Selpercatinib in Pediatric and Adolescent Patients With RET -Altered Solid Tumors: Safety and Efficacy Results From the Phase I/II LIBRETTO-121 Study

PURPOSE Selpercatinib, a highly selective oral RET inhibitor with CNS activity, has previously demonstrated durable responses and an acceptable safety profile in adults with RET -driven cancers. Consequently, the safety and efficacy of selpercatinib were investigated in pediatric/adolescent participants. METHODS LIBRETTO-121 (ClinicalTrials.gov identifier: NCT03899792 ) was a multicenter phase I/II trial of selpercatinib in participants age 0.5-21 years with advanced, RET -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. RESULTS As of November 8, 2024, 36 participants age 2-20 years were treated with selpercatinib. Tumor types included RET -altered medullary thyroid cancer (MTC, n = 15), RET fusion–positive 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). CONCLUSION Selpercatinib showed durable efficacy in pediatric/adolescent participants with RET -altered thyroid cancer and was well tolerated, supporting targeting of RET alterations in pediatric/adolescent patients.