A Trial For Participants With Ewing's Sarcoma Treated With Vigil in Combination With Irinotecan and Temozolomide

This was a multicenter, Phase III study in participants with metastatic Ewing's sarcoma Family of Tumors (ESFT) refractory/intolerant or recurrent to 1 prior line of chemotherapy. Participants who agreed to participation had tumor tissue harvested from a scheduled standard surgical procedure (e.g., tumor biopsy or palliative resection). The tumor tissue removed was shipped to Gradalis, Inc. to attempt to manufacture the investigational product, Vigil. Subjects who met eligibility criteria including manufacture of a minimum of 4 doses of Vigil were randomized 1:1 to either Group A (Vigil + Irinotecan + Temozolomide (Tem/Iri)) or Group B (Irinotecan + Temozolomide). Screening for the main portion of the study occurred as early as one week but no later than 8 weeks following tumor procurement. Subjects received repeat cycles of treatment until disease progression, unacceptable toxicity, withdrawal of consent or other criterion was met for discontinuation from study. Subjects randomized to Group A (Vigil + Tem/Iri) received up to 12 doses depending upon the quantity of Vigil manufactured from the surgical specimen. 1 cycle = 21 days. If irinotecan + temozolomide was administered beyond 12 cycles, it was administered off study. Subjects randomized to Group B (Tem/Iri) may have crossed over to receive single agent Vigil every 21 days following End of Treatment assessment and documented disease progression confirmed by central radiology vendor, for up to 12 doses of Vigil depending upon the quantity of Vigil manufactured. Participants were managed in an outpatient setting. Hematologic function, liver enzymes, renal function and electrolytes will be monitored. Blood for immune function analyses including IFNγ-ELISPOT analysis of cytotoxic T cell activation in response to autologous tumor antigens will be collected at tissue procurement, post-procurement screening and Day 1 (prior to chemotherapy administration) at Cycles 2, 4, and 6, end of treatment (EOT), 3 months after EOT, and every 6 months thereafter. Blood for ctDNA analysis was collected at tissue procurement, prior to chemotherapy administration at baseline and on Day 1 prior to chemotherapy administration at Cycles 2, 3, 4, and 6, and EOT. After progression, participants were contacted quarterly for documentation of post study therapies and survival status information.