Background: SOPHiA DDM Dx HRD Solution (SOPHiA GENETICS, SA) combines analysis of genomic instability with mutational status of HRR genes, including BRCA1/2, generated through a single genomic workflow in order to to predict Homologous Recombination Deficiency (HRD) status in ovarian cancer (OvCa) samples. Previous evaluation of SOPHiA DDM Dx HRD Solution demonstrated its results to be highly concordant with a reference HRD method. As part of the ENGOT HRD initiative, we present updated clinical relevance results of SOPHiA DDM Dx HRD Solution. Methods: GINECO/ENGOT-Ov25 PAOLA-1 trial randomized (2:1) 804 patients (pts) to receive after the end of first-line platinum-based chemotherapy either maintenance olaparib+bevacizumab or placebo+bevacizumab for up to 2 years. DNA from a sub-cohort of 384 formalin-fixed paraffin-embedded (FFPE) OvCa pts samples included in the PAOLA-1 clinical trial were analyzed using SOPHiA DDM Dx HRD Solution(*). We combined SOPHiA DDM Dx HRD Solution genomic instability score, with BRCA mutational status obtained from a Clinical Decision Support module, and clinical interpretation of Variants of Unknown Significance to establish the pts HRD status and investigated differences in progression-free survival (PFS) in the olaparib+bevacizumab and placebo+bevacizumab arms between pts with HRD positive or HRD negative test. Results: We determined the HRD status of 98.4% of pts using SOPHiA DDM Dx HRD Solution. The median PFS time for pts with HRD positive tumors was 35.7 months longer in the olaparib+bevacizumab arm than in the placebo+bevacizumab arm (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.25-0.51, p< 0.001), confirming the findings of our previous interim analysis. No significant difference in PFS was observed between treatment arms in pts with HRD negative test (HR, 1.02; 95% CI, 0.71-1.48; p= 0.90). Conclusions: These clinical relevance results from the SOPHiA DDM Dx HRD Solution evaluation on the PAOLA-1 samples further support the value of combining low-pass whole genome and targeted sequencing in a unique workflow for reliable and cost-effective HRD testing and future patient stratification. (*) Comparison data generated using the CE-IVD pipeline with Clinical Decision Support module for BRCA status only available in EU, Switzerland, UK.