Randomized Double-Blind Placebo-Controlled Trial Of Primary Maintenance Vigil Immunotherapy (Vital Study) In Stage Iii/Iv Ovarian Cancer: Efficacy Assessment In Brca1/2-Wt Patients

6017 Background: Vigil is an autologous tumor cell vaccine constructed from autologous harvested tumor tissue transfected with a DNA plasmid encoding GMCSF and bi-shRNA-furin thereby creating TGFβ expression control. Methods: A randomized double-blind placebo-controlled trial of Vigil vs. placebo was performed in advanced stage frontline OC patients. Relapse-free survival (RFS) and safety were endpoints. Patients who achieved complete clinical response were randomized [1:1 to placebo (control group, CG) or Vigil (Vigil group, VG)] after completion of frontline surgery and chemotherapy. All patients received 1 x 10e7 cells/ml of Vigil or placebo intradermally once a month for up to 12 doses. Results: Ninety-two patients were randomized with 91 patients in the per-protocol population (PP), (VG n=46; CG n=45). 62 patients were tested for BRCA1/2 status. VG showed no added overall toxicity compared to CG and no grade 4/5 toxicities were observed. Grade 2/3 toxic events were observed in 18% of CG patients (most common bone pain, fatigue) compared to 8% of VG patients (most common nausea, musculoskeletal pain). From time of randomization median RFS for all 91 patients was favorable in the VG (HR 0.69, one-sided p 0.088).Stratified by BRCA status, an advantage in RFS was seen in the BRCA1/2-wt patients in VG (19.4 mo) compared to CG (8 mo) (HR 0.51, 90% CI 0.26 – 1.01, one-sided p 0.050) from time of randomization and HR of 0.49 (90% CI 0.25 – 0.97, one-sided p 0.038) from time of surgery. Median time from surgery to randomization was 208.5 days (6.9 mo) in VG vs. 200 days (6.6 mo) in CG. 37.5% BRCA1/2-wt Vigil treated patients relapsed compared to 71% of placebo at time of data snap for analysis (HR 0.51, one-sided p 0.05), (median follow-up of 34.3 mo for all n=91 subjects). Germline and somatic BRCA1/2 molecular testing via central third party is underway on all 91 patients under continued blinded conditions to validate activity in BRCA1/2-wt. Conclusions: Vigil immunotherapy as frontline maintenance in Stage III/IV ovarian cancer is well tolerated and showed RFS clinical benefit, particularly in BRCA1/2-wt disease. Clinical trial information: NCT02346747. [Table: see text]