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Expansion of Liquid Biopsy Test Sites Planned by Merck KGaA, Sysmex


NEW YORK (GenomeWeb) – Merck KGaA and Sysmex Inostics are planning to set up additional test sites for the OncoBEAM RAS CRC liquid biopsy diagnostic in Asia and South America.

The two firms began developing the RAS mutation panel following a 2014 deal. The test is based on Sysmex's emulsion-based digital PCR technology, called BEAMing, which stands for beads, emulsions, amplification, and magnetics.

Merck KGaA and Sysmex announced last week that they had garnered a CE Mark for the test. They also said they will now market the test in Europe, Asia, and Australia as a tool oncologists can use to determine which metastatic colorectal cancer patients have RAS mutations and would likely benefit from EGFR inhibitors, such as Erbitux (cetuximab). The drug is marketed by Lilly in the US and Canada, and by Merck KGaA outside these territories.

In line with these expanded marketing efforts, the companies are also planning to set up additional test sites for OncoBEAM RAS CRC in Argentina, Brazil, Malaysia, Indonesia, Vietnam, and India, an external spokesperson for Merck KGaA told GenomeWeb.

The Vall d'Hebron Institute of Oncology in Barcelona, Spain last year became the first testing center for the blood test. Since then, test centers have been set up in Spain, France, Germany, Italy, UK, Slovakia, Australia, and Japan.

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 and Vectibix (panitumumab). The US Food and Drug Administration approved labels of these drugs that indicate them only for patients with wild-type KRAS status as determined by a test that is also approved by the agency. The drug labels also limit their administration in patients with RAS-mutant metastatic colorectal cancer.

Several years ago, the FDA approved tissue-based companion diagnostics that gauge patients' KRAS status in order to determine if they can receive these drugs. But the FDA hasn't approved companion diagnostics for Erbitux and Vectibix that gauge a broad panel of RAS mutations in tissue or blood.OncoBEAM RAS CRC analyzes blood samples for 34 mutations within Exon 2, 3, and 4 of the KRAS and NRAS genes.

The spokesperson noted that since Merck KGaA doesn't market Erbitux in US, it doesn't have plans to launch the OncoBEAM CRC test kit in this market. However, under a global deal inked last year between Sysmex and Laboratory Corporation of America, the two firms will be able to offer testing as a lab service at a number of US centers, according to the spokesperson.

"Currently there are no plans to launch an FDA-cleared test kit, but … using CLIA lab services with LabCorp will make the technology available in that market," the spokesperson added.

Meanwhile, there are a number of concordance studies underway comparing the liquid biopsy test with standard tissue-based diagnostics. Several of these studies will be presented at upcoming conferences, including the American Society of Clinical Oncology's annual meeting.

In order to garner a CE Mark for the test, Sysmex internally performed a concordance study with 238 samples, according to the spokesperson. In this study, overall concordance of the liquid biopsy RAS test with tissue testing was 93.7 percent.

Wolff Schmiegel, professor of medicine at Ruhr-Universität Bochum, has assessed OncoBEAM RAS CRC in more than 100 metastatic colorectal cancer patients and has found it has more than 90 percent concordance when matched tissue samples are analyzed by next-generation sequencing, pyro-sequencing, and Sanger sequencing. The specificity of OncoBEAM was 94.5 percent and sensitivity was 93 percent.

Schmiegel noted that researchers are currently evaluating the reasons why the liquid biopsy and tissue-based test results were discordant in a small percentage of samples. However, based on the data so far, he believes the OncoBEAM RAS test will prove to be a "realistic and reliable" tool.

He noted that OncoBEAM may be useful as an adjunct to tissue-based testing to predict whether patients will respond to anti-EGFR monoclonal antibodies. OncoBEAM can also come in handy when patients' cancers have progressed to a point where they cannot provide tissue or in situations where the available tissue no longer reflects the current disease state.  

OncoBEAM, importantly, "provides an overall impression" of the inter- and intra-tumor heterogeneity of a person's cancer, by revealing RAS mutations from primary or metastatic lesions, Schmiegel said. Using the test, doctors can monitor whether RAS wild-type is still expressed by tumor clones or whether a patient is acquiring mutations in RAS, which will make them resistant to treatment.

"Giving the antibody is successful in the beginning, but after a couple of weeks, a month, the tumor evolves to become resistant to the therapy," Schmiegel said. "As soon as we detect not only wild-type RAS but mutated RAS species, we already know an antibody resistance will result very soon. So, we can stop an ineffective therapy earlier than we can by waiting for progress reflected by imaging procedures or by other biochemical assessments."

He estimated that OncoBEAM can detect that metastatic colorectal cancer patients are becoming treatment resistant four to six weeks earlier than traditional testing modalities.

Next, in FIRE-4 — a prospective study enrolling approximately 600 colorectal cancer patients and led by Volker Heinemann at the University of Munich — Schmiegel and his colleagues will be further exploring the OncoBEAM RAS CRC test's ability to monitor for therapy resistance.