2022-RA-800-ESGO AGO-OVAR 27: window-of-opportunity proof-of-concept, non-randomized, open-label phase ii trial of olaparib given alone or in combination with durvalumab prior to primary debulking surgery in histologically proven high-grade epithelial ovarian cancer

Introduction/Background The time window prior to debulking surgery offers a unique opportunity to directly study the response of treatment-naïve epithelial ovarian cancer (EOC) to targeted therapies alone or in combinations and to obtain serial tissue and liquid biopsies to study clinically useful predictive biomarkers, e.g. for poly-ADP-ribose-polymerase (PARP) inhibitors and/or immune checkpoint inhibitors. As distinct from a neoadjuvant concept, the observed effect will not be obscured by highly effective platinum-based chemotherapy. Methodology This proof-of-concept, non-randomized, open-label, phase II trial of Olaparib alone (cohort A) or in combination with Durvalumab (cohort B) prior to primary debulking surgery in histologically proven high-grade EOC evaluates the feasibility of the window-of-opportunity (WoO) procedure. Patients with suspected advanced high-grade EOC scheduled to undergo diagnostic laparoscopy for histologic confirmation will be registered into the trial. Only those deemed candidates for primary debulking surgery and with histologically confirmed diagnosis of high-grade EOC, fulfilling all other inclusion criteria, will then be included in the WoO treatment phase. WoO treatment phase will be followed by primary debulking surgery and standard-of-care platinum-based first-line chemotherapy and maintenance therapy. Fresh-frozen and corresponding Formalin-fixed-paraffin-embedded (FFPE) tumor samples will be obtained for translational research at laparoscopy and primary debulking surgery. Plasma samples for circulating tumor DNA (ctDNA) analysis and plasma/serum samples for further translational research analyses will be obtained during all phases of the study at defined time points. It is planned to enroll 30 patients per cohort. After completion of cohort A, a trial steering committee will review safety and feasibility prior to starting cohort B. Further information: NCT04644289. Results The first patient has been enrolled recently. Conclusion This concept might open the possibility to investigate the predictive value of biomarkers for benefit from PARP and immune-checkpoint inhibitors in the treatment of EOC. Sponsor: AGO Study Group. Financial support and drug supply: AstraZeneca.