{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:56:43Z","timestamp":1791565003002,"version":"4.3.4"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>APEC1621 arm M, a subprotocol of the NCI-COG Pediatric MATCH clinical trial, is a phase 2 study evaluating tipifarnib, a farnesyl transferase inhibitor, in patients with relapsed or refractory solid tumors harboring HRAS mutations at codons G12, G13, Q61, or A146 (NCT04284774).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients identified by the MATCH screening protocol and enrolled to the arm M subprotocol received tipifarnib at 350\u2009mg\/m2\/dose (maximum 600\u2009mg\/dose) orally twice daily on an intermittent dosing schedule (days 1 to 7 and 15 to 21, every 28 days) until disease progression or intolerable toxicity. The primary aim was to determine the objective response rate (ORR) and secondary objectives included estimating progression-free survival (PFS) and assessing the tolerability of tipifarnib on the intermittent dosing schedule in children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seven patients matched to the tipifarnib subprotocol and five patients (71%) enrolled. Two matched patients were ineligible for treatment. Diagnoses for the enrolled patients were rhabdomyosarcoma (n\u2009=\u20094) and angiosarcoma (n\u2009=\u20091). HRAS mutations identified in those tumors included G13R (n\u2009=\u20092) and G12S, G12C, and Q61L (n\u2009=\u20091 each). Treatment was associated with grade 1\/2 adverse events (AE) consistent with those expected from prior studies. Grade 3 or higher AEs on treatment were disease progression, dyspnea, and pleural effusion, not related to protocol therapy. One patient had stable disease (SD) at the end of cycle two and remained on protocol therapy for four cycles. There were no objective responses (OR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This U.S. cooperative group study was successful at identifying pediatric patients with tumors that harbored oncogenic mutations in HRAS. The frequency of the mutations identified and patients enrolled was lower than anticipated and the study closed before accrual was complete. The adverse effect profile of tipifarnib in pediatric patients on the intermittent dosing schedule was acceptable. Limited single-agent efficacy of tipifarnib was observed in this biomarker-selected cohort of refractory pediatric tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag401","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:51:56Z","timestamp":1791546716000},"source":"Crossref","is-referenced-by-count":0,"title":["A phase 2 study of tipifarnib in children and young adults with tumors harboring HRAS genomic alterations: NCI-COG Pediatric MATCH trial (APEC1621M)"],"prefix":"10.1093","author":[{"given":"Christine A","family":"Pratilas","sequence":"first","affiliation":[{"name":"Johns Hopkins University , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielle E","family":"Yohe","sequence":"additional","affiliation":[{"name":"National Institutes of Health Clinical Center , Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P Mickey","family":"Williams","sequence":"additional","affiliation":[{"name":"Frederick National Laboratory for Cancer Research , Frederick, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel M","family":"Reid","sequence":"additional","affiliation":[{"name":"Mayo Clinic Comprehensive Cancer Center , Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Piao","sequence":"additional","affiliation":[{"name":"University of Southern California Keck School of Medicine, , Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Saguilig","sequence":"additional","affiliation":[{"name":"Children's Oncology Group Statistical Center , Monrovia, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Patton","sequence":"additional","affiliation":[{"name":"NCI Center for Biomedical Informatics and Information Technology, , NIH, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent","family":"Coffey","sequence":"additional","affiliation":[{"name":"NCI Center for Biomedical Informatics and Information Technology, , NIH, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd A","family":"Alonzo","sequence":"additional","affiliation":[{"name":"University of Southern California Keck School of Medicine, , Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandria M","family":"Thompson","sequence":"additional","affiliation":[{"name":"Johns Hopkins University , Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Arwood","sequence":"additional","affiliation":[{"name":"Advocate Children\u2019s Hospital , Park Ridge, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinchita","family":"Roy-Chowdhuri","sequence":"additional","affiliation":[{"name":"University of Texas MD Anderson Cancer Center , Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilsa C","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Research Institute at Nationwide Children's Hospital Biopathology Center, , Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey L","family":"Berg","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine , Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Fox","sequence":"additional","affiliation":[{"name":"St. Jude Children\u2019s Research Hospital , Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda J","family":"Weigel","sequence":"additional","affiliation":[{"name":"St. Jude Children\u2019s Research Hospital , Memphis, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas S","family":"Hawkins","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Hospital , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret M","family":"Mooney","sequence":"additional","affiliation":[{"name":"National Cancer Institute Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program, , Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Takebe","sequence":"additional","affiliation":[{"name":"National Cancer Institute Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program, , Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James V","family":"Tricoli","sequence":"additional","affiliation":[{"name":"National Cancer Institute Division of Cancer Treatment and Diagnosis, , Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A","family":"Janeway","sequence":"additional","affiliation":[{"name":"Dana-Farber\/Boston Children\u2019s Cancer and Blood Disorders Center , Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nita L","family":"Seibel","sequence":"additional","affiliation":[{"name":"National Cancer Institute Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program, , Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D William","family":"Parsons","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine , Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,9]]},"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/oncolo\/advance-article-pdf\/doi\/10.1093\/oncolo\/oyag401\/71789098\/oyag401.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/advance-article-pdf\/doi\/10.1093\/oncolo\/oyag401\/71789098\/oyag401.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:25:57Z","timestamp":1791563157000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/advance-article\/doi\/10.1093\/oncolo\/oyag401\/8898734"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,9]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/oncolo\/oyag401","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,9]]},"article-number":"oyag401"}}