Breakthrough Device Designations Granted to Novel MRD Test, Signatera

The FDA has granted 2 breakthrough device designations to the molecular residual disease test, Signatera.

The FDA has granted 2 breakthrough device designations to the molecular residual disease (MRD) test, Signatera, according to a press release by Natera, Inc.1

Signatera is a circulating tumor DNA (ctDNA) test meant to monitor MRD in patients with cancer. Currently, the test is available for both research and clinical use and has been granted a total of 3 breakthrough device designations by the FDA for multiple cancer types. The test has been used in clinical trials of patients with non-small cell lung cancer (NSCLC), breast cancer, colorectal cancer (CRC), and bladder cancer.

In order to detect MDR in circulating tumor DNA (ctDNA), the test uses a custom-built assay that is based on the mutation signature of each patient’s tumor. After the assay is designed, a patient’s blood sample is used to monitor the presence or absence of disease over time.

According to Natera, the test is 88% sensitive to CRC relapse, 89% sensitive to breast cancer relapse, 92% sensitive to lung cancer relapse, and 100% sensitive to bladder cancer relapse. The test is designed for both the adjuvant setting after surgery in order to help determine the need for chemotherapy and the surveillance setting.2

Currently, the test is being studied in the BESPOKE Study of ctDNA Guided Therapy in Colorectal Cancer(NCT04264702). The observational study has an estimated enrollment of 1000 participants with a target follow-up duration of 2 years. Primary outcomes of the study include Signatera’s impact on adjuvant treatment decisions and the rate of recurrence in patients using the test. Secondary outcomes include molecular residual disease clearance as assessed by the test, the percentage of patients who underwent surgery for oligometastatic recurrence, overall survival, and the survival of patients treated with adjuvant versus no adjuvant chemotherapy in patients with negative Signatera test results.

In order to participate, patients must be at least 18 years old or older and have been diagnosed with stage II or III colorectal cancer. Patients must also be planning to undergo or have undergone surgical resection of adenocarcinoma of the colon or rectum. Patients who are breastfeeding or pregnant are not eligible to participate. Additionally, patients with radiologic evidence of distant metastases or has a known rare inherited genetic condition are also excluded. Prior to the study, the patient must also have not initiated adjuvant chemotherapy.

In addition to the colorectal cancer adjuvant therapy, Signatera is being tested as a way to guide immunotherapy in melanoma, CRC, and NSCLC. The BESPOKE Study of ctDNA-Guided Immunotherapy (NCT04761783) has an aimed enrollment of 1539 participants. The primary outcome is the impact Signatera has on treatment decisions after the initiation of immunotherapy. Secondary outcomes included progression-free survival (PFS) according to ctDNA change, overall survival according to ctDNA change, PFS, and response rate.

Participants in the perspective arm will receive the Signatera test and use the results to guide immunotherapy, dosing schedule, and a treatment plan. Periodic blood collection will take place up to 2 years after they enter the study. Participants in the control arm must have undergone immunotherapy treatment and must have follow-up data available in their records for 2 years following the start of immunotherapy or death.

In order to participate, patients must be at least 18 years old and must have documented melanoma, NSCLC or CRC. Participants also must be eligible to receive an immune-checkpoint inhibitor. Patients that are pregnant or have a history of bone marrow or organ transplantation are ineligible to participate.

"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," said Fayyaz Memon, vice president of Regulatory Affairs at Natera, in a press release. "These two new breakthrough device designations will help us accelerate our mission to bring life-saving diagnosis and treatment to cancer patients as early as possible."2

1. FDA grants two new breakthrough device designations for Natera’s Signatera™ MRD test. News Release. March 24, 2021. Accessed March 25, 2021.
2. Signatera. Natera. Accessed March 25, 2021