Phase I study of ceritinib in pediatric patients (Pts) with malignancies harboring a genetic alteration in ALK (ALK+): Safety, pharmacokinetic (PK), and efficacy results.

10005 Background: Ceritinib is a potent ALK inhibitor with durable efficacy in adult pts with ALK-translocated non-small cell lung cancer. This report describes the results of a phase I study (NCT01742286) in pediatric pts with ALK-aberrant malignancies: anaplastic large cell lymphoma (ALCL); myofibroblastic tumor (MT)/inflammatory (IMT) rhabdomyosarcoma (RMS) and neuroblastoma (NB). In these tumors ALK aberrations differ: ALCL and IMT carry gene translocations, NB amplifications or mutations, and RMS copy number gain or no change. Methods: This trial enrolled pediatric pts ≥ 1 to <18 yrs. ALK gene aberration was required, except in ALCL and RMS, where ALK+ by immunohistochemistry was sufficient. In a fasted, dose-escalation phase, pts received ceritinib at 300–560 mg/m2/day to determine the recommended dose for expansion (RDE). Pts were assessed for safety, PK and efficacy. Results: Twenty-two pts were enrolled (22 centers in 10 countries) over 13 months including: 2 ALCL, 6 IMT, 1 MT, 7 NB, 6 RMS. Media...