NEW YORK (GenomeWeb) – Liquid biopsy firm Inivata has published an analytical validation of its InVisionFirst-Lung test, a targeted sequencing assay that detects mutations in the blood of lung cancer patients to help physicians decide which drugs to treat them with.
The results, published this month in PLOS One, suggest that the test's analytical performance is strong. It can pick up mutations at low frequencies, with high specificity, and with high concordance to results using digital PCR assays.
Because there may be only a scant amount of mutated cancer DNA in a blood sample with a vast background of normal DNA fragments, high sensitivity is a requirement for liquid biopsy assays, and potentially something that could become a point of distinction as tests begin to compete for clinical adoption in different niches.
InVision is based on a technology called targeted amplicon sequencing (TAm-seq), developed by Tim Forshew and Muhammed Murtaza and spun out from Nitzan Rosenfeld's laboratory at the University of Cambridge in 2014.
Inivata's current test is specific to non-small cell lung cancer, which is becoming the first arena where oncologists are beginning to embrace liquid biopsy in clinical practice.
It is also the first cancer type for which the FDA has approved a liquid biopsy test as a companion diagnostic — Roche's blood-based Cobas EGFR Mutation Test v2.
However, some clinicians and clinical researchers have noted in recent months that they are eschewing use of the Roche test in favor of other assays that use digital PCR or next-gen sequencing because of their superior sensitivity compared to the Roche kit, or because they allow for multiplexed analyses of different alterations.
Inivata's analytical validation publication highlights the dilemma faced by these clinicians, not just in regard to evaluating competitors to the FDA-approved Roche test, but potentially in choosing between an increasing number of available platforms.
In its report, Inivata wrote that InVision showed over 99 percent sensitivity for detecting single nucleotide variants present at a variant allele fraction between 0.25 percent and 0.33 percent. For indels, the sensitivity at 0.25 percent VAF was more than 92 percent.
According to Inivata CEO Michael Stocum, those numbers are better than what other liquid biopsy platforms have shown in similar evaluations.
To arrive at their conclusions, researchers from the company analyzed nearly 1,000 samples — including clinical samples collected from NSCLC patients and healthy volunteer donors, and contrived samples designed to represent a wide spectrum of genetic aberrations and VAFs.
Importantly, even at increasingly low VAFs — down to 0.06 percent — investigators reported that they could still pick up more than half of SNVs.
This is important as Inivata seeks to shore up these results with additional proof of the test's clinical validity, or how the test performs when applied prospectively to real patient samples. It's also crucial if the company were to move toward promoting the test not just for stratification of patients with advanced NSCLC, but for other indications like monitoring for the presence of tumor DNA during drug treatment, or after surgery in early-stage patients.
Stocum said in an interview last week that Inivata's clinical validation study, which began in the fall of 2016, has now completed, and was the core of a dossier submitted to Medicare contractor Palmetto under its MolDx program last fall.
"We expect and hope for a positive outcome from that process," Stocum said.
Gaining coverage for InVision for Medicare patients would clearly support Inivata in its push into the clinic, and help it keep pace with competitors like Guardant Health, whose draft local coverage decision from Palmetto last year is still awaiting finalization.
While the exit of Genomic Health from the NGS liquid biopsy race this month highlights the hurdles panel-based tests face in convincing clinicians of their utility, Stocum said that Inivata believes that in lung cancer at least, doctors have an increasingly strong rationale for turning to comprehensive tests over single-gene assays.
As the question of utility sorts out, Stocum said, validity then becomes a more crucial factor in competition for clinical adoption.
Based on its validation, Inivata is confident in its ability to compete in terms of analytical validity, he added, though "its going to take time and utilization in the market to see how that plays out and which tests are the most effective."
US Food and Drug Administration approval has in some ways been a shorthand for clinicians — in knowing whether a medical test is analytically valid or not. But with the rise of laboratory-developed tests that operate outside of the agency's oversight, that has shifted dramatically in the cancer space as evidenced by the fact that the oncology community is conflicted over whether to use the FDA-approved Roche Cobas EGFR test, to turn to other methods, or even to adopt broader NGS panels.
Guardant Health is so-far the first of the NGS liquid biopsy companies to announce plans to go through FDA, saying recently that it received an Expedited Access Pathway designation for its Guardant360 test.
According to Stocum, Inivata isn't at a place where it can publicize any plans in that vein, though it is considering options.