TPS5628 Background: PAOLA-1/ENGOT-ov25 trial demonstrated that Olaparib (O) plus Bevacizumab (B) determined a significant survival benefit in patients (pts) with advanced, high-grade, epithelial ovarian, peritoneal and/or fallopian-tube cancer (HEOC) presenting defects of homologous recombination repair system (HRD+) in clinical response after first-line platinum-based chemotherapy (CT) plus B. Methods: IOLANTHE is a multicenter Italian phase IV trial (sponsored by the MaNGO group, Protocol Number IRFMN-OVA-8542) aiming to confirm in a setting close to clinical practice the efficacy of this combination in pts with HRD+HEOC. As the study includes a consistent translational component, all suspicious advanced cases will be considered for study enrollment. Pts with a confirmed pathological diagnosis of HEOC will be included in the step 1 of the trial which main inclusion criteria are the following: -availability of formalin-fixed, paraffin-embedded samples for the central testing of HRD status (performed by Myriad Mychoice CDx Plus assay) - suitability to receive CT + B. Only HRD+ pts responding to first line CT plus at least one cycle of B will be enrolled in the step 2 of the trial and will be treated with B 15 mg/kg every 3 weeks plus O 300 mg twice daily. Considering the PAOLA-1 median progression free survival (PFS) of 37.2 months (mo) in the B-O arm, with a sample size of 90 pts followed for 24 months and setting a one-side error of 5%, we will have a statistical power of 80% to demonstrate a PFS-24mo≥64% with an upper critical value of 61%. In order to have 90 patients eligible for the step 2 of the study, 190 pts are needed to be enrolled in the step 1 of the clinical study (as approximately 80% of pts with HEOC will respond to CT and out of these, 60% will be HRD+). The translational subproject 1 will consist of the analysis of circulating-tumor (ctDNA), using whole genome sequencing aiming - to correlate residual tumour after surgery and ctDNA levels - to anticipate the diagnosis of progression - to monitor the mutational status of HR-related genes and other genes such as Tp53BP1, POLQ, REV7 probably involved in PARPi resistance during the maintenance therapy. The translational subproject 2 will be developed to compare pts’ response to therapy with that of cancer cells, tested by organotypic model treated with the combination. These models will be generated using fresh tumor tissue and ascitic fluid for the isolation of the tumor cells and macroscopically healthy omentum for the isolation of the mesothelial cells and fibroblasts. Eight centers have been activated and other 6 are waiting for the activation with 19 patients registered and 3 screening failures. The enrollment is continuing, according to protocol timeline (12 months for enrollment, 6 months for surgery and CT and 24 months for maintenance treatment). Clinical trial information: NCT06121401 .