FLORA-5: Front-line chemoimmunotherapy (Paclitaxel-Carboplatin-Oregovomab [PCO] versus chemotherapy (Paclitaxel-Carboplatin-Placebo [PCP]) in patients with advanced epithelial ovarian cancer (EOC)—Phase III double-blind placebo controlled multinational study.

TPS5606 Background: Oregovomab binds tumor-associated CA125 rendering the target antigen CA125 more immunogenic or “neoantigen-like” through altered and enhanced antigen processing and presentation to specific T cells. This phenomenon is hypothesized to bypass tumor-associated immune suppression when administered in combination with chemotherapy. In a randomized phase II study, immunization with oregovomab in a schedule-dependent combination with paclitaxel and carboplatin induced tumor immunity and demonstrated significant improvement in PFS (median (months) 41.8 PCO vs 12.3 PCP, HR 0.44 p = 0.0027, and OS median N.E. PCO vs 43.2 PCP HR O.34 (p = 0.0077)) in patients with previously untreated EOC. The FLORA-5, the definitive confirmatory global registration trial, is currently recruiting patients in the front-line setting. Methods: The study is a phase 3, multicenter, double-blind, placebo-controlled clinical trial. Optimally debulked patients with FIGO III/IV EOC and serum CA125 > 50 U/ml receiving adjuvant (Cohort 1) or neoadjuvant (Cohort 2) chemotherapy will be randomized post-surgery to paclitaxel and carboplatin with or without oregovomab. Patients with germline BRCA1/2 mutations will be 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 a single maintenance dose at 12 weeks following cycle 5 in Cohort 1. Neoadjuvant patients (Cohort 2) will be administered oregovomab/placebo post interval debulking surgery at cycles 4 and 6 with maintenance doses at 6- and 18-weeks following cycle 6. No other post front-line maintenance therapy is permitted. The primary objective is PFS determined by RECIST 1.1 criteria. 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 analysis for futility will be performed. Secondary objectives include OS, frequency and severity of adverse events, and quality of life. Exploratory objectives include iRECIST, TFST, TSST, PFS2, and evaluation of potential biomarkers. The study is actively enrolling in the US with 9 patients enrolled at time of submission. Centers in Europe, South America and Asia are expected to begin accruing shortly. Clinical trial information: NCT04498117.