HRD Harmonization Project
Homologous Recombination Deficiency Harmonization Project
Historically, cancer treatment involved and relied on chemotherapy, which attacks dividing cells throughout the body, including many cells that are not cancerous. In recent years, scientific innovation has allowed for the safe and effective use of targeted therapies, which can precisely attack cancer cells that have specific signals known as biomarkers, potentially providing more effective and safer treatments for patients. Since not all cancer cells have specific biomarkers targetable by current therapies, it is necessary to identify which patients have the biomarker and may benefit from specific targeted therapies. To help identify which patients have a specific biomarker, diagnostic developers have created tests, also known as assays.
Test developers have different approaches for how they identify a specific biomarker increasing variability across results from different tests. One such biomarker is homologous recombination deficiency (HRD), which is a characteristic of cells unable to properly repair DNA breaks and can be an indicator if certain therapies should be used. HRD testing is used to determine which patients may benefit from PARP inhibitors, a class of therapies that block the PARP enzyme from repairing damaged DNA, thereby preventing cancer cell division. A combination of factors is used to determine HR status, and different assays, or tests, use different approaches. This lack of harmonization can make it challenging for patients and providers to interpret the results of these tests.
To understand the variability in assays that test for HRD and identify potential solutions for harmonization, Friends convened a group of test developers, patient advocates, providers, and government officials. This collaborative effort aims to address concerns about the lack of consistency in identifying HRD, its prognostic value for predicting treatment efficacy, and its use as a predictive biomarker to determine how likely a patient is to respond to specific treatments. During the first phase of the project, the group conducted a landscape analysis of how HRD is used and defined to establish a baseline understanding of inconsistencies across tests and to propose common terminology.
Phase 2 of the project focuses on aligning assays used to measure HRD. As part of this effort, the group identified a set of biological samples for analysis. Each participating test developer will analyze these common samples using their respective HRD assays to report HRD status, indicating whether each sample is classified as HRD positive or HRD negative. The HR status will be compared across assays to understand the level of agreement among the assays. These results will be used to work towards defining where there are differences across assays and inform solutions to harmonize the results.
Friends’ HRD Harmonization Project will help determine the extent of agreement among assays that measure HRD and propose solutions to improve result accuracy in the future. If assay developers use agreed upon solutions in their assays, providers and patients will have more consistent results regardless of which assay is used to measure HRD. Without Friends coordination and support from collaborative sponsors, groups may never align on a solution to improve consistency across assays and interpreting results from assays would be more challenging for patients and providers.
Project Outcomes
2024
- Friends published a manuscript in JCO OA demonstrating variability in HRD results across assays, suggesting the need for consistent and aligned strategies in biomarker selection for clinical trials and clinical decision-making in oncology drug development.
- Friends hosted a public meeting sharing the full findings from the HRD Harmonization Project in February.
2023
- The Clinical Sample Findings that were presented at AACR Special Conference: Ovarian Cancer in October showed moderate variability in HRD status calls.
2022
- A manuscript describing opportunities and best practices to align the definition of HRD and the parameters that contribute to the determination of HRD status was published in The Oncologist.
- Friends launched the HRD Harmonization Project.
- Initial findings from the In Silico Findings from the project were presented at the AMP 2022 Annual Meeting and Expo in November demonstrating the inter-assay agreement on HRD status calls was variable.
2021
- The HRD working group convened and characterized current and future uses of HRD and HRD assays in oncology drug development.
Project Partners
Phase 1: Agilent Technologies, Inc., Ambry Genetics Corporation, Arizona State University, AstraZeneca, Bristol Myers Squibb, Caris Life Sciences, Inc., EMD Serono, Inc. (Merck KGaA), Foundation Medicine, Inc., GSK, Guardant Health, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Myriad Genetics, Inc., National Cancer Institute (NCI), Pfizer, Tempus AI, Inc., Thermo Fisher Scientific, the U.S. Food and Drug Administration (FDA), University of Alabama at Birmingham, and Heidelberg University.
Phase 2: ACT Genomics, Amoy Diagnostics Co. (AmoyDx), AstraZeneca, Bayer, Bionano Genomics, Inc., BostonGene Corporation, Bristol Myers Squibb, Burning Rock Biotech Limited, Diagnostic Laboratory Services, Inc., DNAnexus, Inc., EMD Serono, Inc., European Organisation for Research and Treatment of Cancer (EORTC), Foundation Medicine, Inc., Genentech, Inc., Guardant Health, Inc., Illumina, Inc., Invitae Corp, Labcorp Holdings Inc., MD Anderson Cancer Center, Merck & Co., Inc., Molecular Characterization Laboratory (MoCha) at Frederick National Laboratory, National Cancer Institute (NCI), Neogenomics Laboratories, Inc., PathAI, Pfizer, Pillar Biosciences Inc., SOPHiA GENETICS, Tempus AI, Inc., Thermo Fisher Scientific, the U.S. Food and Drug Administration (FDA), University of Alabama at Birmingham, and Heidelberg University.