{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T16:05:12Z","timestamp":1792253112026,"version":"4.4.0"},"reference-count":20,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"7","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2021,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Patients with neurofibromatosis type 1 (NF1) frequently develop plexiform neurofibromas (PNs), which can cause significant morbidity. We performed a phase II trial of the MAPK\/ERK kinase inhibitor, mirdametinib (PD-0325901), in patients with NF1 and inoperable PNs. The primary objective was response rate based on volumetric magnetic resonance imaging analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Inclusion criteria included age \u2265 16 years and a PN that was either progressive or causing significant morbidity. First-dose pharmacokinetics were performed. Patients completed patient-reported outcome measures. Patients received mirdametinib by mouth twice a day at 2 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \/dose (maximum dose = 4 mg twice a day) in a 3-week on\/1-week off sequence. Each course was 4 weeks in duration. Evaluations were performed after four courses for the first year and then after every six courses. Patients could receive a maximum of 24 total courses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Nineteen patients were enrolled, and all 19 received mirdametinib. The median age was 24 years (range, 16-39 years); the median baseline tumor volume was 363.8 mL (range, 3.9-5,161 mL). Eight of the 19 patients (42%) achieved a partial response of the target PN by course 12, and 10 (53%) had stable disease. One patient (5%) developed progressive disease at course 8. Significant and durable decreases were observed in pain ratings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      To our knowledge, this analysis represents the first characterization of the activity and pharmacokinetics of mirdametinib in patients with NF1 and PNs and is the first published response study for MAPK\/ERK kinase inhibitors in adults with NF1 and PNs. Mirdametinib given at 2 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \/dose (maximum dose, 4 mg) twice daily in a 3-week on\/1-week off sequence resulted in a 42% partial response rate with preliminary evidence of reduction in pain.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.20.02220","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T16:02:47Z","timestamp":1611849767000},"page":"797-806","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":135,"title":["NF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults With NF1-Related Plexiform Neurofibromas"],"prefix":"10.1200","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5154-3134","authenticated-orcid":false,"given":"Brian 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