FDA premarket approval sought for Signatera CDx test in MIBC

Natera has submitted an application to the FDA seeking premarket approval (PMA) of its Signatera CDx test as a companion diagnostic molecular residual disease (MRD) test for the selection of patients with muscle-invasive bladder cancer (MIBC) who may benefit from adjuvant treatment with atezolizumab (Tecentriq).¹

“Submitting this PMA represents an important step toward making MRD-guided treatment a reality for patients with muscle-invasive bladder cancer,” said Alexey Aleshin, MD, MBA, general manager of oncology and corporate chief medical officer at Natera, in a news release from the company.¹ “If approved, we believe Signatera CDx has the potential to be the first companion diagnostic MRD test that helps guide treatment decisions and improve outcomes for patients.”

The application is backed by data from the phase 3 IMvigor011 trial (NCT04660344), which met its primary end point by demonstrating that circulating tumor DNA (ctDNA) could accurately predict which patients would derive benefit from treatment with atezolizumab.² Data showed that among those who were ctDNA-positive, patients who received treatment with atezolizumab achieved a statistically significant and clinically meaningful improvement in disease-free survival (DFS) and overall survival (OS) vs those who received placebo.

In total, the double-blind study included 761 patients, of whom 250 tested ctDNA-positive. These patients underwent randomization in a 2:1 fashion, with 167 assigned to the atezolizumab group and 83 to the placebo group. Participants received either intravenous atezolizumab or placebo every 4 weeks for up to 1 year. The primary end point was DFS, with OS as a key secondary end point.

At a median follow-up of 16.1 months, in patients who were ctDNA-positive, the median DFS was 9.9 months (95% CI, 7.2 to 12.7) in the atezolizumab group vs 4.8 months (95% CI, 4.1 to 8.3) in the placebo group (HR, 0.64; 95% CI, 0.47 to 0.87; P = .005). Further, the median OS for patients who were ctDNA positive was 32.8 months (95% CI, 27.7 to NE) in the atezolizumab group vs 21.1 months (95% CI, 14.7 to NE) for the placebo group (HR, 0.59; 95% CI, 0.39 to 0.90, P = .01).

Overall, the findings suggest that ctDNA-based detection of MRD may help identify patients who have a high risk of recurrence following cystectomy and may benefit from adjuvant immunotherapy.

Previously reported results from the study also showed favorable outcomes among patients who tested serially negative on ctDNA testing.³ Among these patients, the DFS was 95% at 12 months and 88% at 24 months. According to the authors, these results indicate that patients who remain ctDNA-negative on serial testing may safely avoid adjuvant treatment.

REFERENCES

1. Natera Submits Signatera™ CDx PMA to FDA. News release. Natera, Inc. February 2, 2026. Accessed February 2, 2026. https://www.businesswire.com/news/home/20260129560151/en/Natera-Submits-Signatera-CDx-PMA-to-FDA

2. Powles T, Kann AG, Castellano D, et al. ctDNA-Guided Adjuvant Atezolizumab in Muscle-Invasive Bladder Cancer. N Engl J Med. 2025;393(24):2395-2408. doi:10.1056/NEJMoa2511885

3. Natera announces positive surveillance analysis from the randomized phase III IMvigor011 trial in muscle-invasive bladder cancer. News release. Natera, Inc. April 5, 2024. Accessed February 2, 2026. https://www.natera.com/company/news/natera-announces-positive-surveillance-analysis-from-the-randomized-phase-iii-imvigor011-trial-in-muscle-invasive-bladder-cancer/