TEST:

TruSight Oncology 500 HRD Assay

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.

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.

"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.

Sponsored by llumina

"We developed the Seraseq HRD reference materials to meet the needs of laboratories looking to analyze HRD in cancer patient samples. The HRD status of each material was evaluated using several assays using different measurement approaches. Although the materials showed similar trends and concordance among formats, there was variability in GIS across the methods tested."

"Illumina...and Myriad Genetics...announced the expansion of a strategic partnership to broaden access to and availability of oncology homologous recombination deficiency (HRD) testing in the United States. Under the agreement, Illumina TruSight™ Oncology 500 HRD (TSO 500 HRD), a research-use-only test, is now available in the US. The expanded partnership also establishes a unique companion diagnostic (CDx) alliance for the pharmaceutical industry, which will enable more clinical research for gene-based, targeted therapies."

The TSO 500 HRD assay demonstrated high analytical sensitivity and specificity in detecting BRCA variants and calculating a GIS for HRD status assessment in ovarian cancer samples. TSO 500 HRD enables high-resolution comprehensive genomic profiling alongside HRD assessment to maximize biomarker detection from limited amount of sample.

"Illumina...announced the upcoming presentation of multiple oncology research abstracts at this year’s European Society of Medical Oncology (ESMO) annual meeting, September 9–13 in Paris. The abstracts underscore the value of next-generation sequencing (NGS) and Illumina’s oncology assays for cancer research and patient care."

Conclusions The TSO 500 HRD assay demonstrated high analytical sensitivity and specificity in detecting BRCA variants and GIS status for HRD status assessment in ovarian cancer samples. TSO 500 HRD enables high resolution comprehensive genomic profiling alongside HRD assessment to maximize biomarker detection from limited amount of sample.

"Illumina, Inc...announced the launch of a research test, codeveloped with Merck (known as MSD outside the United States and Canada)...The Research Use Only TruSight Oncology 500 HRD test is a next-generation sequencing (NGS)–based assay that harnesses the power of Illumina NGS technology and validated HRD technology from Myriad Genetics (NASDAQ: MYGN), enabling labs to accurately detect genomic instability and analyze more than 500 genes simultaneously, including those relevant to HRD status."