Data from Pilot Study of Recurrent Ewing's Sarcoma Management with Vigil/Temozolomide/Irinotecan and Assessment of Circulating Tumor (ct) DNA

Abstract

<div>AbstractBackground:<p>Treatment options for recurrent or refractory Ewing's sarcoma (ES) are limited. Vigil is a novel autologous tumor cell therapy expressing bi-shRNA furin/GMCSF plasmid, which previously demonstrated monotherapy activity in advanced ES. Herein we report safety and evidence of benefit to Vigil for ES as potential treatment.</p>Patients and Methods:<p>In this pilot trial, eligible patients with recurrent or refractory ES who failed initial standard-of-care therapy received treatment with temozolomide (TEM) 100 mg/m<sup>2</sup>/day oral and irinotecan (IRI) 50 mg/m<sup>2</sup>/day oral, Days 1 to 5, in combination with Vigil (1 × 10<sup>6</sup>–10<sup>7</sup> cells/mL/day intradermal, Day 15), every 21 days (Vigil/TEM/IRI). Objective response rate (ORR) by RECIST v1.1, progression-free survival (PFS), and overall survival (OS) were assessed. Circulating tumor (ct) DNA analysis was done by patient-specific droplet digital PCR on baseline and serially collected on-treatment samples.</p>Results:<p>Eight of 10 enrolled patients were evaluable for safety and efficacy (mean age 24.6; 12.6–46.1 years old); 2 did not receive Vigil. Seven of 8 patients previously received TEM/IRI. No Vigil-related adverse events were reported. Common ≥Grade 3 chemotherapy-related toxicity included neutropenia (50%) and thrombocytopenia (38%). We observed two partial response patients by RECIST; both showed histologic complete response without additional cancer therapy. Median PFS was 8.2 months (95% confidence interval, 4.3–NA). Five patients showed stable disease or better for ≥6 months. Patient-specific <i>EWS/FLI1</i> ctDNA was detectable in all 8 evaluable patients at baseline. Changes in ctDNA levels corresponded to changes in disease burden.</p>Conclusions:<p>Results demonstrated safety of combination Vigil/TEM/IRI.</p></div>