Sysmex Inostics' OncoBEAM(TM) demonstrates clinical validity and superior performance versus pan-cancer NGS for blood-based mutation detection for hepatocellular carcinoma

Hamburg, Germany (ots) - Data recently published in Clinical
Cancer Research (http://ots.de/0ZGZkf) the advantages of using an
ultra-high sensitivity test for detection of mutations which may
predict therapeutic efficacy for hepatocellular carcinoma (HCC).
Sysmex Inostics' OncoBEAM technology, a highly clinically validated
technology for circulating tumor DNA (ctDNA) analysis, was used to
determine RAS mutational status across a total of 1,318 patients
screened for two phase II studies which evaluated the efficacy of
refametinib monotherapy, and refametinib plus sorafenib in patients
with RAS-mutant unresectable or metastatic HCC.

Building on evidence from a prior phase II clinical trial which
showed that HCC patients whose tumors had a RAS mutation exhibited a
robust clinical response in comparison with patients who were
wild-type for RAS, investigators planned a prospective cohort to
evaluate RAS mutation status at the time of enrollment. Patients were
enrolled from 80 study centers in 21 countries across Asia, Europe,
and the USA. A primary challenge of enrollment across the world is
that patients with advanced or metastatic HCC do not typically
undergo tissue biopsy due considerable risk of complications;
therefore, molecular testing is not routinely performed in this
cancer. Further confounding enrollment is the low prevalence of RAS
mutations in patients with HCC, estimated to be 5%. To overcome these
challenges, investigators utilized OncoBEAM to screen patient plasma
for RAS mutations, as plasma testing can overcome the need for a
tumor biopsy procedure and deliver tumor mutational status via a
blood draw. Similar to other previously published studies across
various cancer types, OncoBEAM testing enabled investigators to
obtain information they would not otherwise receive in order to
inform eligibility for inclusion in these HCC studies.

Not only was OncoBEAM able to successfully detect RAS mutations
across this patient population at a rate consistent with the expected
RAS mutation rate for HCC via a simple, minimally-invasive blood
draw, but for a subset of patients who were also tested using a
broad, next-generation sequencing (NGS)-based method, OncoBEAM
demonstrated superior detection for low frequency RAS mutations. Out
of 27 patients determined to be RAS-positive by OncoBEAM who were
also tested using NGS, RAS mutation status was only confirmed in 12
patients (44.4%). The limited detection with NGS was most likely due
to the order of magnitude difference in the limit of detection
between the two assays (0.1% for NGS versus 0.02% for OncoBEAM). In
fact, the overall RAS mutation rate of the HCC patients screened with
OncoBEAM in these trials was 4.4%, which matched very closely with
previous reports in this population (5%).

Screening across a greater breadth of genomic targets via NGS can
sometimes reveal additional biomarker information which may inform
future research. For these two HCC phase II studies, NGS testing
revealed that outside of KRAS and NRAS the most frequently mutated
region was the TERT promoter, followed by TP53 and CTNNB1. However,
actionable mutations in genes other than RAS were rare, occurring in
less than 10% of the patients tested with NGS. These HCC clinical
studies highlight the utility of focused testing with an assay like
OncoBEAM: ultra-high sensitivity detection of rare mutant molecules
may provide benefits for patient welfare, and can ensure the most
time and cost-effective approach to screening and enrollment for
biomarker-driven trials when the biomarker relationship to disease
and therapeutic strategy has been established.

Publication Details

Lim H S et al. Phase II Studies with Refametinib or Refametinib
plus Sorafenib in Patients with RAS-Mutated Hepatocellular Carcinoma.
Clin Cancer Res 24:4650-4661 (2018).

About Sysmex Inostics

Sysmex Inostics, a subsidiary of Sysmex Corporation, is a
molecular diagnostic company that is a pioneer in blood-based
cell-free tumor DNA mutation detection in oncology utilizing highly
sensitive technologies such as OncoBEAM(TM) and SafeSEQ. These
technologies were initially developed by experts at the Johns Hopkins
School of Medicine over a decade ago and this deep expertise in ctDNA
anaylsis extends to the core of Sysmex Inostics' core capabilities
for technology development and implementation.

With more than 10 years of experience in liquid biopsy Sysmex
Inostics is a trusted partner to leading pharmaceutical companies,
advancing their efforts to bring the most effective personalized
cancer therapies to global markets.

Sysmex Inostics' OncoBEAM(TM) and SafeSEQ services are readily
available to support clinical trials and research in oncology. In
addition, OncoBEAM(TM) tests are available through a CLIA certified
laboratory for routine clinical analysis as well as distributed as
kit products in EU.

Sysmex Inostics' headquarters and GCP Service Laboratory are
located in Hamburg Germany; Sysmex Inostics' CLIA-certified and GCP
Clinical Laboratory is located in Baltimore, Maryland. For more
information refer to www.sysmex-inostics.com or email
info@sysmex-inostics.com.

Contact:
Sysmex Inostics
Press Release
Phone +49(0)40-3259070
Mail info@sysmex-Inostics.com

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