Sysmex Inostics’ OncoBEAM™ RAS CRC testing supports clinical outcome improvements for metastatic colorectal cancer patients rechallenged with anti-EGFR therapy

Baltimore, Maryland, 2020.08.27 – Sysmex Inostics, Inc., a global leader and pioneer in blood-based circulating tumor DNA (ctDNA) analysis for oncology, today announces the publication of a clinical study evaluating RAS mutation status in circulating tumor DNA (ctDNA) of colorectal cancer (CRC) patients undergoing anti-EGFR antibody therapy (cetuximab or panitumumab) rechallenge using the OncoBEAM RAS CRC test in two different multicenter Japanese retrospective trials, JACCRO CC-08 and JACCRO CC-09.

OncoBEAM RAS CRC is a test that uses BEAMing technology, an enhanced digital PCR method optimized for high sensitivity blood-based mutation detection for metastatic colorectal cancer (mCRC) patients. In this study, investigators utilized the highly sensitive nature of OncoBEAM testing to explore the clinical value of monitoring changes in plasma RAS mutations in CRC patients during treatment with anti-EGFR antibody therapy.

Colorectal cancer continues to be one of the leading causes of cancer-related deaths globally. Treatment of mCRC patients with anti-EGFR monoclonal antibodies have demonstrated significant improvements in the survival of patients with wild-type RAS tumors. mCRC patients being considered for anti-EGFR therapy rechallenge could greatly benefit the overall patient survival by undergoing initial plasma testing to establish RAS mutation status at baseline, as well as performing subsequent tests to monitor RAS mutation dynamics during treatment. By receiving regular blood draws throughout the anti-EGFR rechallenge treatment, patients would benefit from periodic OncoBEAM RAS testing, which would in turn deliver valuable insights for clinicians in assessing therapy response.

The study published in JCO Precision Oncology by Sunakawa et al., demonstrated that RAS mutations were found in 38% of CRC patients after receiving the first course of anti-EGFR mAb therapy, but prior to rechallenge treatment. The disease control rate (DCR) was 33% in patients with RAS mutations in ctDNA, whereas it was 80% in patients without RAS mutation detected by OncoBEAM at baseline. The data also showed that patients with RAS mutations detected just before anti- EGFR mAb rechallenge had no survival benefit from rechallenge treatment. Moreover, post-progression survival time after rechallenge was worse in patients with RAS mutations than in patients without mutations at disease progression. The emergence of RAS mutations during rechallenge treatment at disease progression is therefore useful for predicting outcomes of anti- EGFR mAb therapy rechallenge.

“We found that the OncoBEAM RAS CRC assay was not only effective in monitoring the resistance to anti-EGFR therapy, but was also important in helping us determine the efficacy of the rechallenge treatment and therefore predict patients who would have favorable outcomes. Overall, our novel findings support the value of using the ultrasensitive OncoBEAM RAS liquid biopsy test in the clinical management of CRC patients receiving anti-EGFR mAb as rechallenge treatment. ” stated Dr. Yu Sunakawa, MD, PhD, Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki, Japan.

Besides results of this publication, a new prospective observational trial “REMARRY (UMIN000036424)” has been initiated with over 100 patients recruited as of June 2020. This clinical trial, supported by SCRUM-Japan MONSTAR-SCREEN, will expand the evaluation of patient-specific dynamics in ctDNA RAS mutational status as a predictor of anti-EGFR mAb rechallenge efficacy. Overall, the aggregate results from these trials should strongly support the clinical utility of performing longitudinal plasma OncoBEAM RAS testing in monitoring tumor response during anti-EGFR antibody therapy.

The publication, titled “RAS Mutations in Circulating Tumor DNA and Clinical Outcomes of Rechallenge Treatment with Anti-EGFR Antibodies in Patients with Metastatic Colorectal Cancer,” was published in JCO Precision Oncology, July 28, 2020, by Yu Sunakawa et al.:

The poster, titled “REMARRY and PURSUIT trials: Liquid biopsy-guided rechallenge of anti-EGFR monoclonal antibody for patients with RAS/BRAF V600E wild-type metastatic colorectal cancer” was presented at ESMO World Congress on Gastrointestinal Cancer 2020 by Hiromi Nakajima et al.:

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Sysmex Corporation received Insurance Coverage in Japan for Liquid Biopsy RAS Gene Mutation Testing for CRC Using High-Sensitivity Digital PCR

Kobe, Japan, 2020.08.03 – Sysmex Corporation (Chairman and CEO: Hisashi letsugu) announced today that it has received approval for insurance coverage for blood-based RAS gene mutation testing for colorectal cancer using the OncoBEAM™ RAS CRC Kit. The coverage went into effect on August 1, 2020.

