Natera Inc, San Carlos, Calif, a global leader in cell-free DNA testing, has announced an agreement with Bristol-Myers Squibb to use Natera’s Signatera circulating tumor DNA (ctDNA) assay in a phase 2 study of adjuvant use of Opdivo (nivolumab) in the treatment of non-small cell lung cancer (NSCLC).

The study will use the Signatera ctDNA assay to select patients who have minimal residual disease after surgical resection to receive adjuvant standard of care with or without Opdivo (nivolumab). Study sponsors anticipate first patient enrollment in 2019, once Natera completes validation of its Signatera ctDNA assay under the requirements of the Clinical Laboratory Improvement Amendments of 1988 (CLIA). The study represents the first prospective clinical trial using the Signatera ctDNA assay in adjuvant NSCLC.

Charles Swanton, MD, PhD, senior group leader of the translational cancer therapeutics laboratory at the Francis Crick Institute, will lead the study. Natera’s previous research collaboration with Swanton and the UCL Cancer Institute team was important for the development and early clinical validation of Natera’s approach in NSCLC.1

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Alexey Aleshin, MD, MBA, Natera.

Lung cancer is the second most common cancer, excluding skin cancer, and is the leading cause of cancer death in the United States. Each year, more people die of lung cancer than of breast, colon, and prostate cancers combined.2 The 5-year survival rate is 56% when localized and detected early; however, only 16% of cases are detected at this stage. The 5-year survival rate for patients with nonlocalized tumors that have spread to other organs is only 5%.3

“We are excited to use our ctDNA assay to potentially help define a new way to detect and treat early-stage lung cancer patients,” says Alexey Aleshin, MD, MBA, oncology medical director at Natera. “We are also pleased to have been chosen as the first ctDNA assay to be used in a prospective outcomes study to inform adjuvant NSCLC treatment.”

“Our goal is to potentially use the learnings from this study to serve as Natera’s framework with other companies to investigate novel approaches from the metastatic setting in early-stage treatment,” adds Matthew Rabinowitz, PhD, CEO of Natera. “We believe that our technology will potentially enable treatment selection for patients most likely to benefit.”

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Matthew Rabinowitz, PhD, Natera.

Natera estimates that approximately 12.6 million people in the United States have been diagnosed with early-stage cancer across tumor types.3,4 In addition to this trial, Natera has initialed agreements to participate in 24 other studies with 19 companies, covering most of the top 10 pharmaceutical companies. The studies include prospective trials to correlate clinical response with ctDNA levels for personalized cancer vaccines as well as targeted therapies. Combined with previously disclosed investigator-initiated studies in bladder, breast, colorectal, and lung cancers, these studies will lay the foundation for Signatera’s clinical validation as a pan-cancer assay.

Signatera, which is currently labeled for research use only, is the first ctDNA assay custom built for treatment monitoring and minimal residual disease assessment. The Signatera methodology differs from currently available liquid biopsy assays, which test for a panel of genes independent of an individual’s tumor. By contrast, Signatera provides each patient with a customized blood test tailored to match the mutations found in that individual’s tumor tissue, thereby maximizing the sensitivity and specificity of the test. For clinical studies, the assay also allows researchers to track up to several hundred additional mutations of interest.

A recent study demonstrated Signatera’s ability to detect residual disease, measure treatment response, and identify recurrence up to 11 months earlier than the standard of care for early-stage NSCLC, with 93% sensitivity and zero false positives.1 Study data presented at the 2018 meeting of the American Association for Cancer Research showed successful results from bladder and colorectal cancer studies, including median detection points of ctDNA that were 4.3 and 7.9 months, respectively, ahead of clinical relapse detection.5,6

To learn more, visit Natera.


  1. Abbosh C, Birkback NJ, Wilson GA, et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017; 545:446–451; doi: 10.1038/nature22364.
  1. Key Statistics for Lung Cancer [online]. Atlanta: American Cancer Society, 2018. Accessed September 4, 2018.
  1. Lung Cancer Fact Sheet [online]. Vancouver, Wash: American Lung Association, 2018. Accessed September 4, 2018.
  1. Statistics [online]. Bethesda, Md: National Cancer Institute [SEER Program], 2018.. Accessed September 4, 2018.
  1. Birkenkamp-Demtröder K, et al. Sequencing of plasma cfDNA from patients with locally advanced bladder cancer for surveillance and therapeutic efficacy monitoring [abstract 3653]. In: Proceedings of the annual meeting of the American Association for Cancer Research; Chicago, April 14–18, 2018.
  1. Andersen C, et al. Personalized circulating tumor DNA analysis to monitor colorectal cancer [abstract 159]. In: Proceedings of the annual meeting of the American Association for Cancer Research, Chicago, April 14–18, 2018.