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New Oncology Seeks Local Adoption of Liquid Biopsy Test; Publishes Case Study

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NEW YORK (GenomeWeb) – After launching its first blood-based cancer sequencing test last month, German firm New Oncology is hoping that increasing awareness among oncologists about the benefits of liquid biopsy will spur adoption of the assay, called NEOliquid.

Jutta Fritz, New Oncology's chief business officer, and Johannes Heckman, the company's chief scientific officer, told GenomeWeb this week that the test is the first of its kind to be offered alongside tumor tissue sequencing by a Europe-based laboratory.

Though Fritz declined to provide details on the company's early test volume or how many customers it expects in the near future, she said that New Oncology believes that its liquid biopsy operations will increase rapidly based on growing awareness of the benefit it can offer to cancer patients over traditional tissue biopsy analysis.

Although the company has not yet publicly released any of its validation data, New Oncology researchers, along with collaborators from Switzerland's Luzerner Kantonsspital, this month published a letter to the editor of the Journal of Thoracic Oncology making a case for the clinical efficacy and utility of NEOliquid in a single case study.

In the case study, NEOliquid discovered a crucial mutation in a 53-year-old patient with metastatic lung adenocarcinoma who had previously been extensively treated with EGFR inhibitors.

The patient, according to the researchers, was one of the first tested as part of an IRB-approved research collaboration begun this year between the Swiss hospital and New Oncology.

While conventional tissue testing failed to discover any genomic alterations with relevance to future treatment for the patient in question, NEOliquid found an EGFR T790M resistance mutation in the man's blood sample.

As a result, the patient was put, under a compassionate use agreement, on an experimental third-generation EGFR-inhibitor, AZD9291, now AstraZeneca's Tagrisso (osimertinib). On this new therapy, his disease rapidly responded, according to the researchers.

When the company continued to serially test the patient every two weeks, NEOliquid showed a gradual decrease of the T790M resistance mutation in his blood over time, supporting the observed efficacy of the drug. As of today, the letter authors wrote, clinicians have observed "no clinical, radiological, or genomic evidence of tumor progression," and the patient remains well and on treatment.

Tagrisso was approved by the US Food and Drug Administration for patients with EGFR T790M mutation-positive metastatic non-small cell lung cancer this November. As a companion diagnostic, the FDA also approved Roche's Cobas EGFR Mutation Test v2, which runs on the Cobas 4800 qPCR system and detects EGFR mutations in tumor tissue DNA.

Currently, there are no liquid biopsy tests that have been officially approved as companion diagnostics to guide therapy with EGFR inhibitors or other lung cancer therapies.

Roche does offer a CE marked version of the EGFR Mutation Test v2 that is appropriate for either plasma or tumor tissue samples, although the FDA has not recognized that test as an official companion diagnostic to Tagrisso or any other EGFR-inhibitors.

However, the oncology field is increasingly warming to the view that these tests have independent value that tissue biopsy cannot provide, for example for patients with late-stage, advanced disease, who, as in the New Oncology case study, cannot be re-biopsied to detect newly acquired resistance mutations.

In that vein, some drugmakers have said that they are exploring the use of liquid biopsy companion tests to pick out best responders to their drugs. For example, AstraZeneca has made public one deal with Qiagen and another with Roche to advance liquid biopsy-based companion diagnostics for Iressa (gefitinib) and Tagrisso (osimertinib) respectively.

Roche's assay, as well as Sysmex Inostics' BEAMing technology and Boreal Genomics' OnTarget platform, are all also being evaluated by Clovis Oncology as tests to identify candidates for its investigational EGFR inhibitor rociletinib.

"I think the knowledge is rising quite rapidly," Fritz said. "People are aware of what targeted therapies can do and how solid molecular diagnosis is the basis for that."

Meanwhile, she said, cases like the one New Oncology published in its letter offer a very clear example of the potential limitations of tissue testing and the added value of liquid biopsy.

"If you can't get a solid tissue-based diagnosis you have to look further, and sometimes it's just impossible to get tissue, so the logical next step is a liquid biopsy. I think oncologists, at least in my experience, are understanding this very well," she said.

Unlike simpler amplification-based EGFR assays like those from Roche, Qiagen, and others, New Oncology's NEOliquid is a broad sequencing-based test that offers the opportunity to simultaneously detect not only EGFR mutations, but a range of other cancer genome alterations that have relevance for guiding therapy in lung cancer.

Heckman told GenomeWeb that New Oncology's technology is hybrid-capture based, which allows for the identification of not only point mutations, but also insertions, deletions and gene fusions in circulating cell-free DNA. The company says its approach is sensitive down to an allele frequency of 0.1 percent.

According to Fritz, New Oncology believes it is the first company based in Europe to offer such comprehensive analysis of both tissue and blood. However, outside Europe, the firm has several competitors in broad sequencing-based liquid biopsy testing.

One, Guardant Health, said this week that it had solidified a partnership to distribute its Guardant360 test in some European and South American countries, beginning first with Spain, and that it had received the CE mark for the sample collection portion of its test, allowing it to distribute the kit in European countries and run the assay from its CLIA-certified, CAP-accredited Redwood City, California laboratory.

Another US-based liquid biopsy sequencing company, Resolution Biosciences, has said it plans to address the European market by taking a disseminated, kit-based approach, initially with a small group of early, research use testers.

Fritz said that New Oncology is currently married to a centralized testing model, where all its services are performed in house in its Cologne-based lab, rather than adapting to a format that could be sold to and operated by other labs, although the firm is open minded to potential shifts in strategy.

Overall, Fritz argued that other companies may offer valid and useful tests similar to New Oncology's, but that its strong network in Germany and extensive relationships with opinion leaders in other relevant European markets are an advantage.

"I think our strong point is really that we work very, very closely with clinicians," she said. "They can call us any time, an offer that is already used quite heavily [with our tissue-based test.]"

Fritz and Heckman did not provide any details on New Oncology's liquid biopsy test volume in its local markets so far.

Fritz did say that the list price of NEOliquid for commercial customers is €3,700 (about $4,000). "At the moment, [New Oncology's testing] is a self-pay resource and the costs are not reimbursed by state or private health insurance," Fritz said in an email. However, the company supports patients in their claims for reimbursement, she said.

According to the letter published by New Oncology and the Luzerner Kantonsspital researchers, the single case study comes out of a research collaboration between the hospital and New Oncology, implying that additional patients from the Swiss institute may be tested by the company.

Fritz declined to discuss details of the collaboration.

The company plans to release data on the validation of its test in abstracts at upcoming scientific meetings next year, she said.