Natera's Phase III Study in Bladder Cancer Treatment: A Leap Forward in Personalized Medicine

Natera has launched the ARCHER trial to explore advancements in treating muscle-invasive bladder cancer. The phase III study aims to determine if a reduced radiation treatment schedule can match the effectiveness of the existing standard treatment. Natera's Signatera molecular residual disease test will be included as a secondary endpoint to evaluate outcomes. The trial's results could lead to significant changes in bladder cancer therapy, emphasizing tailored treatment strategies.

Natera, Inc. (NASDAQ: NTRA), a leader in cell-free DNA and precision medicine, has announced the activation of the ARCHER trial, a phase III study sponsored by NRG Oncology through the National Cancer Institute’s National Clinical Trials Network. The ARCHER trial, designated as NRG-GU015, aims to evaluate whether a shorter course of radiation therapy can achieve outcomes comparable to the current standard of care for muscle-invasive bladder cancer (MIBC).

The study will enroll more than 100 sites across the U.S. and Canada and will incorporate Natera's personalized, tumor-informed molecular residual disease (MRD) test, Signatera, as a pre-specified secondary endpoint. Signatera will be used to monitor real-time circulating-tumor DNA (ctDNA) clearance patterns, serving as a predictive marker of treatment response and recurrence. The test will also assess urine tumor DNA as an exploratory endpoint.

The ARCHER trial seeks to address the high interest in identifying therapeutic approaches that can achieve promising clinical outcomes while maximizing patient quality of life. MIBC accounts for approximately one-quarter of all bladder cancer cases in the United States and typically requires aggressive treatment [1]. By utilizing Signatera, the study aims to detect early molecular signs of disease recurrence and refine clinical surveillance methods beyond traditional imaging and cystoscopy.

The launch of ARCHER will expand Natera’s breadth of MIBC clinical evidence, following 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 [2].

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.