{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:27:22Z","timestamp":1791358042927,"version":"4.3.1"},"reference-count":31,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007886","name":"Dana-Farber Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007886","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001445","name":"Alex's Lemonade Stand Foundation for Childhood Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001445","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fimepinostat, an oral dual inhibitor of histone deacetylase (HDAC) and phosphatidylinositol\u20104,5\u2010bisphosphate 3\u2010kinase (PI3K), has shown activity in preclinical models of Myc\u2010driven pediatric malignancies. This Phase 1 trial aimed to determine the recommended pediatric Phase 2 dose (RPP2D), describe the toxicity profile, and evaluate the pharmacokinetics of fimepinostat in children with relapsed and refractory solid and central nervous system (CNS) tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This multicenter, Phase 1 study enrolled patients ages 1\u201321\u2009years with relapsed or refractory solid tumors, CNS tumors, or lymphoma. The dose\u2010escalation phase followed a 3\u2009+\u20093 design, starting at 27.5\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      and escalating to 45\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      . Following dose escalation, three expansion cohorts were opened including cohorts for patients with Myc(n)\u2010driven neuroblastoma, Myc\u2010driven extracranial solid tumors, and diffuse large B\u2010cell lymphoma or Burkitt lymphoma. The pharmacokinetics of fimepinostat and its metabolites were studied after the first dose.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010six patients were enrolled, with 25 receiving treatment. The median age was 13.6\u2009years (range: 4.1\u201320.9). In the dose\u2010escalation phase, 12 patients were evaluable for DLT assessment. The RPP2D was initially determined to be 45\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      but was revised to 35\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      after observing DLTs in the dose\u2010expansion phase. Treatment\u2010related adverse events were primarily hematologic and gastrointestinal. No objective responses were observed in 23 evaluable patients. Three patients had stable disease for over four cycles, including a patient with\n                      <jats:italic>MYCN<\/jats:italic>\n                      amplified neuroblastoma with stable disease for 24\u2009cycles. Pharmacokinetic analysis showed significant interpatient variability and rapid conversion of fimepinostat to its metabolites.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Fimepinostat was tolerable at a dose of 35\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      in children with relapsed and refractory solid and CNS tumors, but lacked significant clinical activity. Discovery of drugs to target Myc continues to be a high priority for childhood cancers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov identifier: NCT02909777<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71417","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T17:50:06Z","timestamp":1764265806000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Phase 1 Trial of Fimepinostat in Children and Adolescents With Relapsed and Refractory Solid and\n                    <scp>CNS<\/scp>\n                    Tumors"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5994-2604","authenticated-orcid":false,"given":"David 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