Signatera™ Blood Test Detects Bladder Cancer Relapse Up to Eight Months Earlier Than Current Clinical Standards

SAN CARLOS, Calif., May 7, 2019 /PRNewswire/ — Natera, Inc. (NASDAQ: NTRA) today announced the publication of a clinical validation study demonstrating that its Signatera™ molecular residual disease (MRD) test was highly prognostic of recurrence in patients with bladder cancer, and it identified recurrence up to 8.2 months earlier than current clinical standards with 100 percent sensitivity.¹ Results were published in the May 2019 issue of the Journal of Clinical Oncology.

The prospective study analyzed 656 blood samples from 68 patients with muscle invasive bladder cancer from Aarhus University in Denmark. The study used Natera’s Signatera research-use-only test, a personalized, tumor-informed method for detecting molecular residual disease, to evaluate circulating tumor DNA (ctDNA) in plasma samples collected at diagnosis, during chemotherapy, before cystectomy, and serially during the surveillance period.

Results demonstrated that a positive Signatera test result was the strongest prognostic marker of disease recurrence and long-term patient outcomes, relative to all other risk factors. At time of diagnosis (pre-treatment), ctDNA-positive patients had a recurrence rate of 46 percent, compared with 3 percent for ctDNA-negative patients. During surveillance after cystectomy, ctDNA-positive patients had a recurrence rate of 93 percent, compared with no recurrence for ctDNA-negative patients.

In addition, serial ctDNA analysis following cystectomy revealed that Signatera correctly identified all patients with metastatic disease progression up to 8.2 months (245 days) ahead of radiographic imaging with 100 percent sensitivity and 98 percent specificity. 

"This study shows Signatera’s power to predict which patients are at highest risk for recurrence, and to detect metastatic disease sooner to guide earlier medical interventions," said Alexey Aleshin, M.D., MBA, Natera’s oncology medical director. "Until now, it has been clinically difficult to evaluate which muscle invasive bladder cancer patients have benefited most from chemotherapy. Now, we have a precise tool that is much more predictive of treatment response."

An estimated 549,000 cases of bladder cancer are diagnosed worldwide each year,² and it is the sixth most common cancer in men.² The overall five-year survival rate is 77 percent, but the five-year survival rate for locally advanced bladder cancer is just 35 percent.³  

The study, titled Early Detection of Metastatic Relapse and Monitoring of Therapeutic Efficacy by Ultra-Deep Sequencing of Plasma Cell-Free DNA in Patients with Urothelial Bladder Carcinoma, can be found here.

About Signatera™

Signatera is the first circulating tumor DNA (ctDNA) test custom-built for molecular treatment monitoring and molecular residual disease (MRD) assessment. The test is available for research use only (RUO) until its clinical launch planned for Q2 2019. The Signatera methodology differs from currently available liquid biopsy tests, which test for a fixed panel of therapeutically relevant genes. Signatera provides each individual with a customized blood test tailored to match the clonal mutations found in that individual’s tumor tissue. This maximizes accuracy for detecting the presence or absence of MRD in a blood sample, even at levels down to a single mutant molecule in a tube of blood. Signatera also allows researchers to track additional mutations of interest, up to several hundred mutations, for clinical studies.

The body of evidence on the utility of Signatera is growing, with multiple studies demonstrating the Signatera RUO method’s ability to detect molecular residual disease, measure treatment response, and identify recurrence months or years earlier than the standard of care for a variety of cancer types, including breast cancer, early stage non-small cell lung cancer, bladder cancer, and colorectal cancer.^{1, 4-7} Based on numerous studies across multiple cancer types, a positive Signatera RUO result without further treatment has predicted clinical relapse over 98 percent of the time.^{1, 4-7}

Natera will also offer a research-use-only service for plasma-based whole exome sequencing to create a personalized assay when tissue is not available, or reflexively for Signatera ctDNA positive cases, to characterize resistance mutations, actionable mutations, neoantigens, and tumor evolution. The service will interrogate approximately 20,000 genes from ctDNA to detect somatic mutations, representing a significant increase in coverage over most commercially available fixed liquid biopsy panels. If ordered as a combined service, researchers can first use Signatera to monitor patients for the presence or absence of ctDNA, and for positive patients they can reflex to a plasma exome to characterize tumor evolution using the same exact DNA library sample. Natera expects the service to become available in the second half of 2019.

About Natera

Natera is a global leader in cell-free DNA testing. The mission of the company is to change the management of disease worldwide with a focus on reproductive health, oncology, and organ transplantation. Natera operates an ISO 13485-certified and CAP-accredited laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA) in San Carlos, Calif. It offers a host of proprietary genetic testing services to inform physicians who care for pregnant women, researchers in cancer 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, our collaborations with commercial partners such as medical institutions, contract laboratories, laboratory partners, and other third parties, whether the results of clinical 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.

This test was developed by Natera, Inc. a laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA). This test has not been cleared or approved by the U.S. Food and Drug Administration (FDA). Although FDA does not currently clear or approve laboratory-developed tests in the U.S., certification of the laboratory is required under CLIA to ensure the quality and validity of the tests.

Contacts
Investor Relations: Mike Brophy, CFO, Natera, Inc., 650-249-9090
Media: Andrea Sampson, Sullivan & Sampson, 714-374-6174, asampson@sullivanpr.com

References

1. Christensen E, Birkenkamp-Demtröder K, Sethi H, et al. Early detection of metastatic relapse and monitoring of therapeutic efficacy by ultra-deep sequencing of plasma cell-free DNA in patients with urothelial bladder carcinoma. J Clin Oncol. 2019. DOI:10.1200/JCO.18.02052.
2. Bray F, Ferlay J, Soerjomataram, I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin. 2018;68:394–424
3. Bladder cancer statistics. https://www.cancer.net/cancer-types/bladder-cancer/statistics. Accessed May 6, 2019
4. Coombes RC, Page K, Salari R, et al. Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence. Clin Cancer Res. 2019. DOI:10.1158/1078-0432.
5. Magbanua M, Brown-Swigart L, Hirst G, et al. Personalized serial circulating tumor DNA (ctDNA) analysis in high-risk early stage breast cancer patients to monitor and predict response to neoadjuvant therapy and outcome in the I-SPY 2 TRIAL. Data presented at spotlight session: San Antonio Breast Cancer Symposium; December 5, 2018. Abstract 1259
6. Reinert T, Henriksen TV, Rasmussen MH, et al. Serial circulating tumor DNA analysis for detection of residual disease, assessment of adjuvant therapy efficacy and for early recurrence detection in colorectal cancer. Poster presented at: European Society for Medical Oncology Annual Congress; October 21, 2018; Munich, Germany. Abstract 456PD.
7. Abbosh C, Birkbak NJ, Wilson GA, et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017; 545(7655):446–451.

SOURCE Natera