A bi-shRNA furin and GMCSF engineered autologous tumor cell immunotherapy vs. gemcitabine + docetaxel for Ewing sarcoma and with cryoablation in Ewing family tumors

• Published in: Journal of clinical oncology Vol. 35; no. 15_suppl; p. TPS11079
• Main Authors: Anderson, Peter Meade, Ghisoli, Maurizio, Barve, Minal A., Gill, Jonathan Benjamin, Wexler, Leonard H., DeAngulo, Guillermo, Neville, Kathleen, Manning, Luisa, Wallraven, Gladice, Senzer, Neil N., Birkhofer, Martin, Nemunaitis, John J.
• Format: Journal Article
• Language: English
• Published: 20-05-2017
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2017.35.15_suppl.TPS11079

Abstract only TPS11079
Background: Vigil, an immuno-stimulatory autologous cellular therapy, uses patient tumor cells transfected with a plasmid encoding genes for GM-CSF and furin (to down regulate TGFβ 1&2). A Phase I study in relapsed Ewing’s sarcoma. (N = 16) had one 9 month partial response and a two-year survival rate of 44% [1]. Rapid, durable systemic immune activation was seen in the majority of patients using an IFNƔ ELISPOT assay [2]. We seek to extend these early findings in a randomized Phase 2 study (NCT02511132). Methods: Following surgery (for Vigil manufacture), patients are randomized 1:1 to Vigil (1 x 10
7
cells/ml by monthly intradermal injection), or to chemotherapy with gemcitabine 675mg/m2 IV D1 and D8 and docetaxel 75 mg/m2 IV D8 every 21 days. Key eligibility criteria include: Age > 2, histologically documented metastatic Ewing's, refractory or intolerant to ≥2 prior lines of chemotherapy, and availability of at least 4 doses of manufactured Vigil. Patients with bone only disease are ineligible. The primary objective is to compare the overall survival of patients treated with Vigil vs. chemotherapy. The sample size of 62 patients assumes a one-year survival rate of 25% in the chemotherapy group vs. 60% in the Vigil group, corresponding to a hazard ratio of 0.383 favoring Vigil. Results: As of January 2017, thirteen patients have been randomized at 10 centers in the U.S. The design allows for reduction in disease burden prior to surgery using modalities like SBRT and interventional radiology. Toxicity of Vigil has been low compared to chemotherapy. Time to disease progression is being assessed in patients who crossover to Vigil after progressing on chemotherapy. Systemic control of metastatic lesions using cryoablation is also being assessed in other patients (e.g. DSRCT liver metastases) using a separate IND. Conclusions: Although associated with systemic immune activation, additional means to reduce disease burden such as SBRT and cryoablation can possibly improve patient health and augment Vigil efficacy. References: 1.Ghisoli M, Barve M, et al. Mol Ther. 2016 Apr 25 2. Oh J, Barve M, et al. Gynecologic Oncology 2016; 143: 504–510. Clinical trial information: NCT02511132.