Phase I clinical trial - Pédiatrie Neuroblastomes

Common genes implicated in high-risk neuroblastoma such as ALK, LIN28B, and AURKA;(Aurora kinase A) are involved in stabilizing and increasing expression of N-MYC protein;(Molenaar et al. 2012; Schnepp et al. 2015; Matthay et al. 2016). The relationship between;AurA and N-Myc/Myc in neuroblastoma includes both a protein stabilization interaction (Otto et;al. 2009) and direct transcriptional control (B³chel et al. 2017), suggesting that neuroblastoma;and other MYC-driven tumors are particularly sensitive to AurA inhibition. Furthermore, AurA;is considered a promising clinical therapeutic target for neuroblastoma and other MYC-driven;tumors (DÀAssoro et al. 2015; Damodaran et al. 2017).;LY3295668 erbumine (hereinafter referred to as LY3295668) is a highly selective AurA;inhibitor (Gong et al. 2019). Study J1O-MC-JZHD (JZHD) is designed to assess the safety and;tolerability to identify the recommended Phase 2 dose of LY3295668 erbumine administered as;monotherapy and in combination with topotecan and cyclophosphamide in pediatric patients;with relapsed/refractory neuroblastoma.