Clinical trial in progress: A phase 3 study of maintenance bi-shRNA-furin/GM-CSF-expressing autologous tumor cell vaccine in women with stage IIIb-IV high-grade epithelial ovarian cancer.

Abstract

TPS5604 Background: Vigil is an immuno-stimulatory autologous cellular therapy, which uses patient tumor cells transfected with a plasmid encoding genes for GM-CSF and furin (to down regulate TGFβ 1&2). In Phase I, systemic immune activation was demonstrated in the majority of patients using an IFNƔ ELISPOT assay. A randomized Phase 2 assessment of Vigil maintenance therapy vs. observation in ovarian cancer demonstrated prolonged relapse free survival (RFS) (Oh J, Barve M, et al. Gynecologic Oncology, 2016; 143: 504–510.). Based on these observations, a Phase 3 study of maintenance Vigil therapy in patients with advanced ovarian cancer was initiated (NCT02346747). Methods: This is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 study of maintenance Vigil in women with Stage IIIb,c or IV high-grade papillary serous/clear cell/ endometrioid ovarian, fallopian tube or primary peritoneal cancer. Patients will have a minimum of 4 and a maximum of 12 Vigil doses manufactured from tumor obtained at primary debulking surgery. Patients must achieve a complete clinical remission following primary surgery and chemotherapy before being randomized 1:1 to receive either monthly intradermal Vigil or placebo. Randomization is stratified by extent of surgical cytoreduction (complete/microscopic vs. macroscopic residual disease) and neoadjuvant vs. adjuvant chemotherapy. The primary objective is to compare RFS of subjects randomized to Vigil vs. placebo, and the key secondary objective is overall survival (OS). The sample size calculation of 222 patients assumes 24 months for accrual and 36 months of follow-up with a median RFS of 19 months from randomization, in the control group. This provides 90% power to detect a hazard ratio (HR) of 0.6 favoring Vigil at the 0.05 level of significance. To date, 61 patients have been randomized and an additional 55 patients are receiving chemotherapy in anticipation of randomization. Tumor tissue is being obtained from approximately 20 patients per month at multiple sites across the U.S. At their last meeting in January, 2017 the independent DSMB recommended that the study continue without change. Clinical trial information: NCT02346747.