Hrd-positive
Those projects and a handful of others also announced at the conference share a common goal of expanding Illumina’s genomic sequencing offerings for cancer diagnosis, a mission spearheaded by the company’s dogged pursuit to acquire former spinout Grail. At the time, Illumina said it would work with Myriad to create a kit-based version of the m圜hoice CDx for international distribution and with Merck to study that kit-collaborations that have evidently both proven successful throughout the ensuing months. This partnership builds on collaborations with Merck and Myriad that Illumina announced at the annual J.P. RELATED: Illumina completes Grail acquisition, regulators be damned Illumina's research use only HRD test, meanwhile, will be added to the TruSight Oncology 500 menu and will be available in countries outside of the U.S. “By leveraging our comprehensive genomic profiling family of products, TruSight Oncology, and the gold standard m圜hoice HRD technology, Illumina aims to offer the best-in-class HRD assay that is broadly accessible,” said Joydeep Goswami, Illumina’s chief strategy and corporate development officer. In addition, the new Lynparza test is developed specifically for use in the U.K. Integrating Illumina’s sequencing technology will offer more comprehensive tumor profiling capabilities to the HRD-detecting test, according to the companies. The m圜hoice CDx test has already been approved on its own as a companion diagnostic for use with Merck and AstraZeneca’s PARP inhibitor Lynparza (olaparib).
The companion diagnostic will combine Illumina’s TruSight Oncology 500 assay, a next-generation sequencing test that analyzes more than 500 cancer-related genes, with Myriad’s m圜hoice CDx, which detects variants in the BRCA1 and BRCA2 genes to determine HRD status. RELATED: JPM: Illumina inks multiple cancer diagnostic partnerships to complement upcoming Grail acquisition Here, we discuss the premise of HRD testing in HGSOC, current methodologies for HRD identification and their performance in the clinic, highlight upcoming strategies, and discuss the challenges faced in moving this field forward.Because an estimated 50% of all women diagnosed with late-stage ovarian cancer have HRD-positive tumors, regular HRD testing could lead to major improvements in the overall outcomes of ovarian cancer patients-which is where Illumina, Merck and Myriad come in. It is thus critical that HRD testing is optimized to address the controversies of diverse HRD testing methodology, appropriate thresholds for HRD identification, and relevant timepoints for HRD testing, in order to realize the potential for PARPis to maximally benefit patients with HGSOC. In practice, this means that restoration of HRR through mechanisms of platinum and PARPi resistance are not adequately represented by genomic scar assays, and contribute toward discordance with clinical PARPi response, or lack-thereof. Yet despite the rapid maturation of this field, tumoral HRD status has been recognized to be dynamic over time and with treatment pressure. At present, clinical-grade assays such as m圜hoice CDx and FoundationOne CDx are approved companion diagnostics which can identify patients with HRD-positive HGSOC by diagnosing a ‘genomic scar’ reflecting underlying genomic instability. Recent data have drawn attention to the assessment of homologous recombination DNA repair (HRR) as a prognostic and predictive biomarker in HGSOC, leading to increasing debate on the optimal means of defining and evaluating HRD, both genotypically and phenotypically. Poly(ADP-ribose) polymerase inhibitors (PARPis), developed based on the rationale of synthetic lethality that predicates antitumor efficacy in tumors harboring underlying HRD, now represents an important class of therapy for HGSOC. The recognition of homologous recombination deficiency (HRD) as a frequent feature of high-grade serous ovarian cancer (HGSOC) has transformed treatment paradigms.