SEATTLE, June 1, 2016 /PRNewswire/ -- Resolution Bioscience today announced that its Resolution ctDx™ blood-based NGS platform was used to detect ALK fusions, ALK resistance mutations and other driver mutations in patients' circulating tumor DNA in a phase I/II clinical trial of the ALK inhibitor X-396 (ensartinib), Xcovery's lead drug candidate in development for the treatment of ALK-positive non-small cell lung cancer (NSCLC). The results of this study will be presented at the 2016 ASCO meeting in Chicago and in a publication to follow.
In the Phase I/II trial of X-396, patients with advanced non-small cell lung carcinoma (NSCLC) and ALK+ FISH results were given X-396 on 28-day cycles, and a standard blood draw was carried out at baseline and then day 1 of each cycle. X-396 was well tolerated and induced responses in both crizotinib-naïve and crizotinib-resistant patients. Blood-based NGS using the ctDx™ platform was performed retrospectively on all collections.
Sequencing results demonstrated the ability of the ctDx™ platform to identify the exact locations of ALK-fusion events, as well as to identify other driver and resistance mutations - all by using a single assay on patient plasma. Serial sequencing showed decreases in the allelic frequency of ALK fusions in responding patients and increases at time of progression. ALK fusions and other somatic variants were regularly detected at frequencies below 0.5%. The assay also discovered novel ALK fusion events in patients, including fusions to the PRKAR1A gene and to non-genic regions. Interestingly, patients with multiple ALK fusion events were also discovered, suggesting that the blood-based approach provides access to an increased spectrum of tumor heterogeneity that was undetected by FISH.
"We are glad to see that the ctDx™ blood-based assay seems to be able to select patients for therapy as well as to monitor for response and the development of acquired resistance in patients. Longitudinal monitoring is rarely possible with current tissue-based collection methods," said Chris Liang, CSO of Xcovery.
"We are excited about the opportunity to characterize these clinical samples. The ability of our ctDx™ platform to identify and longitudinally track genetic mutations, including fusion rearrangements and resistance mutations, allows for a unique look into tumor evolution not possible from tissue biopsies. We believe this ability will greatly enhance the treatment of cancer patients and provide powerful new information to therapeutic developers," said Mark Li, CEO of Resolution.
Date and Time: Saturday June 4th, 8:00am-11:30am
Title: Plasma genotyping of patients enrolled on the expansion phase I/II trial of X-396 in patients with ALK+ non-small cell lung cancer (NSCLC).
Abstract Number: 9056
Poster Board Number: 379
Resolution Bioscience's (Bellevue, WA) best-in-class circulating cfDNA platform was the first to demonstrate comprehensive detection of all somatic mutation types in blood, including point mutations, indels, copy number changes and fusions down to 0.1% allelic frequency. The robust platform allows simultaneous discovery of de-novo novel fusion events and detection of canonical fusions. The company develops custom cfDNA assays to support clinical use and companion diagnostics. The company's mission is to transform cancer outcomes by providing noninvasive diagnostic tools to guide the development and clinical implementation of personalized treatment strategies.
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SOURCE Resolution Bioscience