With this regulatory approval, even when it is difficult to obtain in vivo diagnostics (biopsy) on a sample taken from tumor tissue, RAS gene mutation testing using the kit may be performed with a minimal physical and mental burden on patients when it is necessary, owing to the fact that it uses the patient’s blood as a sample. This will have the effect of optimizing decisions on the administration of anti-EGFR monoclonal antibody drugs. Receipt of insurance coverage will also make it possible for us to provide more patients with testing to allow physicians to select an appropriate treatment method.

Currently, at the beginning of therapy, colorectal cancer patients treated with medication undergo RAS gene mutation testing using tumor tissue, the results of which inform a decision on whether or not to administer anti-EGFR monoclonal antibody drugs. Several studies have reported that re-challenge of anti-EGFR monoclonal antibody drugs is an effective treatment method for patients with recurrent colorectal cancer after treatment by anti-EGFR monoclonal antibody drugs, and that the RAS gene mutation status may change by the time of re-challenge from what it was in initial therapy. The relevant guidance published by the Japanese Society of Medical Oncology indicates that it is desirable to assess the gene mutation status several times over time to make appropriate re-challenge decisions based on the state at the time of relapse. As such, much has been expected from a practical application of liquid biopsy, which checks the RAS gene mutation status using the patient’s blood samples when biopsy may not be performed easily.

The OncoBEAM™ RAS CRC Kit is used to test samples of tumor-derived DNA (circulating tumor DNA, or ctDNA) suspended in the blood of colorectal cancer patients. Using BEAMing technology, the kit detects RAS gene mutations with a high degree of sensitivity (mutant allele frequency of no more than 1% in approximately 30% of mutation cases thus detected). As the first colorectal cancer liquid biopsy testing in Japan that provides auxiliary test data to determine the appropriateness of anti-EGFR monoclonal antibody drugs – Cetuximab and Panitumumab (gene recombination) – for patients with colorectal cancer, this product was approved as an in vitro diagnostic reagent in July 2019 and was covered under health insurance from August 1, 2020. Please note that an insurance-covered assay service for colorectal cancer using this product is also due to start in August 2020.

Performance of RAS gene mutation testing when it is necessary and with a minimal physical and mental burden on patients for whom biopsy is challenging to perform is expected to optimize the administration of anti-EGFR monoclonal antibody drugs. On the other hand, there is a possibility that this testing may deem patients whose ctDNA is not sufficiently leaked into the blood to have wild-type RAS, even though RAS gene mutation exists in tumor tissue. For patients with lung metastasis only, it is particularly necessary to prioritize testing using tumor tissue. Sysmex will remain committed to the provision of scientific information so that medical institutions may perform testing properly.

Going forward, Sysmex will continue to contribute to the advancement of personalized medicine by working on expanding testing opportunities for patients and providing testing and diagnostic technologies with high diagnostic value.

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  • “Sysmex Obtains First Manufacturing and Marketing Approval in Japan for Blood-Based RAS Gene Mutation Testing for Colorectal Cancer,” released on August 2, 2019
  • “Sysmex Presents Academic Report Related to the Clinical Utility of RAS Gene Mutation Testing for Colorectal Cancer Using Liquid Biopsy – Details of Report on Clinical Utility of OncoBEAM™ RAS CRC Kit presented at the American Society of Clinical Oncology Gastrointestinal Cancers
    Symposium 2020 (ASCO-GI 2020),” released on March 5, 2020

Sysmex Inostics’ Colorectal Cancer Blood-Based OncoBEAM™ RAS CE-IVD Test Shows Concordance with Standard of Care Tissue-Based RAS Testing

Baltimore, Maryland, 2020.08.05 – Sysmex Inostics, Inc., a global leader and pioneer in blood-based circulating tumor DNA (ctDNA) analysis for oncology, today announces the publication of a clinical study evaluating the performance of plasma RAS mutation testing with OncoBEAM RAS CRC as compared to standard of care tissue-based RAS testing in the United Kingdom (UK).

