March 5, 2020
Sysmex Corporation

Sysmex Presents Academic Report Related to the Clinical Utility ofRAS Gene Mutation Testing for Colorectal Cancer Using LiquidBiopsy
Details of Report on Clinical Utility of OncoBEAMTM RAS CRC Kit presented at the American
Society of Clinical Oncology Gastrointestinal Cancers Symposium 2020 (ASCO-GI 2020)

Sysmex Corporation (HQ: Kobe, Japan; Chairman and CEO: Hisashi Ietsugu) provides notice that
Dr. Yu Sunakawa, Associate Professor in the Department of Clinical Oncology at the St. Marianna
University School of Medicine, presented his research findings at the American Society of ClinicalOncology Gastrointestinal Cancers Symposium 2020 (ASCO-GI 2020), held in San Francisco,California, the United States, from January 23 to 25, 2020. This research involved examining theutility of RAS gene1 mutation testing for colorectal cancer with liquid biopsy2 using BEAMing
technology3 (OncoBEAMTM RAS CRC Kit) to help guide treatment decisions for the re-challenge ofanti-EGFR monoclonal antibody therapy in patients with metastatic colorectal cancer (mCRC).
This research involved collaborative biomarker studies (JACCRO CC-084 and CC-09AR5)
conducted in cooperation with Sysmex and the Japan Clinical Cancer Research Organization(Location: Tokyo, Japan; Director: Dr. Fumimaro Takaku; “JACCRO”).
The overexpression of epidermal growth factor receptors (EGFR) on the surface of colorectal
cancer cells is known to promote their cellular proliferation. Numerous studies have shown thatanti-EGFR monoclonal antibody drugs are effective in preventing the proliferation of these cancer
cells; however, this therapy is not effective in patients whose colorectal tumors harbor RAS
mutations. Accordingly, decisions on the administration of anti-EGFR monoclonal antibody drugs
are usually made by assessing RAS gene mutations using resected tissues.
In recent years, clinical studies have actively investigated re-challenge of mCRC patients with antiEGFR therapy in an effort to improve the prognosis of patients who had previously responded to
1st-line anti-EGFR therapy treatment, but whose disease progressed during subsequent courses oftherapy in which anti-EGFR drugs were eliminated. In the process, it was reported that no clinicalbenefit by the re-challenge of anti-EGFR monoclonal antibody drugs on patients determined tohave wild-type RAS genes at the time of initial administration of anti-EGFR monoclonal antibody
drugs might be due to the emergence of RAS mutations during anti-EGFR therapy (Source: JAMAOncol. 2019;5(3):343-350).
Sysmex and JACCRO’s objective of this clinical research (JACCRO CC-08/09AR studies:retrospective6 study), was to examine a possible relationship between clinical outcomes of the antiEGFR re-challenge and the patient’s plasma RAS gene mutation status at the time of rechallenge.
This analysis was accomplished via liquid biopsy using OncoBEAMTM RAS CRC Kit to determine
the status of RAS gene mutations in circulating tumor DNA of mCRC patients prior to and duringanti-EGFR therapy re-challenge. Results showed that the re-challenge of mCRC patients with anti-

EGFR monoclonal antibody drugs improved the prognosis (progression-free survival7 and overallsurvival8) more for RAS wild-type patients than for RAS mutant patients. The results of thisresearch, presented at ASCO-GI 2020, indicated the clinical utility of liquid biopsy for RAS genemutation testing for colorectal cancer when deciding on the re-challenge of anti-EGFR monoclonal
antibody drugs.
Since obtaining tumor tissue biopsy samples from metastatic sites place undue physical burden on
patients, the liquid biopsy approach to determine RAS mutation status from blood samples isclearly a less invasive approach. Moreover, a liquid biopsy RAS mutation test gives the most timely
RAS mutation result at the time of recurrence and anti-EGFR re-challenge, rather than relying ondata obtained from testing archival tumor tissue samples. Going forward, progress on prospective6
studies to verify the effectiveness of decisions to re-challenge mCRC patients with anti-EGFR
monoclonal antibody drugs informed by OncoBEAMTM RAS CRC Kit for RAS gene mutation testingis expected to contribute to the clinical implementation and utility of this test in the re-challenge
treatment of anti-EGFR monoclonal antibody drugs.
By delivering new methods for diagnosing cancer to patients as quickly as possible, Sysmex istaking the lead in the global realization of personalized medicine and contributing to theenhancement of patients’ quality of life and advances in healthcare.

