Multinational phase 1-2 study of selpercatinib for RET-altered solid tumors in children and adolescents

Selpercatinib, a highly selective oral RET inhibitor with CNS activity, has previously demonstrated durable responses and acceptable safety in adults with RET-driven cancers. The multinational phase 1-2 LIBRETTO-121 study of selpercatinib for RET-altered advanced solid tumors in children and adolescents has now been published. A total of 36 patients aged 2 to 20 years were treated. 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 treament-related adverse events were observed. Objective response rate by independent review committee was 53% (95% CI 36-70); among patients with MTC and PTC, ORR by IRC was 60% (32-84) and 53% (27-29), respectively. The 24-month duration of response was 100%. The authors conclude that selpercatinib showed durable efficacy in pediatric or adolescent patients with RET-altered thyroid cancer and was well tolerated.