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Roche Previews RUO CAPP-Seq Liquid Biopsy Assays at AMP Meeting, Shares Early User Data

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CHARLOTTE, North Carolina (GenomeWeb) – Roche this week previewed its new set of sequencing-based liquid biopsy assays for cancer research, hosting an early-access tester of the products who shared some of her data at the Association for Molecular Pathology meeting held here.

Shelly Gunn, chief medical officer of contract diagnostics organization ResearchDx (and medical director of its subsidiary Pacific Diagnostics Clinical Laboratory) introduced the new assays, which Roche has named "Avenio ctDNA kits," at a workshop on Wednesday.

She also shared data from reproducibility experiments conducted by ResearchDx and two other early-access users.

The new assays — one targeting 17 genes and one targeting 77 genes — are based on the CAPP-Seq technology developed by Stanford University's Max Diehn and Ash Alizadeh, which Roche acquired when it bought Diehn and Alizadeh's newly-formed company CAPP Medical in mid-2015.

Diehn's and Alizadeh's groups first published on CAPP-Seq — which stands for Cancer Personalized Profiling by deep Sequencing — in Nature Medicine in 2014.

The method involves identifying highly mutated genomic regions for specific cancer types based on existing data, capturing those regions in patient blood samples, and sequencing them with high coverage.

In the 2014 Nature Medicine study, the researchers assessed their CAPP-seq assay on 40 samples from 13 patients with non-small cell lung cancer, demonstrating that they could detect mutations down to a 0.02 percent frequency.

More recently, the Stanford investigators have described an improved version of CAPP-Seq that incorporates error correction to be able to detect mutations present at frequencies of 0.004 percent, by incorporating molecular barcoding and a statistical method they call integrated digital error suppression (iDES).

Roche, meanwhile, has already become a player in the liquid biopsy space, but mostly in the context of single-gene PCR-based assays. This summer the company successfully brought the first ever liquid biopsy assay through the US Food and Drug Administration, its cobas EGFR Mutation Test v2.

That assay, which is PCR-based, was approved initially as companion diagnostic to identify patients with EGRF mutations that confer eligibility for treatment with Genentech's cancer drug Tarceva, and is now also indicated to identify additional EGFR mutations that predict patients' response to AstraZeneca's second-generation inhibitor Tagrisso (osimertinib).

The company's new CAPP-Seq ctDNA assays are currently intended only for research, Gunn stressed at the meeting. However, their great promise, as she highlighted, will probably be in testing cancer patients clinically to help guide treatment decision-making and monitor the progression of disease.

Clinical labs can, and do, validate tests and offer them clinically under CLIA and state-based agencies, in which they use research-use-only, or RUO tools. However, manufacturers are cautious to specify that products developed as RUOs should not be used for patient testing.

During the AMP meeting, Gunn described some intra- and inter-laboratory reproducibility experiments that ResearchDx performed with two other early evaluators of the new Avenio kits.

The three labs tested a set of 42 control and contrived samples that were either based on particular SNPs, or fusions at varying concentrations.

One of the two Avenio kits is designed to interrogate just 17 genes with a focus on targets with more direct relevance to approved therapies, while the other targets 77 genes including genomic features that can help recruit patients to clinical trials or provide other more investigatory information.

The kits have accompanying bioinformatic support, and are designed to be performed with a five-day turnaround time.

According to Gunn, all three early-access labs had almost perfect concordance in detecting SNPs down to 0.25 percent allele frequency, and fusions down to 1 percent frequency, when they evaluated the 42 test samples.

In studies published on CAPP-Seq by its academic inventors, researchers have claimed much lower detection limits down to below 0.01 percent. Gunn also highlighted specifically in her presentation that the hope is that that level of detection can be demonstrated not only in a research setting, but also clinically.

A Roche spokesperson told GenomeWeb in an email that that the company's plans are currently limited to providing the new panels as RUO kits. She did not provide any detail on when they will be widely or fully available to customers.

Roche is not alone in moving NGS-based liquid biopsy assays into the market. Thermo Fisher Scientific also announced at AMP that it has two ctDNA sequencing assays that will be coming out in the next few weeks—one for breast cancer and one for colon cancer.

These join a panel for non-small cell lung cancer that the company launched earlier this year.

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