Phase II study of selpercatinib in children and young adults with RET-altered tumors: Arm N of the NCI-COG Pediatric MATCH trial (APEC1621)

BACKGROUND: This is a phase II subprotocol of the National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice (MATCH) precision oncology platform trial evaluating selpercatinib, a RET inhibitor, in children and young adults aged 1-21 years with relapsed or refractory solid tumors with RET alterations. METHODS: Selpercatinib was given at 90 mg/m2/dose (maximum dose 160 mg/dose) orally twice daily for 28-day cycles until progression or intolerable toxicity. The primary aim was to determine the objective response rate (ORR) and secondary objectives included assessing the tolerability of selpercatinib and estimating the progression-free survival (PFS). RESULTS: Two patients with papillary thyroid carcinomas harboring CCD6C-RET fusions matched to the subprotocol. One patient was deemed ineligible as they had not yet experienced tumor recurrence. The other patient enrolled and received selpercatinib at 90 mg/m2/dose, completing all 26 cycles of protocol therapy and achieving a Partial Response confirmed by central imaging review. There were no dose-limiting toxicities, and the patient experienced only grade 1 adverse events (AEs) attributable to selpercatinib. CONCLUSION: There was a low match and accrual rate on this MATCH subprotocol, resulting in early termination of the study. The basis for low accrual was likely multifactorial, including the overall rarity of this genetic alteration across pediatric tumor types and accelerated FDA approval of selpercatinib in children ≥ 12 years old prior to the opening of this subprotocol. CLINICALTRIALS.GOV IDENTIFIER: NCT04320888. ‡PRINCIPAL INVESTIGATOR: Andrea T. Franson MD MS. IRB APPROVED: Initial September 14, 2020.