A 41-year-old Asian female never-smoker presented with stage IV NSCLC...A repeat biopsy and comprehensive genomic profiling at Foundation Medicine revealed CD74–ROS1 and a ROS1 G2032R SFM. The patient subsequently enrolled on the phase I repotrectinib trial and received repotrectinib at 160 mg once daily...A confirmed PR (−36.6%) by RECIST v1.1 was achieved with a duration of response of 7.4 months. Of note, this patient also responded to repotrectinib in the CNS for 9 months with subsequent CNS-only progression controlled by whole-brain radiation (WBRT) with continuation of repotrectinib during WBRT without any adverse events.