TPX-0005 (Repotrectinib), a next-generation ALK/ROS1/NTRK1–3 inhibitor, has potent antiproliferative and anti-tumor activity as monotherapy and in combination with chemotherapy in neuroblastoma cell lines and pediatric patient derived xenograft models

Background: Abnormal activation of the ALK tyrosine kinase receptor drives the malignant behavior of many pediatric cancer subtypes, including neuroblastoma. Somatic ALK mutations have been reported in 6–10% of patients with neuroblastoma. Patients with relapsed and refractory disease have poor outcomes despite multimodal treatment with chemotherapy, immunotherapy, radiation, and surgery; thus, this population is in dire need of novel and less toxic therapies. TPX-0005 (Repotrectinib) is a novel multityrosine kinase inhibitor that selectively targets ALK, ROS1, and NTRK1-3 (including solvent-front and gatekeeper mutations) as well as accessory pathways including JAK/STAT and SRC/FAK, that are implicated in oncogenesis. Therefore, TPX-0005 could be a promising novel therapeutic option for patients with ALK-mutant neuroblastoma.