NEW YORK – Roche is gearing up to launch a fully automated version of its tissue-based comprehensive genomic profiling (CGP) sequencing kit that it claims will enable translational oncology researchers to achieve library preparation and target enrichment in about 24 hours with only 3.5 hours of hands-on time.
The forthcoming Avenio Tumor Tissue CGP Automated Kit will also feature a new pan-tumor homologous recombination deficiency signature score called HRDsig that is trained on Roche subsidiary Foundation Medicine's pan-tumor genomic database and surveys more than 100 unique genomic features.
Researchers from Roche and early-access user Circulogene presented early data on the planned product at a corporate-sponsored workshop and in several posters at the Association for Molecular Pathology annual meeting in Vancouver, British Columbia, last week.
At the workshop, Austen Cohen, international business leader for Roche Diagnostics, said that the automated assay will be available in February 2025.
The kit will follow on the heels of the Avenio Tumor Tissue CGP Kit V2, which launched with little fanfare in July of this year as an update to the first-generation kit introduced in 2021.
That update already features the HRDsig score, the interpretation of which is supported by Roche's Navify Mutation Profiler analysis software.
HRD is becoming increasingly important as a biomarker in several types of cancer, as the deficiency affects the ability of cells to repair double-strand breaks in DNA to ensure stability and viability. In particular, the use of an HRD score can potentially aid in determining eligibility for PARP inhibitor therapy in patients with breast or ovarian cancer.
Muriel De Vos, Roche's global medical affairs and strategic leader, noted during the workshop that HRDsig is a comprehensive scar-based signature that gives a functional pan-cancer HRD readout (HRD "scar" generally refers to a collection of genetic alterations or patterns in a cancer cell's genome that indicate HRD). Importantly, De Vos noted, HRDsig is intended to provide predictions "independent of genetic alterations, thus enabling the detection of non-genomic mechanisms of HRD." As such, she added, the signature captures a large fraction of biallelic BRCA cases as well as the subset of other homologous recombination repair (HRR) gene mutations and HRR wild-type cases likely to have true HRD.
Besides HRDsig, the current Avenio CGP V2 and the upcoming automated kit survey tumor tissue samples for single nucleotide variants, insertions and deletions, copy number alterations, and select gene rearrangements in 355 genes and also provide other genomic signatures such as microsatellite instability, tumor mutational burden, and genomic loss of heterozygosity.
The automated CGP workflow includes the Avenio kit, the Roche Avenio Edge liquid handling system, the Illumina NovaSeq 6000 for sequencing, and FoundationOne software for data analysis, all coordinated through Avenio Connect software.
Cohen noted that the Avenio Edge instrument is an open platform that can work with any NGS workflow but is "optimized to work spectacularly well for this new workflow." The kit reagents are pre-loaded in cartridges such that a user only needs to remove packaging and put it on the instrument, making it "different from any CGP workflows on the market," he said.
Roche noted that this workflow improves laboratory efficiency and minimizes human errors while reducing total turnaround time, with full reports available in less than five days.
This appears to be similar or better compared to other currently available commercial CGP kits or services. For instance, Illumina notes on its website that its TruSight Oncology Comprehensive kit, run locally in a laboratory like the Roche kit, has a sample-to-report turnaround time of four to five days.
Meanwhile, the Labcorp Tissue Complete service powered by the PGDx Elio assay advertises a turnaround time of six to 13 days, while the Guardant Health Guardant360 TissueNext service notes a turnaround time of under two weeks from sample receipt to results.
The major competing assay on the HRD front is Myriad Genetics' MyChoice HRD test, which is a US Food and Drug Administration-approved service to help identify patients with HRD and potentially aid in determining eligibility for PARP inhibitor therapy in patients with breast or ovarian cancer. Myriad advertises that it can return results after receiving a tumor specimen in "14 days or less."
Also, just last week, Myriad announced that Illumina is adding its genomic instability score (GIS) to Illumina's TruSight Oncology 500 v2 assay, which is in development and will be released globally in mid-2025. The updated assay will have faster turnaround time and reduced hands-on time compared to the earlier version, as well as sensitive variant calling and Myriad's GIS for determining HRD status, the companies noted.
At the AMP workshop, Eric Thompson, VP of translational research at liquid biopsy developer and early-access user Circulogene, noted that CGP is a "really complex workflow" that is time- and labor-intensive, involves large gene panels, and is constantly changing. He said that his company is using CGP primarily because it offers much greater insight than single-gene testing.
In an evaluation of the reproducibility of the Avenio automated CGP assay, Circulogene researchers found high agreement between their data and that produced at Roche, particularly for the genomic signature scores. He also reported that the time to load an assay run was on average less than one hour, even less than Roche is advertising.
"It works in our hands — full stop — with very high concordance and very robust results," he said. "Just in talking to my team … about bringing this assay into our lab, number one: It works. That's key. We can't compromise on quality when we're testing specimens from subjects. The automated kit is really walkaway."
One con of the system, Thompson noted, is that failed runs invalidate the reagents that are on deck on the platform, with the barcoded cartridges preventing future use. In addition, he noted, load-check errors take a long time to clear if an error is present.
In an email, Sunandini Chopra, a senior product manager at Roche, said that this is "an intentional feature to ensure that any errors observed have been corrected, which then requires the user to rerun the load check procedure from the start, making sure that all errors have been cleared. Designing the system in this way helps to ensure that failures later on in the process can be avoided and the run can proceed as expected."
Chopra said that other early-access users include laboratories in Belgium and Ireland, though Roche was not at liberty to identify them at this time. She also noted that other features of the automated kit include a 99.3 percent overall pass rate from FFPE tissue DNA extraction to sequencing results, compatibility with small-sized biopsy samples, very low contamination rates of 0.11 percent, and high analytical sensitivity in detecting small variants with a limit of detection of 1 percent to 3.1 percent — all data that the company made available in its AMP posters.
Roche stressed that both the Avenio CGP V2 kit and the automated kit are intended for research use only.
"In the short term, offering in-house CGP assays, software, and systems as research use only gives us the ability to keep improving and innovating our assay and help our customers be at the forefront of scientific advancements," Chopra said.
"It's Roche's intent to be in line with all regulatory bodies in markets of interest for our solutions," she added. "As the regulations [for lab-developed tests] and the implementation in different countries is still an evolving environment, we are carefully assessing when and how we would proceed [to IVD] for each of our solutions and would welcome partnerships."