{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T21:22:34Z","timestamp":1785792154051,"version":"3.56.0"},"reference-count":35,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"8","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> The National Cancer Institute-Children's Oncology Group (NCI-COG) Pediatric MATCH trial assigns patients age 1-21 years with refractory malignancies to phase II treatment arms of molecularly targeted therapies on the basis of genetic alterations detected in their tumor. Patients with activating alterations in the mitogen-activated protein kinase pathway were treated with ulixertinib, an extracellular signal-regulated kinase (ERK)1\/2 inhibitor. <\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p> As there were no previous pediatric data, ulixertinib was initially tested in a dose escalation cohort to establish the recommended phase II dose (RP2D) before proceeding to the phase II cohort. Ulixertinib was administered at 260 mg\/m<jats:sup>2<\/jats:sup>\/dose orally twice a day (dose level 1 [DL1], n = 15) or 350 mg\/m<jats:sup>2<\/jats:sup>\/dose orally twice a day (DL2, n = 5). The primary end point was objective response rate; secondary end points included safety\/tolerability and progression-free survival (PFS). <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> Twenty patients (median 12 years; range, 5-20) were treated, all evaluable for response. CNS tumors comprised 55% (11\/20) of diagnoses, with high-grade glioma and low-grade glioma most common (n = 5 each). All CNS tumors except one harbored BRAF fusions or V600E mutations. Rhabdomyosarcoma (n = 5) was the most frequent non-CNS diagnosis. DL1 was declared the RP2D in the dose escalation cohort after dose-limiting toxicities in Cycle 1 occurred in 1\/6 patients at DL1 and 2\/5 patients at DL2, including fatigue, anorexia, rash, nausea, vomiting, diarrhea, dehydration, hypoalbuminemia, and hypernatremia. No objective responses were observed. Six-month PFS was 37% (95% CI, 17 to 58). Three patients with BRAF-altered CNS tumors achieved stable disease &gt;6 months. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> Ulixertinib, a novel targeted agent with no previous pediatric data, was successfully evaluated in a national precision medicine basket trial. The pediatric RP2D of ulixertinib is 260 mg\/m<jats:sup>2<\/jats:sup>\/dose orally twice a day. Limited single-agent efficacy was observed in a biomarker-selected cohort of refractory pediatric tumors. <\/jats:p><\/jats:sec>","DOI":"10.1200\/po.24.00103","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T20:06:53Z","timestamp":1719518813000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":13,"title":["Phase II Study of Ulixertinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Alterations: APEC1621J of the National Cancer Institute-Children's Oncology Group Pediatric MATCH Trial"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9281-7485","authenticated-orcid":true,"given":"Kieuhoa T.","family":"Vo","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of California, San Francisco School of Medicine, UCSF Benioff Children's Hospital, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2061-5139","authenticated-orcid":true,"given":"Amit J.","family":"Sabnis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San Francisco School of Medicine, UCSF Benioff Children's Hospital, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3309-5988","authenticated-orcid":true,"given":"P. 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