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)
Objective
Primary Objectives Phase 1:
Evaluate the safety and tolerability at different dose levels of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring anaplastic lymphoma kinase (ALK), receptor tyrosine kinase encoded by the gene ROS1 (ROS1), or neurotrophic receptor kinase genes encoding TRK kinase family (NTRK1-3) alterations to estimate the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) and select the Pediatric Recommended Phase 2 Dose (RP2D)/schedule.
Phase 2: Determine the anti-tumor activity of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring ALK, ROS1, or NTRK1-3 alterations.
Secondary Objectives: Phase 1: Characterize the pharmacokinetics (PK) of repotrectinib in pediatric and young adult subjects with advanced malignancies with ALK, ROS1, or NTRK1-3 alterations.
Determine the preliminary anti-tumor activity of repotrectinib in pediatric subjects with advanced malignancies with ALK, ROS1, or NTRK1-3 alterations.
Phase 2: Determine the anti-tumor activity in terms of DOR, overall survival (OS) and progression- free survival (PFS) following treatment with repotrectinib.
Determine intracranial anti-tumor activity of repotrectinib.
Evaluate the safety and tolerability of repotrectinib at the pediatric RP2D. Characterize the PK of repotrectinib at the pediatric RP2D.
