FDA has granted a breakthrough device designation to the Signatera test from Natera Inc, San Carlos, Calif, for use in the postsurgical detection and quantification of circulating tumor DNA (ctDNA) in the blood of patients previously diagnosed with certain types of cancer, and in combination with certain drugs. FDA’s designation will help to accelerate the agency’s assessment and review of Signatera as an in vitro diagnostic for use in pharmaceutical trials.

The Signatera methodology differs from currently available liquid biopsy tests, which test for a fixed panel of therapeutically relevant genes. Signatera is the first ctDNA test custom-built for each patient based on the unique mutations in an individual patient’s tumor. Signatera provides each individual with a customized blood test tailored to match the clonal mutations found in that individual’s tumor tissue. This process maximizes accuracy for detecting the presence or absence of measurable residual disease (MRD) in a blood sample, even at levels down to a single mutant molecule in a tube of blood. Signatera also enables researchers to track additional mutations of interest, up to several hundred mutations, for clinical studies.

A number of clinical studies have demonstrated that Signatera is capable of identifying measurable residual disease up to 2 years earlier than standard imaging.1–5 The studies have also shown the utility of the test across bladder, breast, colorectal, and non-small cell lung cancers. Signatera test status is the most significant predictor of long-term patient outcomes after surgery and treatment, relative to all other clinical and pathology factors.1–5

“This breakthrough device designation is a significant step forward in our commercial strategy, helping to clear the path for Natera to participate in registrational drug trials that use Signatera for patient selection and study enrichment,” says Solomon Moshkevich, general manager of the oncology and transplant businesses at Natera. “This milestone directly supports our stated goal of achieving $40 million to $50 million in cumulative pharma contracts by the end of 2019.”

“We are delighted to work with FDA in the context of the breakthrough device program,” says Steve Chapman, CEO of Natera. “This designation validates our belief that Signatera will truly change the way cancer patients are diagnosed and treated, ultimately leading to better treatment decisions and improved clinical outcomes.”

Evidence about the utility of the Signatera test is increasing, as multiple studies have demonstrated the method’s ability to detect measurable residual disease, measure treatment response, and identify recurrence months or years earlier than the current standard of care.1–5 Based on numerous studies across multiple cancer types, a positive Signatera test result without further treatment has predicted clinical relapse over 98% of the time.1–5

For further information, visit Natera.


  1. Coombes C, Page K, Salari R, et al. Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence. Clin Cancer Res. Epub before print, April 16, 2019; doi: 10.1158/1078-0432.CCR-18-3663.
  1. Magbanua MJM, Brown-Swigart L, Hirst GL, 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 [abstract 1259, online]. Presentation at the San Antonio Breast Cancer Symposium, San Antonio, Texas, December 4–8, 2018. Available at: www.abstracts2view.com/sabcs/view.php?nu=SABCS18L_1259&terms=. Accessed June 26, 2019.
  1. Birkenkamp-Demtröder K, Christensen E, Sethi H, et al. Longitudinal assessment of multiplex patient-specific ctDNA biomarkers in bladder cancer for diagnosis, surveillance, and recurrence [abstract 86P]. Poster presented at the annual congress of the European Society for Medical Oncology, Munich, October 19–23, 2018. Ann Oncol. 2018;29(suppl 8):mdy269.084; doi: 10.1093/annonc/mdy269.084.
  1. 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 [abstract 456PD]. Poster presented at the annual congress of the European Society for Medical Oncology, Munich, October 19–23, 2018. Ann Oncol. 2018;29(suppl 8):mdy281.004; doi: 10.1093/annonc/mdy281.004.
  1. Abbosh C, Birkbak NJ, Wilson GA, et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017;545(7655):446–451; doi: 10.1038/nature22364.

 Featured image

: Natera Signatera kit.