NEW YORK (GenomeWeb) – Molecular diagnostics firm MetaStat is on track to launch its MetaSite Breast and MenaCalc Breast cancer tests next year as prognostic tools for ER-positive, HER2-negative patients.
The Boston-based firm announced last week that it had completed analytical validation of MetaSite Breast, an immunohistochemistry test that quantifies active sites, or windows, for tumor metastases. The study showed greater than 97 percent reproducibility for MetaSite in assessing samples from invasive breast cancer patients.
"This is a critical milestone for us," Mark Gustavson, VP of diagnostics, told GenomeWeb. Typically, gold standard pathologists' consensus assessments achieve between 75 percent to 80 percent reproducibility, he estimated. "In the clinical setting, we need to develop a more objective approach other than pathologists' count," Gustavson said.
The analytical validation puts the firm on track to achieve lab certification in Massachusetts and under the Clinical Laboratory Improvement Amendments. CLIA certification will be important for the commercialization of MetaSite and MenaCalc, since the company wants to launch them as lab-developed tests.
The IHC-based MetaSite stains formalin-fixed paraffin-embedded tissue for three-cell clusters comprising a Mena protein-expressing tumor cell, an endothelial cell, and a macrophage. These clusters, called the Tumor Microenvironment of Metastasis (TMEM), create a window for cancer cells to escape into the bloodstream. Using samples from ER-positive, HER2-negative breast cancer patients, researchers have published studies showing that MetaSite's TMEM score can predict the risk of distant metastases.
MenaCalc Breast assesses the ratio of Mena protein isoforms MenaINV and Mena11A. Studies have shown that increased expression of MenaINV is associated with breast cancer aggressiveness and higher risk of metastases.
MetaStat executives claim based on research data that the Mena protein is a prognostic factor for HER2-positive and triple-negative breast cancers, and also in lung, prostate, and colon cancer. Earlier this year, MetaStat presented data from a study involving 200 non-small cell lung cancer patients, which showed that MenaCalc scores were significantly higher in patients with squamous cell carcinoma, denoting worst five-year survival. MenaCalc scores were also two-fold higher in patients with metastatic disease.
But in the near term, the company plans to commercialize both MetaSite and MenaCalc in the ER-positive, HER2-negative breast cancer subtype, accounting for up to 60 percent of cases. With these two tests, MetaStat aims to quantify two mechanistic aspects of breast cancer metastases: how many multi-cellular window structures does the tumor have and the level of tumor invasiveness based Mena protein expression.
"So, if you have very invasive tumor cells and a lot of these windows of metastases in your tumor, you have a very great likelihood of developing metastatic disease," Gustavson said. "This, at the end of the day, is what we're all looking to predict. That's what patients ultimately succumb to."
Before launching these two diagnostics next year, MetaStat plans to conduct three additional studies to further establish their clinical validity and utility. In the first of these trials, called the Kaiser Cohort Validation Study, MetaStat will use deidentified samples from 500 patients with and without metastatic breast cancer from Kaiser Foundation Hospitals. Researchers hope to replicate the clinical validity of MetaSite established in earlier investigations and also further develop a combined algorithm based on the MetaSite and MenaCalc diagnostic tests.
MetaStat will also differentiate the scientific basis of its tests from gene-expression panels. "Based on all the preclinical work, the studies on MenaCalc, and what we understand of the biology, we have evidence to support that taking these two tests will have greater prognostic and predictive value that the individual tests," Gustavson noted.
In a second study, MetaStat hopes to show that these tests alone or in combination can predict overall survival and recurrence-free survival in different breast cancer subtypes, and compare the performance of the diagnostics to Genomic Health's Oncotype DX breast cancer recurrence test. For this trial, MetaStat will use samples from the ECOG 2197 trial, a 776-patient cohort in which researchers previously validated Oncotype DX.
On the market, MetaSite and MenaCalc will compete with multi-gene expression breast cancer recurrence tests, such as Oncotype DX and Agendia's MammaPrint, on price and turnaround time, Rick Pierce, MetaStat's VP of investor relations, told GenomeWeb. Multi-gene expression tests carry a list price of several thousand dollars and can take up to two weeks to return results. MetaStat is hoping to keep the price of its test under $1,000 and return results in three to five days.
"These gene panels are indirectly predicting distant metastases by showing upregulation of certain growth and anti-death genes," Gustavson said. "Ours are mechanistic-based tests where we're quantifying the direct mechanism of metastatic disease."
In commercializing its tests, MetaStat plans to start in the community hospitals, "where physicians want good answers at an affordable price, but probably don't have access to more sophisticated treatments that you get at a place like MD Anderson or Dana-Farber," Pierce noted. MetaStat will eventually also target the major cancer centers, where it hopes to make its tests part of the armamentarium that oncologists have to garner deeper insights into patients' tumor characteristics.
The subset of patients who fall in the intermediate risk category after getting tested on multi-gene expression panels, is one group for which MetaStat hopes its tests could provide more definitive guidance. Usually, patients in this intermediate-risk category get chemotherapy, but not all may need to. "We can help restratify a portion of those patients," Pierce said. "This would be valuable for saving payors money, but more importantly, it would be of tremendous value to patients' lives and outcomes."
The third study MetaStat will conduct will be one in which researchers investigate whether MenaCalc and MetaSite can predict whether invasive breast cancer patients are likely to respond to chemotherapy. The chemo-predictive capability for Oncotype DX has set it apart from other breast cancer recurrence tests and helped its early inclusion in treatment guidelines and insurance coverage policies.
"Our plan is to have the results of all three of these trials by time of commercialization in 2016," Gustavson said.
Pierce added that MetaStat is exploring commercialization partnerships as it refines the launch strategy for its tests.