Selpercatinib (selective RET inhibitor) posts 53% ORR with 2-year durability in pediatric RET-altered tumors

Selpercatinib is an oral, CNS-active, highly selective RET tyrosine kinase inhibitor evaluated in the multicenter Phase I/II LIBRETTO-121 trial (NCT03899792) in children/adolescents/young adults age 0.5–21 with advanced RET-altered solid tumors (data cutoff November 8, 2024; treated n=36; medullary thyroid cancer [MTC] n=15, RET fusion+ papillary thyroid cancer [PTC] n=15, other n=6). IRC-assessed ORR was 53% (19/36; 95% CI 36–70), including 60% in MTC (9/15) and 53% in PTC (8/15); the 24-month duration-of-response rate was 100% (95% CI 100–100), though interpret cautiously given the small n and immaturity of long follow-up. Safety was consistent with RET inhibition (diarrhea, nausea, transaminase elevations, pyrexia, abdominal pain, headache, cough, vomiting), with no treatment discontinuations due to treatment-related AEs—an appealing tolerability profile vs historical multi-kinase inhibitors often limited by hypertension/hand–foot syndrome and dose interruptions in thyroid cancer.