We report a case of an adolescent with treatment-refractory non-rhabdomyosarcoma soft tissue sarcomas, carrying a novel DCTN1–NTRK1 gene fusion...He responded quickly to larotrectinib with the improvement of symptoms and reduction of masses. However, this response was short-lived due to the development of acquired solvent front resistance mutation. This patient did not respond to next-generation TRK inhibitor selitrectinib and eventually succumbed to his disease.