• Randomized study aims to reduce treatment burden for patients and utilizes Signatera to monitor for disease recurrence

AUSTIN, Texas / Aug 28, 2025 / Business Wire / Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and precision medicine, today announced the activation of the NRG Oncology trial, ARCHER (NRG-GU015), a randomized, phase III study in muscle-invasive bladder cancer (MIBC). The study is evaluating whether a shorter course of radiation can achieve outcomes comparable to the current standard of care. It prospectively incorporates Signatera, Natera’s personalized, tumor-informed molecular residual disease (MRD) test, as a pre-specified secondary endpoint.

MIBC accounts for approximately one-quarter of all bladder cancer cases in the United States and typically requires aggressive treatment.¹ Bladder-sparing treatment options are increasing in patient care, and there is a high interest in identifying therapeutic approaches that can achieve promising clinical outcomes while maximizing patient quality of life.²

The ARCHER trial is sponsored by NRG Oncology through the National Cancer Institute’s National Clinical Trials Network. It is expected to have enrollment from more than 100 sites across the U.S. and Canada. Signatera will be collected and reported to investigators during treatment and follow-up at defined timepoints. The test will enable investigators to evaluate real-time circulating-tumor DNA (ctDNA) clearance patterns in each treatment arm as a predictive marker of treatment response and recurrence. Natera will also assess urine tumor DNA as an exploratory endpoint. Signatera has been clinically validated in MIBC to detect recurrence months before standard imaging and to independently predict recurrence risk following curative-intent therapy.³

“With Signatera as a key assessment in the ARCHER trial, we aim to evaluate ctDNA dynamics to detect early molecular signs of disease recurrence in real time and refine our clinical surveillance toolbox beyond imaging and cystoscopy,” said Catherine Spina, M.D., Ph.D., co-chair of translational science for the study. “By utilizing ctDNA to monitor treatment response and recurrence, we hope to improve clinical outcomes for patients with MIBC.”

“By exploring whether we can safely reduce the intensity and duration of therapy without compromising outcomes, ARCHER has the potential to ease patient burden and improve quality of life,” said Minetta Liu, M.D., chief medical officer of oncology at Natera. “The use of serial Signatera testing in ARCHER represents an important step forward in determining how MRD insights can guide more precise patient management.”

The launch of ARCHER will expand Natera’s breadth of MIBC clinical evidence, where data has proven how ctDNA testing can benefit patients. That includes the recent read-out of positive topline results from the randomized phase III IMVigor011 trial, which demonstrated Signatera’s ability to predict adjuvant immunotherapy benefit in patients post-cystectomy.

References

1. Holzbeierlein J, Bixler BR, Buckley DI, Chang SS, Holmes RS, James AC, et al. Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/SUO Guideline (2017; Amended 2020, 2024). Journal of Urology [Internet]. 2024 Jul 1 [cited 2025 Aug 12];212(1):3–10. Available from: https://doi.org/10.1097/JU.0000000000003981
2. Laukhtina E, Moschini M, Teoh J, Shariat S. Bladder sparing options for muscle-invasive bladder cancer. Curr Opin Urol;34 (6): 471-76.
3. Christensen E, Birkenkamp-Demtröder K, Sethi, H, Shchegrova S, Salari R, Nordentoft I, et al. (2019). 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. Journal of Clinical Oncology, 37(18), 1547–1557. https://doi.org/10.1200/JCO.18.02052

About Natera

Natera™ is a global leader in cell-free DNA and genetic testing, dedicated to oncology, women’s health, and organ health. We aim to make personalized genetic testing and diagnostics part of the standard-of-care to protect health and inform earlier, more targeted interventions that help lead to longer, healthier lives. Natera’s tests are supported by more than 300 peer-reviewed publications that demonstrate excellent performance. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas, and San Carlos, California. For more information, visit www.natera.com.

Forward-Looking Statements

All statements other than statements of historical facts contained in this press release are forward-looking statements and are not a representation that Natera’s plans, estimates, or expectations will be achieved. These forward-looking statements represent Natera’s expectations as of the date of this press release, and Natera disclaims any obligation to update the forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to whether the results of clinical or other studies will support the use of our product offerings, the impact of results of such studies, our expectations of the reliability, accuracy, and performance of our tests, or of the benefits of our tests and product offerings to patients, providers, and payers. Additional risks and uncertainties are discussed in greater detail in "Risk Factors" in Natera’s recent filings on Forms 10-K and 10-Q, and in other filings Natera makes with the SEC from time to time. These documents are available at www.natera.com/investors and www.sec.gov.