{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:15:36Z","timestamp":1793042136749,"version":"4.5.0"},"reference-count":32,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"10","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Neurofibromatosis type 1 (NF1)\u2013associated plexiform neurofibroma (PN) can substantially affect quality of life. The capsule and granule formulations of selumetinib (ARRY-142886, AZD6244) are approved for pediatric patients with symptomatic, inoperable NF1-PN (age \u22651 to 3 years, region dependent). SPRINKLE (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT05309668\">NCT05309668<\/jats:ext-link>\n                      ) assessed pharmacokinetics (PK), safety, and palatability of the selumetinib granule formulation in children (age \u22651 to &lt;7 years) with symptomatic, inoperable NF1-PN.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Participants enrolled into Global Cohort (GC)1 (\u22654 to &lt;7 years), GC2 (\u22651 to &lt;4 years), or the Japan Cohort (JC; \u22651 to &lt;7 years) received selumetinib 25 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      (dose equivalent) twice a day in 28-day cycles. Primary objectives assessed single-dose selumetinib PK exposure (area under concentration-time curve from time 0-12 hours [AUC\n                      <jats:sub>0-12<\/jats:sub>\n                      ]) in GCs and selumetinib safety. Secondary objectives assessed selumetinib and N-desmethyl selumetinib metabolite PK (single\/multiple dose), and palatability. At first data cutoff (April 8, 2024), all participants had completed \u22653 cycles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      There were 36 participants (GC1: n = 15, GC2: n = 17, JC: n = 4). Geometric mean (95% CI) selumetinib AUC\n                      <jats:sub>0-12<\/jats:sub>\n                      (single dose) in GC1 (n = 13) and GC2 (n = 15) was 1,902 (1,647 to 2,197) and 1,699 (1,436 to 2,009) h \u00d7 ng\/mL, respectively. Primary PK end point was met: 95% CIs of AUC\n                      <jats:sub>0-12<\/jats:sub>\n                      (single dose) were within the acceptance range on the basis of the capsule formulation exposure. Median duration of exposure was approximately 11 months (range, 2.7-25.3). 97.2% of participants had \u22651 treatment-related adverse event; most were grade 1 or 2 and none led to discontinuation or dose reduction. Most participants reported swallowing the medication without problems.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Selumetinib granule formulation (25 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      dose equivalent, twice a day) had comparable exposure to selumetinib capsule formulation, and was palatable with a manageable safety profile. Selumetinib granule formulation is potentially suitable for young children with NF1-PN who cannot swallow capsules.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-01447","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T21:00:08Z","timestamp":1769547608000},"page":"849-860","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetics and Safety of Selumetinib Granule Formulation in Children With Symptomatic, Inoperable Neurofibromatosis Type 1-Related Plexiform Neurofibromas (SPRINKLE; phase I\/II)"],"prefix":"10.1200","volume":"44","clinical-trial-number":[{"clinical-trial-number":"nct05309668","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3135-3872","authenticated-orcid":true,"given":"Pablo","family":"Hern\u00e1iz Driever","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology\/Hematology, Charit\u00e9 Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6375-2320","authenticated-orcid":true,"given":"Uwe R.","family":"Kordes","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7973-3300","authenticated-orcid":true,"given":"Ines B.","family":"Brecht","sequence":"additional","affiliation":[{"name":"Pediatric Hematology and Oncology, Children's Hospital, Eberhard-Karls-Universitaet Tuebingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4830-6204","authenticated-orcid":true,"given":"Veronica","family":"Saletti","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3408-3839","authenticated-orcid":true,"given":"Michael J.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Division of Oncology, The Children's Hospital of Philadelphia and the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail","family":"Doughton","sequence":"additional","affiliation":[{"name":"R&amp;D Clinical Development, Alexion, AstraZeneca Rare Disease, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Million","family":"Arefayene","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Safety Sciences, Alexion, AstraZeneca Rare Disease, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rigazio","sequence":"additional","affiliation":[{"name":"Quantitative Science, Alexion, AstraZeneca Rare Disease, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Lluch","sequence":"additional","affiliation":[{"name":"R&amp;D Clinical Development, Alexion, AstraZeneca Rare Disease, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nereida","family":"Llorente","sequence":"additional","affiliation":[{"name":"Global Patient Safety, Alexion, AstraZeneca Rare Disease, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5422-549X","authenticated-orcid":true,"given":"Scott J.","family":"Diede","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc, Rahway, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5984-6882","authenticated-orcid":true,"given":"Hector","family":"Salvador","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Hematology, Sant Joan de D\u00e9u Barcelona Hospital, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_12_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70063-8"},{"key":"e_1_3_12_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nov200"},{"key":"e_1_3_12_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.045906"},{"key":"e_1_3_12_5_2","volume-title":"GeneReviews","author":"Friedman JM","year":"1993","unstructured":"Friedman JM. 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