OncoBEAM RAS CRC is a CE-IVD test that uses BEAMing technology, an enhanced digital PCR method optimized for high sensitivity blood-based mutation detection for metastatic colorectal cancer (mCRC) patients. This is the first study of its kind in the UK with confirmatory testing performed across laboratories certified to run the OnocBEAM RAS CRC test. Investigators also utilized the highly sensitive nature of OncoBEAM testing to also explore the clinical value of detecting changes in plasma RAS mutation status in patients treated with anti-EGFR antibody therapy.

The overall percent agreement between the OncoBEAM assay and tissue-based testing for RAS mutations was 86.0% (86/100), with a 100% reproducibility of test results between three labs located in the UK, Germany, and Japan. This demonstrates that blood-based testing with an appropriate and well validated assay can serve as an alternative to tissue-based testing and can improve access to precision medicine globally.

Colorectal cancer (CRC) continues to be one of the leading causes of cancer-related deaths globally. Anti-EGFR monoclonal antibodies have demonstrated significant improvements in survival of patients with wild-type RAS tumors mCRC. However, tissue-based biomarker testing has been shown to present several challenges, such as tumor molecular heterogeneity, poor tissue quality, and logistical issues, which can contribute to delays in treatment initiation. Importantly, as patients undergo treatment with targeted therapies, insight into changing tumor molecular dynamics would require repeat tissue biopsies, which is not practical in routine clinical management. Since mCRC patients already undergo regular blood draws throughout treatment; testing with the OncoBEAM RAS assay can deliver valuable insights into tumor response.

The ability to draw serial blood samples and perform OncoBEAM ctDNA longitudinal analyses of RAS mutant allelic fraction (MAF) variation before and during anti-EGFR therapy provides opportunities to identify emerging RAS mutant clones early during treatment. This minimally invasive approach provides better visualization of treatment responses and failures, enabling personalized therapy approaches for mCRC patients, with the goal of improving outcomes. The lead and senior authors of the study, Dr. Theodora Germetaki and Dr. Mark Saunders, Department of Medical/Clinical Oncology, The Christie Hospital, Manchester, UK conclude: “We showed that 20% of patients showed a change in their RAS mutational status during treatment. These results demonstrate there is an opportunity to more precisely understand an individual patient’s tumor response using longitudinal plasma testing in order to establish new clinical decision points for the management of patients receiving EGFR inhibitor therapy.” Ongoing studies are exploring the outcomes and cost-effectiveness of OncoBEAM RAS testing to guide the management of anti-EGFR treatment in mCRC patients.

Overall, this study shows the value of an ultrasensitive OncoBEAM liquid biopsy RAS test in overcoming sampling bias associated with tissue biopsy to enable rapid turn-around time of molecular test results for more timely initiation of first-line treatment and early detection of RAS mediated resistance in patients receiving anti-EGFR therapy.

The publication, titled “Blood-based RAS mutation testing: concordance with tissue-based RAS testing and mutational changes on progression,” was published in Future Oncology July 27, 2020, by Theodora Germetaki, et al.

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 (ctDNA) mutation detection in oncology utilizing highly sensitive technologies such as OncoBEAMTM (digital PCR) and Plasma-Safe-SeqS (NGS). These technologies were initially developed by experts at the Johns Hopkins School of Medicine over a decade ago and this deep expertise in ctDNA analysis extends to the core of Sysmex Inostics’ 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, from discovery through companion diagnostics.

Sysmex Inostics’ OncoBEAMTM and Plasma-Safe-SeqS services are readily available to support clinical trials and research in oncology. In addition, OncoBEAMTM tests are available through a CLIA-certified laboratory for routine clinical analysis as well as distributed kit products in the EU.

Sysmex Inostics’ European headquarters for research & development GCP laboratory testing are located in Hamburg Germany; Sysmex Inostics’ US headquarters and CLIA-certified and GCP Clinical Laboratory is located in Baltimore, Maryland.

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