FLORA-5/GOG3035: Frontline chemo-immunotherapy (paclitaxel-carboplatin-oregovomab [PCO] versus chemotherapy (paclitaxel-carboplatin-placebo [PCP]) in patients with advanced epithelial ovarian cancer (EOC)—Phase III, double-blind, placebo-controlled, global, multinational study.

Angeles Alvarez Secord Duke Cancer Institute, Duke University Medical Center, Durham, NC info_outline Angeles Alvarez Secord, Lisa Marie Barroilhet, Myong Cheol Lim, Sunil Gupta, Sonia Oosman, Jada Srinivas Rao, John O. Schorge, Joyce N. Barlin, Lucy Gilbert, Devansu Tewari, Michael Gold, Diane M. Provencher, JUNG-YUN LEE, Kristin Leigh Bixel, Eduardo Yañez, Lukas Rob, David M. O'Malley

Authors Angeles Alvarez Secord Duke Cancer Institute, Duke University Medical Center, Durham, NC info_outline Angeles Alvarez Secord, Lisa Marie Barroilhet, Myong Cheol Lim, Sunil Gupta, Sonia Oosman, Jada Srinivas Rao, John O. Schorge, Joyce N. Barlin, Lucy Gilbert, Devansu Tewari, Michael Gold, Diane M. Provencher, JUNG-YUN LEE, Kristin Leigh Bixel, Eduardo Yañez, Lukas Rob, David M. O'Malley Organizations Duke Cancer Institute, Duke University Medical Center, Durham, NC, University of Wisconsin Carbone Cancer Center, Madison, WI, National Cancer Center, Goyang-Si, Gyeonggi-Do, South Korea, OncoQuest Pharma USA, Inc., Wilmington, DE, OncoQuest Pharmaceticals, Inc, Jersey City, NJ, OncoQuest Pharmaceuticals, Inc, Singapore, Singapore, Massachusetts General Hospital, Boston, MA, Womens Cancer Care Assoc, Albany, NY, McGill University Health Centre, Royal Victoria Hospital, Montréal, QC, Canada, Kaiser Permanente, Newport Coast, CA, Oklahoma Cancer Specialists and Research Institute, Tulsa, OK, University of Montreal, Montreal, QC, Canada, Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, South Korea, The Ohio State University Wexner Medical Center and James Cancer Hospital, Columbus, OH, Medical Oncology, Universidad de la Frontera, Temuco, Chile, Department of Obstetrics and Gynaecology, University Hospital Kralovske Vinohrady, Prague, Czech Republic Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: Oregovomab, a murine IgGκ1 monoclonal antibody, has high affinity binding to tumor associated antigen CA125, thus, 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 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 PC, HR O.35, p=0.043) in patients with previously untreated EOC. 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: The study is a 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, and Chile. 179 patients were enrolled at time of submission. Clinical trial information: NCT04498117.