NEW YORK (GenomeWeb) – Exosome Diagnostics has published a new study validating its exosome-based liquid biopsy assay for EGFR T790M testing in lung cancer patients, suggesting that its approach offers improved sensitivity over the only blood-based platform currently approved by the US Food and Drug Administration for this indication.
The study appeared as a preprint last month in Clinical Cancer Research. Â Authors from Exosome, with collaborators from Clovis Oncology and two medical centers, analyzed 210 patient plasma samples with the company's combined exosomal RNA and circulating DNA platform.
According to the investigators, the Exosome Dx test had 92 percent sensitivity and 89 percent specificity  compared to tissue biopsy results.
Exosome's T790M assay is currently for research use only, but resistance mutation testing in non-small cell lung cancer has rapidly become one of the first clinical areas where blood-based gene tests are being embraced by clinicians.
Only one technology, Roche's Cobas EGFR Mutation Test v2, has been approved by the FDA for detecting EGFR sensitizing and resistance mutations in blood samples. But academic and hospital labs have sometimes chosen to adopt other technologies and several companies currently market laboratory-developed liquid biopsy tests that either target EGFR alone or as part of a larger panel of mutations.
In promoting its validation results, Exosome Dx specifically highlighted that its assay's sensitivity and specificity in the study outshone what Roche reported in the experimental evidence that supported FDA approval of its Cobas test.
Johan Skog, Exosome Dx's chief scientific officer, said that the company can't discuss its commercial timeline for releasing a clinical T790M test, but reiterated the conclusions of the study regarding the potential superiority of Exosome Dx's platform to other marketed technologies.
"The thing about FDA-approved tests [is that] they are often based on older technologies, whereas there are more modern approaches emerging all the time that are more sensitive."
Exosome Dx's technology is based on an isolation platform it calls the ExoLution Plus kit, which co-isolates exosomal RNA/DNA and circulating cell-free DNA in a single step. This is then followed by quantitative PCR assays for whichever target or targets are of interest.
The company has only launched one product for clinical use so far — a urine-based prostate cancer test that uses a three-gene expression signature to generate a risk score for patients ranging from 0 to 100. A score greater than 15.6 is associated with an increased likelihood of high-grade prostate cancer on a subsequent biopsy.
According to Skog, Exosome is still building up to clinical launch of tests for EGFR sensitizing mutations and T790M, having decided to focus its commercial and marketing activities over the last year on its prostate cancer test.
But the firm has clearly been collecting evidence to support a clinical launch in lung cancer, whenever that takes place, mainly by highlighting the potential of its platform to outperform assays that look only at circulating cell-free DNA.
For example, investigators from the company recently published another study in which they found that mutated EGFR copy numbers in samples of mixed cell-free DNA and isolated exosomal nucleic acids were up to 10-fold higher than what was seen in samples of cfDNA alone.
In the recently published validation, the researchers applied the Exosome Dx test to plasma samples from 102 biopsy-confirmed T790M-positive patients and 108 confirmed T790M-negative patients. Using tissue-biopsy results as the gold standard, the Exosome-based method was 92 percent sensitive and 89 percent specific. Importantly, according to the authors, the assay also showed high sensitivity — 88 percent — in patients with intrathroracic disease, who have proved challenging to test using other liquid biopsy methods.
According to Skog, because of the rarity of T790M in NSCLC, the number of samples in the study was robust in context. "An N of 210 in this study is really quite remarkable, I think," he said.
"Some studies in this area have been biased with a large number of patients who have a high metastatic load, and that gives you a higher sensitivity. But we had a high number of these intrathoracic patients and our sensitivity in that group was very similar [to the other subjects]," he added.
Entering the clinical market for this niche, Exosome will not be alone in positioning itself as a superior alternative to the FDA-approved Roche platform. Clinicians have reported, for example, adopting droplet-based PCR methods that claim higher sensitivity than the Cobas platform, as well as broader sequencing-based LDTs like Inivata's or Guardant Health's, which boast the ability to profile multiple markers in a single test, something clinical guidelines in lung cancer have begun to endorse.
However, others in the clinical sphere, including powerful advisory groups like the American Society for Clinical Oncology, have also pushed back against the adoption of overly broad and unproven assays in liquid biopsy testing for lung cancer.
A recent report jointly authored by ASCO and the College of American Pathologists, for example, argued that clinical validity data for most liquid biopsy tests remains unproven.
Considering this type of guidance, Roche's Cobas may continue to enjoy a leg up over new entrants due to its status as an FDA-endorsed companion test.Â