sequence":"additional","affiliation":[{"name":"Pierre Fabre Medicament  Toulouse France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Gong","sequence":"additional","affiliation":[{"name":"Pfizer Inc  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2043-851X","authenticated-orcid":false,"given":"Kyle","family":"Matschke","sequence":"additional","affiliation":[{"name":"Pfizer Inc  Collegeville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5657-4626","authenticated-orcid":false,"given":"Jason H.","family":"Williams","sequence":"additional","affiliation":[{"name":"Exelixis, Inc  King of Prussia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"e_1_2_11_1_1","unstructured":"BRAFTOVI (encorafenib) capsules prescribing information<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/210496s013lbl.pdf>."},{"key":"e_1_2_11_2_1","unstructured":"US Food and Drug Administration.Braftovi: multidisciplinary review<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2018\/210496Orig1s000MultidisciplineR.pdf> (2018)."},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-024-01352-9"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2923"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.41.1660"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13097"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.660"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-014-1716-8"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100187"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.3c00016"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199936060-00004"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2003.07.001"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-024-04676-2"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-3550"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02632-12"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-022-03304-3"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2022.105194"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2014.83"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.1140"},{"key":"e_1_2_11_20_1","volume-title":"Clinical Drug Interaction Studies \u2014 Cytochrome P450 Enzyme\u2010 and Transporter\u2010Mediated Drug Interactions Guidance for Industry","author":"US Food and Drug Administration"},{"key":"e_1_2_11_21_1","unstructured":"European Medicines Agency.ICH Guideline M12. 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