Data Sheet
Presented at:

American Society of Clinical Oncology Gastrointestinal Cancers Symposium 2020
(ASCO-GI 2020)
Date:
January 23–25, 2020
Poster number: 166
Title:RAS status in circulating-tumor DNA (ctDNA) and outcomes during rechallenge
treatments with anti-EGFR antibodies in metastatic colorectal cancer (mCRC)

The study was performed on the association between the presence of RAS gene mutations (RAS
wild-type patients (10 cases) and RAS mutant patients (6 cases)) and clinical outcome for patients
receiving rechallenge with Cetuximab or Panitumumab (16 cases). Prior to re-challenge of antiEGFR monoclonal antibody drugs, OncoBEAMTM RAS CRC Kit was used to measure RAS genemutations in plasma samples.
The results showed significantly longer survival for RAS wild-type patients than for RAS mutantpatients, both for progression-free survival (4.7 months for RAS wild-type patients and 2.3 months
for RAS mutant patients) and overall survival (16.0 months for RAS wild-type patients and 3.8months for RAS mutant patients). These results point to the clinical utility of RAS gene testing
using liquid biopsy prior to re-challenge of anti-EGFR monoclonal antibody drugs and are expected
to contribute to the determination of more appropriate treatment methods.

Terminology
1 RAS gene:As the likelihood is high that patients with RAS gene (KRAS/NRAS gene) mutations will notbenefit (prolongation of life, tumor reduction) from the administration of anti-EGFR drugs,
companion diagnostics may be performed to treat the gene mutation first.
2 Liquid biopsy:
Similar in performance to a biopsy, which is carried out on a sample taken from tissue such astumors, but which attempts to reduce the burden on the patient by using blood tests.
3 BEAMing technology:
This gene analysis method combines ultrahigh-sensitivity PCR and flow cytometry technologies.
BEAMing technology is used to capture individual DNA molecules with magnetic particles indroplets measuring several microns in diameter and then detecting the amplification of the DNA
molecules on the magnetic particles.
OncoBEAM RAS CRC Kit based on BEAMing technology is an in vitro diagnostic test (in vitrodiagnostic medical device registration number: 30100EZX00010000, MHLW-approved on July19, 2019, Manufactured and supplied by Sysmex) for detecting RAS mutations in ctDNA
extracted from the plasma of colorectal cancer patients.
4 JACCRO CC-08AR test:
Biomarker research related to a Phase II clinical trial on the re-challenge of Cetuximab fortertiary treatment of KRAS gene wild-type unresectable, advanced, recurrent colorectal cancer
to patients with a history of treatment with the anti-EGFR monoclonal antibody drug Cetuximab
5 JACCRO CC-09AR test:
Biomarker research related to a Phase II clinical trial on the re-challenge of Panitumumab for
tertiary treatment of KRAS gene wild-type unresectable, advanced, recurrent colorectal cancer
to patients with a history of treatment with the anti-EGFR monoclonal antibody drug
Panitumumab
6 Prospective/retrospective:
A prospective (forward-looking) study refers to an epidemiological survey method indicating that
information is to be gathered from the start of the survey forward into the future. By contrast,
retrospective (backward-looking) studies indicate the gathering of patient information retroactivefrom the start of the study.
7 Progression-free survival:
The period during treatment (following treatment) when cancer is not progressing and thecondition is stable.
8 Overall survival:
The period of a patient’s survival, beginning with the registration date of a clinical study.