{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:45:34Z","timestamp":1792010734813,"version":"4.4.0"},"reference-count":29,"publisher":"American Society of Clinical Oncology (ASCO)","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Selpercatinib, a highly selective oral RET inhibitor with CNS activity, has previously demonstrated durable responses and an acceptable safety profile in adults with\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      -driven cancers. Consequently, the safety and efficacy of selpercatinib were investigated in pediatric\/adolescent participants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      LIBRETTO-121 (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\/NCT03899792\">NCT03899792<\/jats:ext-link>\n                      ) was a multicenter phase I\/II trial of selpercatinib in participants age 0.5-21 years with advanced,\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      -altered solid tumors. In phase I, the primary end point was safety, including dose-limiting toxicities. In phase II, the primary end point was objective response rate (ORR) as determined by independent review committee (IRC) per RECIST v1.1. Key secondary end points included ORR by investigator, duration of response (DOR), progression-free survival, overall survival, safety, and pharmacokinetics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      As of November 8, 2024, 36 participants age 2-20 years were treated with selpercatinib. Tumor types included\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      -altered medullary thyroid cancer (MTC, n = 15),\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      fusion\u2013positive papillary thyroid cancer (PTC, n = 15), and other (n = 6). The most common treatment-emergent adverse events were diarrhea, nausea, elevated AST, pyrexia, abdominal pain, elevated ALT, headache, cough, and vomiting. No treatment discontinuations due to treatment-related adverse events or new adverse drug reactions were observed. ORR by IRC was 53% (19\/36; 95% CI, 36 to 70). For participants with MTC and PTC, ORR by IRC was 60% (9\/15; 95% CI, 32 to 84) and 53% (8\/15; 95% CI, 27 to 79), respectively. The 24-month DOR rate was 100% (95% CI, 100 to 100).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Selpercatinib showed durable efficacy in pediatric\/adolescent participants with\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      -altered thyroid cancer and was well tolerated, supporting targeting of\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      alterations in pediatric\/adolescent patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-03013","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:59:23Z","timestamp":1792007963000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Selpercatinib in Pediatric and Adolescent Patients With\n                    <i>RET<\/i>\n                    -Altered Solid Tumors: Safety and Efficacy Results From the Phase I\/II LIBRETTO-121 Study"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8497-3138","authenticated-orcid":false,"given":"Theodore W.","family":"Laetsch","sequence":"first","affiliation":[{"name":"Children's Hospital of Philadelphia\/University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyoung Jin","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, Seoul National University Children's Hospital, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Casanova","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, 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