NEW YORK – Epic Sciences recently announced DefineMBC, a liquid biopsy that includes both cell-based and cell-free analyses aimed at comprehensively profiling metastatic breast cancer when a tissue biopsy is unavailable.
The lab-developed test, or LDT, is designed to characterize tumors and monitor their evolution, including treatment response, by combining analyses of circulating tumor cells, single-cell whole-genome sequencing, and cell-free DNA sequencing into a single assay.
"By analyzing both CTCs and cfDNA through a single blood draw, DefineMBC provides a more comprehensive cancer profile than traditional cfDNA liquid biopsy assays, which are unable to assess protein expression," Rick Wenstrup, Epic's chief medical officer, said in an interview.
CTCs are identified and the levels of ER and HER2 protein expression levels are quantified via immunofluorescent staining followed by image analysis using a proprietary machine learning algorithm.
Individual CTCs are separated onto 96-well plates for single-cell sequencing aimed at detecting the amplified cancer-related genes through copy number variation, or CNV, analysis.
Epic analyzes cfDNA via next-gen sequencing on an Illumina platform, looking for single nucleotide variations, CNVs, microsatellite instability, and tumor mutational burden.
The clinical gene panel includes 56 genes, while an expanded panel used for research and clinical trials includes up to 500 genes and an ability to detect novel mutations.
"The clinical reporter will only go with the known mutations because those are the ones that are considered actionable," said Jason Christiansen, Epic's chief technology officer.
Wenstrup explained that the 56-gene panel consists of all the genes currently relevant to breast cancer. These include genes associated with available drugs or with drugs that are far enough along a development pipeline that they are likely to become available in the next year or so.
"And certainly, as we move forward and expand our technology into some other cancers, we will expand the panel appropriately," Wenstrup said.
DefineMBC results are delivered as an integrated clinical report that informs the treating physician of the presence of breast cancer cells, ER and HER2 protein expression, ERBB2 amplification, and actionable genomic alterations through cfDNA analysis.
The multi-analyte workflow incorporates technologies licensed from Scripps Research and the University of Southern California.
Epic currently processes all blood samples for the LDT at its CAP-CLIA lab in San Diego, California, with an approximate turnaround time of three weeks.
"The goal is to get it down into the two-week range right now," Christiansen said. "It's [currently] closer to three weeks just because we're still optimizing all of the workflow pieces to really bring that time down."
Epic is preparing to launch an early-access program in April, prior to a full commercial launch planned for July. The company has so far enrolled 15 out of a target 20 community cancer centers and is in the process of selecting others and reviewing program details.
Although Epic initially plans to launch DefineMBC only in the US, the company is evaluating overseas opportunities and supports several global clinical trials.
Epic expects to complete the validation of DefineMBC within the first quarter of this year, and to announce the full launch at the American Society of Clinical Oncology conference in June.
"We have completed all the necessary studies to launch DefineMBC as an LDT," Wenstrup said. "In addition, we have a robust clinical development plan to support an expansion of intended uses and applications."
While the company did not specify the new assay's specificity and sensitivity, it stated that it is submitting that data in a manuscript to a peer-reviewed journal.
DefineMBC enters a growing field of liquid biopsies aimed at detecting and characterizing cancers, and tracking cancer evolution and treatment response. Competitors include Guardant Health's Guardant360, Lucence's LiquidHallmark, and Invitae's planned tumor profiling LDT, meant to assess DNA, RNA, and protein biomarkers.
Within this space, Epic sees DefineMBC's more holistic approach to tumor profiling — and the incorporation of single-cell analysis — as a competitive edge.
"Single-cell sequencing analysis is not part of normal clinical analysis of breast cancer patients," Wenstrup commented.
"I really think DefineMBC gets into its own category," Christiansen added, "because most of the liquid biopsies today are not able to offer that cellular component."
"Multiplexing these already well-established techniques in a single analysis allows direct comparison to conventional medical histological analysis and is a good step towards overlapping conventional histological calls with what -omics can tell you in the same sample," said Prem Subramaniam, an associate research scientist studying cancer genetics at Columbia University, who has no ties to Epic Sciences.
Although Subramaniam praised the usefulness of performing multiple analyses in one run, he cautioned that the degree to which CTCs capture tumor heterogeneity – and therefore their utility in guiding therapy decisions – remains a topic of research.
Epic Sciences launched its first clinical product, a metastatic prostate cancer test called Oncotype Dx AR-V7 Nucleus Detect, in 2018. DefineMBC is the company's first breast cancer product. Epic has raised approximately $150 million to date and employs about 120 people.