Objective: LX-101, a next-generation, targeted therapy directed to the insulin-like growth factor 1 receptor (IGF-1R), consists of a proprietary IGF-1 variant coupled to a cytotoxic methotrexate (MTX) payload. These results demonstrate that LX-101 has potent preclinical anti-tumor activity against pediatric sarcoma cell lines with well-established ties to the IGF-1R pathway, including with different oncogenic gene fusions. These data further support the clinical development of LX-101 in IGF-1R-related pediatric cancers. A clinical trial is planned.