FDA Grants 2 Breakthrough Device Designations to Signatera MRD Test

The FDA has granted 2 breakthrough device designations to cover new intended uses of the Signatera molecular residual disease (MRD) test developed by Natera, Inc., according to a recent announcement.¹

The new designations will support the development of the test through phase 3 clinical trials as a companion diagnostic to 2 cancer treatments. With the breakthrough device designation granted in 2019, the Signatera MRD test now has 3 designations for use across several cancer types and indications.

“We are committed to working with the FDA and with our biopharma partners to validate the use of the Signatera MRD test across a broad range of solid tumor indications,” Fayyaz Memon, vice president of Regulatory Affairs at Natera, commented in the press release. “These 2 new breakthrough device designations will help us accelerate our mission to bring life-saving diagnosis and treatment to [patients with] cancer as early as possible.”

The custom-build circulating tumor DNA test was developed to monitor treatment and assess for MRD in patients who have previously been diagnosed with cancer. Available for use in the clinical and research settings, the Signatera MRD test is both personalized and tumor-informed; specifically, it provides a customized blood test that is tailored to fit the specific signature of clonal mutations that are found in that individual’s tumor. The personalized approach increases accuracy with regard to detecting whether residual disease is present or absent from a blood sample.

“Signatera is intended to detect and quantify how much cancer is left in the body, to detect recurrence earlier and to help optimize treatment decisions,” according to Natera. “Signatera test performance has been clinically validated in multiple cancer types including colorectal, non–small cell lung, breast, and bladder cancers.”

A positive result per the Signatera MRD test predicts relapse with overall positive predictive value more than 98%.^2-5 In patients with colon cancer who were ctDNA positive were 40 times more likely to experience disease recurrence compared with those who are negative (HR, 43.5; 95% CI, 9.8-193.5; P <.001).²

In patients with breast cancer, ctDNA was detected ahead of clinical or radiologic relapse in 16 of 19 relapsed patients, translating to a sensitivity of 89%.3 In patients with lung cancer, the sensitivity of the test was demonstrated to be 92%.⁴

Lastly, in patients with bladder cancer, the presence of ctDNA was found to be highly prognostic at the time of diagnosis prior to chemotherapy (HR, 29.1; P = .001). Following cystectomy, ctDNA analysis was found to accurately identify all patients with metastatic relapse during monitoring, translating to an 100% sensitivity and 98% specificity.⁵

References

1. FDA grants two new breakthrough device designations for Natera’s Signatera MRD test. News release. Natera Inc. March 24, 2021. Accessed March 24, 2021. https://bit.ly/3lLSuIs
2. Reinert T, Henriksen TV, Christensen E, et al. Analysis of plasma cell–free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer. JAMA Oncol. 2019;5(8):1124-1131. doi:10.1001/jamaoncol.2019.0528
3. Coombes RC, Page K, Salari R, et al. Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence. Clin Cancer Res. 2019;25(14):4255-4263. doi:10.1158/1078-0432.CCR-18-3663
4. 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
5. 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;37(18):1547-1557. doi:10.1200/JCO.18.02052