{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:20:32Z","timestamp":1793118032668,"version":"4.5.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":326,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Huntsman Cancer Institute\u2019s Cancer Center Support","award":["P30CA42014"],"award-info":[{"award-number":["P30CA42014"]}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019697","name":"Plexxikon","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019697","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022274","name":"Daiichi Sankyo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glioblastoma (GBM) has a median survival of &amp;lt;2 years. Pexidartinib (PLX3397) is a small-molecule inhibitor of CSF1R, KIT, and oncogenic FTL3, which are implicated in GBM treatment resistance. Results from glioma models indicate that combining radiation therapy (RT) and pexidartinib reduces radiation resistance. We added pexidartinib to standard-of-care RT\/temozolomide (TMZ) in patients with newly diagnosed GBM to assess the therapeutic benefit of altering the tumor microenvironment with pexidartinib.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this open-label, dose-escalation, multicenter, Phase 1b\/2 trial, pexidartinib was administered in combination with RT\/TMZ followed by adjuvant pexidartinib\u2005+\u2005TMZ. During Phase 1b, pexidartinib was given 5 or 7 days\/week at multiple dosing levels. The primary Phase 1b endpoint was the recommended Phase 2 dose (RP2D). Phase 2 patients received the RP2D with the primary endpoint of median progression-free survival (mPFS). Secondary objectives were median overall survival (mOS), pharmacokinetics, and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The RP2D of pexidartinib was 800\u00a0mg\/day for 5 days\/week during RT\/TMZ, followed by 800\u00a0mg\/day for 7 days\/week with adjuvant TMZ. mPFS was 6.7 months (90% CI: 4.5, 11.5) for the modified intention-to-treat population. The actual mOS was 13.1 months (90% CI: 11.5, 24.5), and the mOS corrected for comparison with matched historical controls was 18.8 months (95% CI: 12.6, 28.0).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This trial established the RP2D of pexidartinib in combination with RT\/TMZ and adjuvant TMZ. Pexidartinib was generally safe and well tolerated. Although the study regimen with pexidartinib was not efficacious, pharmacodynamic studies showed modulation of systemic markers that could lead to alteration of the tumor microenvironment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/noajnl\/vdae202","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T23:25:57Z","timestamp":1732058757000},"source":"Crossref","is-referenced-by-count":10,"title":["Phase 1b\/2 study of orally administered pexidartinib in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9138-8658","authenticated-orcid":false,"given":"Joe S","family":"Mendez","sequence":"first","affiliation":[{"name":"Huntsman Cancer Institute , Salt Lake City, UT ,","place":["USA"]},{"name":"Department of Neurosurgery, University of Utah , Salt Lake City, UT 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