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Spanish Cancer Institute Using Sysmex Inostics, Merck Serono Blood Dx to Study mCRC Personalized Rx


NEW YORK (GenomeWeb) – Vall d'Hebron's Institute of Oncology in Barcelona, Spain will be the first liquid biopsy testing center that will use Sysmex Inostics' OncoBEAM blood test as part of its research on RAS biomarkers in the context of personalizing treatments for metastatic colorectal cancer patients.

"This marks an important milestone in Sysmex Inostics' collaboration with … Merck Serono," the partners said in a statement announcing the adoption of the test by Vall D'Hebron.

Merck Serono, the pharma business under Merck KGaA, inked a deal with Sysmex Inostics for the development and commercialization of a blood-based RAS biomarker testing kit for metastatic colorectal cancer patients last year at the American Society of Clinical Oncology's annual meeting. The test, called RAS OncoBEAM, gauges mutations in RAS genes in ctDNA and uses Sysmex Inostics' emulsion-based digital PCR technology, called BEAMing, which stands for beads, emulsions, amplification, and magnetics. 

Treatment guidelines currently recommend testing for mutations in RAS genes – KRAS and NRAS – to inform treatment for colorectal cancer patients who are considering treatment with anti-EGFR monoclonal antibodies, such as Erbitux (cetuximab) and Vectibix (panitumumab). Erbitux is marketed by Bristol-Myers Squibb in the US and in Canada, and outside these territories by Merck KGaA. The FDA first updated the labels of these drugs in 2009 to note that patients with mutations in the KRAS gene were unlikely to respond to the therapies.

However, studies since them have shown that drug response is affected by additional mutations in the RAS pathway. Sysmex Inostics estimates that as many as 50 percent of metastatic colorectal cancer patients have mutations in RAS genes, such as NRAS and KRAS. And the National Comprehensive Cancer Network last year updated guidelines to recommend that healthcare providers test colorectal cancer patients for KRAS and NRAS mutations to inform treatment strategies.

Currently, there is no FDA-approved companion diagnostic for Erbitux and Vectibix that gauges a broad panel of RAS mutations. However, there are agency-approved tests that gauge KRAS mutations (Qiagen's Therascreen RGQ PCR Kit) and EGFR expression (Dako's EGFR PharmDx Kit), and these are tissue-based tests.

Sysmex Inostics' OncoBEAM blood test may be particularly useful in situations where a tissue biopsy sample is not available for a patient, or the patient cannot undergo an invasive biopsy. The test might also be useful in monitoring disease progression, according to the firm.

According to a spokesperson, the benefits of a liquid biopsy test is one reason Vall d'Hebron will use OncoBEAM to test metastatic colorectal cancer patients' blood samples for RAS markers in a research setting first. The institute will likely provide testing in the broader medical care setting once the test achieves the necessary marketing certifications.

In the research setting, results from the OncoBEAM test will inform Vall d'Hebron's investigations on effective therapies directed at tumors characterized by mutations in RAS oncogenes. "The ability to test for these mutations at Vall d'Hebron rapidly from a simple blood draw will be paramount in improving the standard of care for patients," a Merck Serono spokesperson told GenomeWeb. "The convenience of the liquid biopsy RAS biomarker test enables real-time monitoring of RAS mutation status in mCRC."

Sysmex Inostics highlighted that the test only requires a blood sample, and the firm is targeting a turnaround time of two to three days.

Sysmex Inostics and Merck Serono expect the ctDNA test to achieve CE self certification in the third or fourth quarter of this year. According to the spokesperson, the test is already developed and available for research use, as with the Vall d'Hebron effort. "Once the liquid biopsy RAS biomarker test becomes widely available, it will be used at the discretion of the individual clinician," the spokesperson said.

After Sysmex Inostics is able to market the test for clinical use with CE marking, healthcare providers will want to know how accurate the liquid biopsy test is compared to tissue-based tests. Vall d'Hebron is conducting a concordance study in this regard, and Sysmex Inostics is hoping to present the data at an upcoming medical meeting later this year.

In metastatic colorectal cancer, "there are not any existing studies that compare these two testing procedures," said the Merck Serono spokesperson, highlighting that the concordance study at Vall d'Hebron will yield data in this regard. "In addition, we are currently running a number of concordance studies in various countries."

Following Vall d'Hebron's implementation of the OncoBEAM RAS test, Sysmex Inostics is hoping to open other testing centers throughout the year in Australia, France, Germany, Italy, and the UK. Next year, the company hopes to expand test access globally, in Latin America and Asia, for example.

For the time being, the collaboration between Merck Serono and Sysmex Inostics is restricted to outside the US.

Although the NCCN guidelines recommend RAS testing for metastatic colorectal cancer patients to inform treatment strategies, such testing is not yet an FDA-issued regulatory requirement in drug labeling. "Therefore our focus is currently supporting the opening of additional testing centers and supporting wider access to the liquid biopsy test in ex-US countries," said the spokesperson, highlighting that in the US the OncoBEAM tests are available as lab-developed tests through the CLIA certified Sysmex laboratory.

Sysmex offers OncoBEAM testing for biomarkers associated with a number of different tumor types, and the technology has attracted the attention of other drug developers exploring non-invasive methods of gauging whether cancer patients are likely to respond to certain drugs. For example, Clovis Oncology's Chris Karlovich recently said at a conference that the company is comparing the performance of Sysmex Inostics' BEAMing assay service to that of Qiagen's TheraScreen EGFR PCR test in a subset of patients enrolled in a clinical trial for rociletinib, a non-small cell lung cancer drug for patients with EGFR mutations. 

Karlovic presented initial data comparing BEAMing plasma testing and corresponding tissue testing in 119 lung cancer patients positive for activating EGFR mutations. Of these, 102 were positive for mutations in plasma, yielding a positive agreement of 86 percent with tissue testing. However, 23 patients positive for mutations by tissue testing were negative in plasma, and 14 patients negative in tissue were positive in plasma. Secondary testing showed that the negative tissue tests were actually true positives. BEAMing aslo identified 101 patients positive for T790M mutations, matching the number of patients identified via tissue testing when inadequate tissue specimens were factored in to the analysis.