On June 17, 2019 Resolution Bioscience, Inc., reported the publication of a blinded performance evaluation between two cell-free DNA (cfDNA) next-generation sequencing (NGS) assays (Press release, Resolution Bioscience, JUN 17, 2019, View Source [SID1234537121]). The publication reports that the team of scientists, led by lung cancer researchers and clinicians at Dana-Farber Cancer Institute, found that the Resolution ctDx-Lung assay identified more actionable gene fusion mutations than Guardant Health’s Guardant360 test. The peer-reviewed manuscript, "Sensitivity of next-generation sequencing assays detecting oncogenic fusions in plasma cell-free DNA," was released online ahead of publication in Lung Cancer.
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Plasma genotyping has shown the ability to identify actionable, targetable mutations to drive personalized therapy for patients with advanced non-small cell lung cancer (NSCLC). However, leading commercial platforms have generated variable results when detecting complex variations, such as oncogenic gene fusions or copy number variations. In this comparison study, a cohort of 169 NSCLC patients with Guardant360 plasma results was screened for the presence of gene fusions based on previous tumor tissue analysis. Scientists at Dana-Farber used the Resolution kit in their lab to analyze the plasma of 16 patients who had a rearrangement in their tumor. All personnel involved in sample analysis were blinded to tumor genotype and Guardant360 results.
The Resolution assay detected 13 out of 16 (81.3%) fusions (allele frequency range 0.17-62.8%), while the Guardant360 test detected only seven (43.8%) fusions (allele frequency range 0.3-8.2%). For cases detected by both assays, the Resolution technology identified the mutation at a median of 7% higher allele frequency, which is indicative of a higher capture rate of breakpoint bearing cfDNA that increases overall sensitivity. For the six patients in which a fusion was detected by the Resolution assay but not by Guardant360, the average time to treatment discontinuation was 15.2 months (full range of 3-34 months).
"The Resolution liquid biopsy platform is designed to provide a fast, accurate, and non-invasive solution for mutationally comprehensive tumor genotyping," said Mark Li, CEO of Resolution Bioscience. "While this was a small study, we measure our success one patient at a time. Two patients with a fusion undetected by Guardant360 were on treatment for more than 30 months."
Dana-Farber scientists hypothesized that the Resolution assay offers more efficient hybridization to cfDNA fragments due to its use of tiled, short (˜40 nt) capture probes rather than more common 120 nt probes.
"Our targeted sequencing platform was designed from the ground up for analysis of cfDNA fragments. The shorter probes maintain high specificity while allowing better detection of the low amounts of mutation-bearing fragments often found in plasma," said Li. "Importantly, scientists at the Dana-Farber Cancer Institute performed the assay within their lab, demonstrating the potential of a distributed model."
Scientists presented the early results of this retrospective liquid biopsy comparison study between Resolution’s ctDx-Lung assay and Guardant Health’s Guardant360 test at this year’s American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. To view the full manuscript, please visit View Source
About Resolution Bioscience’s Technology
The Resolution liquid biopsy assays are powered by the company’s patented cfDNA NGS analysis platform, which includes proprietary targeted capture NGS chemistry and tightly coupled, cloud-based bioinformatics. Resolution’s technology has now been recognized as novel by the US Food and Drug Administration and has been cited in several important research publications and presentations. For example:
The Resolution HRD assay was recently granted Breakthrough Device Designation by the US Food and Drug Administration (FDA).
The company was the first to demonstrate detection of all four major types of mutations in a blinded clinical study led by scientists at Dana-Farber Cancer Institute. The team determined the assay has the potential to be implemented broadly for patient care and translational research.
Resolution was also the first company to demonstrate gene deletion detection in cfDNA in a study led by scientists at Vanderbilt University in small cell lung cancer. The team determined that cfDNA sequencing allows for improved monitoring of disease burden, depth of response to treatment, and timely warning of disease relapse in patients.
Resolution recently published 97% clinical response data with Memorial Sloan Kettering Cancer Center for non-small cell lung cancer patients who received plasma-directed therapy selection from Resolution’s assay. With more than 950 patients enrolled, the ongoing study is the largest prospective study of stage II, III, or IV NSCLC aimed at demonstrating clinical response and outcomes based upon plasma-directed therapy selection.
In a recent AstraZeneca publication, Resolution had the highest positive predictive value (PPV) and lowest false positive rate amongst four leading NGS liquid biopsy companies in a blinded comparison study.