The patient was a girl aged 2 years at the time of enrollment with an ETS variant 6 (ETV6)–neurotrophic receptor tyrosine kinase 3 (NTRK3) fusion, localized, infantile fibrosarcoma…She received vincristine, actinomycin D, and cyclophosphamide (VAC) for 2 cycles and experienced disease progression...therefore she was enrolled into the phase 1 larotrectinib trial. After 4 cycles of larotrectinib, the patient achieved a confirmed partial response with a 52% reduction in tumor burden.

A male infant born with a large congenital IFS of the tongue had the tumour surgically resected at age 4 days....Selective TRK inhibition by larotrectinib offers a novel, highly specific and highly effective therapeutic option for IFS carrying the characteristic ETV6-NTRK3 gene fusion.

We report a case of refractory IFS with constitutive activation of the tropomyosin-related kinase (TRK) signaling pathway from an ETS variant gene 6-neurotrophin 3 receptor gene (ETV6-NTRK3) gene fusion. The patient enrolled in a pediatric Phase 1 trial of LOXO-101, an experimental, highly selective inhibitor of TRK. The patient experienced a rapid, radiographic response, demonstrating the potential for LOXO-101 to provide benefit for IFS harboring NTRK gene fusions.