A patient with metastatic relapsed Ewing sarcoma, zccs505, with an EWSR1–FLI1 gene fusion and previous disease progression following radiotherapy and irinotecan/temozolomide (IRN/TMZ) experienced CR following treatment with cyclophosphamide/topotecan (cyclo/topo) and cyclo/topo in combination with the multi-tyrosine kinase inhibitor cabozantinib, which was identified and informed by single-agent HTS (Supplementary Fig. S2). Here, EWSR1 is linked to Ewing sarcoma.