New Publication in Nature Cancer Demonstrates Signatera's Ability to Evaluate Tumor Response to Immunotherapy

SAN CARLOS, Calif., Aug. 3, 2020 /PRNewswire/ -- Natera, Inc. (NASDAQ: NTRA), a pioneer and global leader in cell-free DNA testing, today announced the publication of a manuscript in Nature Cancer¹ that validates the ability of its Signatera™ personalized circulating tumor DNA (ctDNA) technology to evaluate tumor response to immunotherapy in 25 different types of solid cancer. The full study can be found here.

"Although immune checkpoint inhibitors are an effective tool for treating many types of cancer, the decision to treat beyond radiological progression can sometimes be challenging due to potential pseudo-progression," explained Lillian Siu, MD, FRCPC, BMO Chair in Precision Cancer Genomics at the Princess Margaret Cancer Centre and lead investigator of the study. "We are delighted to have partnered with Natera on this landmark study, which shows that ctDNA-based surveillance using the Signatera test, in conjunction with imaging, can be used to identify true disease progression and thus help patients receive appropriate immunotherapy treatment."

Pseudo-progression is a phenomenon whereby the tumor appears larger on an initial scan during treatment before shrinking on subsequent scans, and it has been reported in up to 1 in 10 patients treated with immunotherapy.^2,3 The ability to distinguish true progression from pseudo-progression, earlier in the course of treatment, has emerged as a significant unmet clinical need.

The prospective phase II INSPIRE study, led by the Princess Margaret Cancer Centre in Toronto, followed patients with advanced solid tumors being treated with the immunotherapy drug, pembrolizumab. Whole exome sequencing was performed using tumor and matched normal DNA, and then bespoke ctDNA assays were designed using Signatera technology. ctDNA assessments were made at baseline in 94 patients, and every three cycles during treatment in 73 patients where serial plasma samples were available.

In the published manuscript, the study's authors concluded, "The findings from this prospective study suggest broad clinical utility for ctDNA-based surveillance in patients treated with immune checkpoint blockade."

Key findings from the study include:

• Signatera technology detected ctDNA before treatment in 98% of cases (92/94), emphasizing its validity as a universal biomarker across tumor types.
• ctDNA increase after just 6 weeks of treatment, together with increasing tumor volume on imaging, was identified in 42% of patients (30/73) and predicted treatment non-response with 100% accuracy. These patients received on average 6 extra weeks of treatment that potentially could have been avoided.
• ctDNA clearance at any time point during treatment was achieved by 16% of patients (12/73) and was associated with 100% overall survival with a median of 25.4 months of followup beyond first clearance.
• All findings were independent of tumor mutational burden (TMB) and PD-L1 status.

"With over 200,000 patients per year being treated with immunotherapy,⁴ we see a significant opportunity for serial use of Signatera to help physicians determine treatment response earlier," said Solomon Moshkevich, General Manager of Natera's oncology business. "We think this novel application could be as significant as Signatera's use case in early-stage colorectal cancer."

We thank Merck for contributing the drug for this clinical trial.

About Signatera
Signatera is a custom-built circulating tumor DNA (ctDNA) test for treatment monitoring and molecular residual disease (MRD) assessment in patients previously diagnosed with cancer. The test is available for clinical and research use, and, in 2019, it was granted Breakthrough Device Designation by the U.S. Food and Drug Administration (FDA). The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual's tumor. This maximizes accuracy for detecting the presence or absence of residual disease in a blood sample, even at levels down to a single tumor molecule in a tube of blood. 
Unlike a standard liquid biopsy, Signatera is not intended to match patients with any particular therapy. Rather, it is intended to detect and quantify how much cancer is left in the body, to detect recurrence earlier, and to help optimize treatment decisions. Signatera test performance has been clinically validated in multiple cancer types including colorectal, non-small cell lung, breast, and bladder cancers. Medicare has proposed insurance coverage for the use of Signatera in patients with Stage II or III colorectal cancer, and it is expected to finalize that coverage decision in 2020. Signatera has been developed and its performance characteristics determined by the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA). Although FDA is exercising enforcement discretion of premarket review and other FDA legal requirements for laboratory-developed tests in the US, certification of the laboratory is required under CLIA to ensure the quality and validity of the tests. 

About Natera
Natera is a pioneer and global leader in cell-free DNA testing. The mission of the company is to change the management of disease worldwide with a focus on women's health, oncology, and organ health. Natera operates ISO 13485-certified and CAP-accredited labs certified under the Clinical Laboratory Improvement Amendments (CLIA) in San Carlos, California, and Austin, Texas. It offers proprietary genetic testing services to inform obstetricians, transplant physicians, oncologists, and cancer researchers, including biopharmaceutical companies, and genetic laboratories through its cloud-based software platform. For more information, visit natera.com. Follow Natera on LinkedIn. 

Forward-Looking Statements
All statements other than statements of historical facts contained in this press release are forward-looking statements and are not a representation that Natera's plans, estimates, or expectations will be achieved. These forward-looking statements represent Natera's expectations as of the date of this press release, and Natera disclaims any obligation to update the forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to our efforts to develop and commercialize new product offerings, our ability to successfully increase demand for and grow revenues for our product offerings, whether the results of clinical or other studies will support the use of our product offerings, our expectations of the reliability, accuracy and performance of our screening tests, or of the benefits of our screening tests and product offerings to patients, providers and payers. Additional risks and uncertainties are discussed in greater detail in "Risk Factors" in Natera's recent filings on Forms 10-K and 10-Q and in other filings Natera makes with the SEC from time to time. These documents are available at www.natera.com/investors and www.sec.gov.

Contacts
Investor Relations: Mike Brophy, CFO, Natera, Inc., 650-249-9090
Media: Paul Greenland, VP of Corporate Marketing, [email protected]

References:

1. Bratman SV, Yang SYC, Iafolla MAJ, et al. Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nat. Cancer. 2020. https://www.nature.com/articles/s43018-020-0096-5
2. Borcoman E, Nandikolla A, Long G, Goel S, Tourneau CL. Patterns of Response and Progression to Immunotherapy. Am Soc Clin Oncol Educ Book. 2018;38:169-178.
3. Patel V. Progress on Pseudoprogression. The Pathologist. https://thepathologist.com/subspecialties/progress-on-pseudoprogression. Published 2018.
4. IQVIA™ Institute for Human Data Science Releases Global Oncology Trends 2019 Study: Record Number of Cancer Drugs Launched in 2018 across 17 Indications. IQVIA. https://www.iqvia.com/newsroom/2019/05/iqvia-institute-for-human-data-science-releases-global-oncology-trends-2019-study-record-number-of-c. Published 2019.

SOURCE Natera, Inc.

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