FLORA-5/GOG3035: Chemo-immunotherapy (paclitaxel-carboplatin-oregovomab [PCO] vs chemotherapy (paclitaxel-carboplatin-placebo [PCP]) as front-line treatment in patients with advanced epithelial ovarian cancer (EOC)-Phase III, double blind, placebo controlled, global, multinational study

TPS5625 Background: Oregovomab, a murine IgGκ1 monoclonal antibody with high affinity binding to tumor associated antigen CA125, renders the target antigen CA125 more immunogenic or “neoantigen-like”. The proposed mechanism action is enhanced antigen processing and presentation to specific T cells. This phenomenon is hypothesized to bypass tumor-associated immune suppression when oregovomab is combined with chemotherapy. In a randomized phase II study, oregovomab, in combination with paclitaxel and carboplatin, (PC) induced tumor immunity and demonstrated significant improvement in median PFS (41.8 months(m) PCO vs 12.2 m PC, HR 0.46, p = 0.0027) and median OS (N.E. PCO vs 43.2 m PCP, HR 0.35, p = 0.043) in patients with previously untreated EOC. Patients receiving adjuvant chemotherapy were included. Oregovomab combined with PC had a favorable toxicity profile. FLORA-5/GOG3035, the definitive confirmatory global registration trial, is currently recruiting patients in the front-line setting. Methods: In this phase 3, multicenter, double-blind, placebo-controlled trial, optimally debulked patients with FIGO III/IV EOC and serum CA125 ≥ 50 U/ml receiving adjuvant (Cohort 1) or patients receiving neoadjuvant chemotherapy post-interval cytoreductive surgery (Cohort 2) will be randomized to PC + oregovomab or placebo (PCO vs. PCP). Patients with germline BRCA1/2 mutations are excluded. Chemotherapy will be administered every 3 weeks in both cohorts. Oregovomab/placebo is administered simultaneously at cycles 1, 3, and 5 of chemotherapy with an additional dose at 12 weeks following cycle 5 in Cohort 1. Neoadjuvant patients will be administered oregovomab/placebo after debulking surgery at cycles 4 and 6 with two additional doses at 6- and 18-weeks following cycle 6 in Cohort 2. No other front-line maintenance therapy is permitted. The primary objective is PFS determined by RECIST 1.1. Cohort 1 will recruit 372 patients with a 90% power to detect a difference with an alpha of 0.025 and a hazard ratio of 0.65 when 252 PFS events have been observed. Cohort 2 will be analyzed separately recruiting 232 patients with a 90% power to detect a difference with an alpha of 0.025 and a hazard ratio of 0.60 when 165 PFS events have been observed. An interim futility analysis will be performed. Secondary objectives include OS, frequency and severity of AEs, and QoL. Exploratory objectives include iRECIST, TFST, TSST, PFS2, and evaluation of correlative biomarkers. The study is actively enrolling in the US, Canada, Belgium, Italy, Spain, Czech Republic, Hungary, Poland Korea, Taiwan, Mexico Argentina, India and Chile. 518 of the planned 602 patients were enrolled at the time of submission. Clinical trial information: NCT04498117 .