Abstract 1492: Clinical validation on the PAOLA-1/ENGOT-ov25 cohort of HRD calculation performed with the OncoDEEP® kit comprehensive genomic panel

Abstract

Abstract Introduction: Homologous Recombination Repair (HRR) pathway repairs DNA double-strand breaks. Loss of HRR capability is known to lead to genomic instability resulting in a phenotype called Homologous Recombination Deficiency (HRD). The utility of HRD biomarker in cancer treatment lies in its ability to predict response to specific types of therapy such as platinum-based chemotherapy and PARP inhibitors (PARPi). HRD tests evaluating scores of allelic imbalances, such as genomic scar (GS) or loss of heterozygosity (LOH), have been shown to identify a subgroup of BRCA wild-type (wt) tumors showing a HRD phenotype. Currently, HRD status is being used as a biomarker in cancer profiling, helping clinicians determine the best treatment option for their patients. In this perspective, OncoDNA® has developed a pan-cancer tumor profiling solution, the OncoDEEP® kit, facilitating the genomic analysis of both tumor DNA and RNA, and supported with Bio-IT analysis and clinical reporting. This end-to-end solution screens for a very wide range of cancer biomarkers and genomic signatures such as HRD. Hence, the OncoDEEP® kit can aid in reducing the costs of testing and deliver faster results for the selection of appropriate cancer treatment. Methods: OncoDEEP® kit, based on Twist technology, was performed at OncoDNA laboratory facilities on 246 extracted DNA from FFPE ovarian carcinoma of the PAOLA-1/ENGOT-ov25 cohort. Those samples were previously characterized with Myriad Mychoice DX and obtained at Arcagy Gineco®. Sequencing was performed on Illumina Novaseq X. All 638 genes on OncoDEEP® panel, inclusive of BRCA1/2 and other HRR genes, were analyzed via OncoDNA proprietary bioIT pipeline and GS was calculated using Loss of Heterozygosity (LOH), Allelic Disparity on Telomere (ADT) and Large-scale Rearrangements (LR), with a positive threshold of 37. Afterwards, results were matched with PFS and treatment. Results: HRD analysis of OncoDEEP® showed a high correlation with Myriad MyChoice DX, with an overall concordance of 85 %. In addition, OncoDEEP showed to be highly predictive (p-value≤0.001) of tumor response to olaparib+bevacizumab. Tumors harboring a positive HRD phenotype and treated with olaparib+bevacizumab exhibited a median PFS of 36.4 months, while median PFS of placebo-treated tumors was 18.75 months. Finally, OncoDEEP analysis presented a lower failure rate (0.8%) compared to Myriad MyChoice Dx (6.5%). Conclusion: OncoDEEP® kit is an end-to-end solution allowing the detection of variants in 638 genes and the calculation of genomic signatures such as TMB, MSI and HRD. OncoDEEP® HRD analysis showed to be highly predictive of tumor response treated by olaparib+bevacizumab and is therefore applicable to the identification of ovarian cancer patients eligible to PARPi therapy in oncology routine. Citation Format: Marcel Trautmann, Simon Lefèvre, Sébastien Sauvage, Jessie Hong, Maxime Liénard, Karim Ashour Garrido, Jean-François Vanbellinghen, Rapahël Léonard. Clinical validation on the PAOLA-1/ENGOT-ov25 cohort of HRD calculation performed with the OncoDEEP® kit comprehensive genomic panel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1492.