A Phase 1/2, Open-label, Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity Study of Repotrectinib in Pediatric and Young Adult Subjects with Advanced or Metastatic Malignancies Harboring ALK, ROS1, or NTRK1-3 Alterations (CARE)

A child or young adult with a rare, treatment-resistant cancer will receive an experimental drug called repotrectinib, taken daily as a pill, to see if it shrinks their tumour and how well their body tolerates it. This matters because some childhood cancers are driven by specific genetic faults in the ALK, ROS1, or NTRK genes, for which few targeted therapies are approved for young patients. Existing drugs often stop working as tumours develop resistance, or cause side effects that limit their use. Repotrectinib is designed to overcome common resistance mutations and to reach the brain, where these cancers frequently spread. If this trial succeeds, repotrectinib could become a new treatment option for children and young adults with these rare malignancies, offering a targeted alternative to broad chemotherapy. For the small number of patients whose cancers harbour these alterations, the impact could be direct and personal: more time with fewer side effects, and a drug that works even after others have failed. The study is a necessary step before the drug can be considered for routine NHS use.