TEST:

TruSight Oncology 500 HRD Assay

Age at diagnosis was not affected by both BRCA and wGI status. HRD Insight assay could accurately and robustly determine the HRD status of ovarian tissue samples, including those with low quality.

The FDA (US Food and Drug Administration) has approved olaparib as a front-line maintenance therapy in combination with bevacizumab for patients with newly diagnosed advanced ovarian, fallopian tube, or primary peritoneal cancer with HRD+ status. We have demonstrated that the TSO500-HRD assay can accurately determine HRD status in ovarian tumors.

The TruSight Oncology 500 comprehensive solid tumor next-generation sequencing panel with HRD assay demonstrated a high degree of sensitivity and specificity for deployment in a clinical setting.

"Subsequently, we assessed its efficacy in predicting response to the PARP inhibitor olaparib by comparing it with two other commercial assays: AmoyDx HRD by Amoy Diagnostics and the TruSight Oncology 500 HRD (TSO500-HRD) panel by Illumina NGS technology. While all three approaches successfully identified the most PARPi-sensitive CRC models, HRDirect demonstrated superior precision in distinguishing resistant models compared to AmoyDX and TSO500-HRD, which exhibited overlapping scores between sensitive and resistant cells. Furthermore, we propose integrating HRDirect scoring with ATM and RAD51C immunohistochemical analysis as part of our "composite biomarker approach" to enhance the identification of HRD tumors, with an immediate translational and clinical impact for CRC personalized treatment."

Conclusion/Implications Early-stage OCCC tumors showed high occurence of FT associated with lower immune scores and recurrence rate. Functional elucidation of novel FT is warranted.

Compared with the 3 kits, our assay showed a concordance rate of 94.6%, positive percent agreement and negative percent agreement of 96.4% and 92.9% respectively. Conclusions HRD status could be accurately and reliably determined by our HRD Insight assay to help physicians select approved PARPi for OC patients.

Different molecular assays had high accuracy for identifying deleterious BRCA1/2 alterations while exhibited a few inconsistent in identifying HRD status.

63% of patients received platinum-containing first line therapy (1L-platin) and 37% gemcitabine-based regimens (1L-gem)... These preliminary results underscore the rarity of pathogenic BRCA variants in PDAC, along with a lower GIS. Few tumours were classified as HRD-positive per existing criteria. Instead, the identification of P/LP variants in other HRR-genes that are associated with a lower GIS point towards the existence of BRCA-independent mechanisms in pancreatic cancer HRD and argues for refined HRD-criteria for this entity.

Our data suggest the feasibility of commercial testing for assessing HRD status, with a good concordance with the reference method and association with clinical outcome.

This study demonstrates the utility of CGP and HRD testing in identifying multiple molecular alterations in FFPE tissue samples with high sensitivity and specificity. Pre-analytical variables directly impact data generation. BRCA1/RAD51C promoter methylation showed to be a potential biomarker for selecting metastatic TNBC patients for PARP inhibitor therapies.

Assays for GI assessment not only show a high concordance with each other but also in correlation with Myriad myChoice. Thus, almost all of the assays included here can be used effectively to assess HRD-associated GI in the clinical setting. This is important as PARPi treatment on the basis of these tests is compliant with European Medicines Agency approvals, which are methodologically not test-bound.

Comparison between the Illumina and Myriad assays showed that overall HRD status, the individual components of BRCA analysis, and HRD GIS detection results were highly concordant (>93%), suggesting the TSO 500 HRD assay will approach the analytical accuracy of the FDA-approved Myriad assay.