Benzinga | Jun 16, 2021 11:22AM EDT

Natera Highlights Publication Of Prospective, Randomized Study Validating Signatera For Prediction Of Immunotherapy Benefit In Nature Journal

Natera,Inc. (NASDAQ:NTRA), a pioneer and global leader in cell-free DNA testing, today announced the publication of a new study in Nature, validating the ability of its personalized and tumor-informed circulating tumor DNA (ctDNA) assay, Signatera, to predict outcomes with immunotherapy in a randomized clinical trial. The study, which can be found here, is Signatera's 12th peer-reviewed publication and is the first publication that shows the predictive capabilities of a molecular residual disease (MRD) test in a large, randomized, multi-center study.

"In this study, we show that personalized ctDNA analysis is highly accurate not only for identifying molecular residual disease, but also for predicting treatment outcomes with immunotherapy," said Thomas Powles, M.D., professor, Barts Cancer Institute, and first author of the study. "This opens new avenues for patient stratification, an important step in the drive towards personalized cancer therapy."

This data comes on the heels of Natera's announcement of the prospective Phase III IMvigor011trial, sponsored by Genentech. The study uses Signatera as a companion diagnostic to evaluate the safety and efficacy of adjuvant treatment with atezolizumab (Tecentriq)(r) in patients with muscle-invasive urothelial carcinoma (MIUC) who are MRD-positive after surgery.

The paper reports results from a prospective ctDNA analysis of 581 MIUC patients who were enrolled in IMvigor010, a Phase III randomized study that evaluated adjuvant treatment with the PD-L1 inhibitor atezolizumab versus observation. While the intent-to-treat all-comer analysis failed to meet its primary endpoint, the ctDNA-positive subset (37%) had significantly improved clinical outcomes upon treatment, compared to observation alone. The median overall survival in Signatera-identified ctDNA-positive patients treated with atezolizumab was 25.8 months compared to 15.8 months in those under observation alone. ctDNA status was assessed after surgery and prior to the start of therapy, and at week six of the treatment regimen.

Key findings from the study include:

* ctDNA-positive patients after surgery (37%) derived significant treatment benefit and had a 41% improvement in overall survival (HR 0.59)

* ctDNA-negative patients after surgery (63%) derived no treatment benefit

* The rate of ctDNA clearance was higher in the treatment arm (18.8%) compared to the observation arm (3.8%), indicating that ctDNA status/clearance can serve as an early indicator of treatment response

* Patients who responded to atezolizumab had significantly different RNA signatures from the patients who did not respond

"These findings have significant implications for patient care, the cost of care and how we collectively approach the design of clinical trials in the adjuvant setting," said Alexey Aleshin, M.D., Natera's vice president of medical affairs, oncology and co-author of the study. "For the first time, we have definitive evidence that Signatera can identify patients who will benefit from immunotherapy and monitor response in real time. We believe this may provide immediate clinical utility to better identify patients likely to benefit from adjuvant therapy in routine clinical practice."