Landmark IMvigor011 Trial Validates ctDNA-Guided MIBC Therapy

Topline results from the randomized, phase 3 IMvigor011 clinical trial (NCT04660344) demonstrate a new paradigm in the management of muscle-invasive bladder cancer (MIBC).¹ The study, utilizing the Signatera circulating tumor DNA (ctDNA) test, showed that selecting patients based on molecular residual disease (MRD) status can identify a subgroup that benefits significantly from adjuvant immunotherapy. Specifically, for patients who tested positive for ctDNA after surgery, treatment with atezolizumab (Tecentriq) led to statistically significant and clinically meaningful improvements in both disease-free survival (DFS) and overall survival (OS).

“The results of IMvigor011 are very significant, opening the door for a new treatment paradigm for bladder cancer patients who are positive for recurrence on a molecular level but have no evidence of disease on imaging,” said Thomas Powles, MBBS, MRCP, MD, lead principal investigator of the study, Barts Cancer Institute QMUL, in a press release. “We look forward to presenting the positive results later this year.”

The IMvigor011 trial is the first prospective, randomized phase 3 study to validate a personalized, ctDNA-guided approach in MIBC. The trial was designed to evaluate the efficacy of adjuvant atezolizumab vs placebo in patients with MIBC who had undergone radical cystectomy and tested positive for ctDNA in the bloodstream. Approximately 760 patients were enrolled in the initial surveillance phase and underwent serial ctDNA testing using the Signatera assay for up to 12 months postsurgery. The assay, which is a personalized and tumor-informed test, detects minute quantities of ctDNA to track MRD with high sensitivity. Patients who were found to be ctDNA-positive and showed no signs of recurrence on imaging were then randomized to receive either atezolizumab or a placebo.

The positive outcomes for the ctDNA-positive treatment group represent a major step forward for patients with MIBC, a cohort that has historically faced limited treatment options following surgery. The presence of ctDNA postsurgery is a strong prognostic marker for disease recurrence, with studies consistently showing that ctDNA-positive patients have a poor prognosis.

About IMvigor011

The IMvigor011 trial is a global, double-blind, randomized phase 3 study sponsored by Genentech.² Its primary goal is to evaluate outcomes in patients with high-risk MIBC after cystectomy using Natera's personalized MRD test, Signatera. The trial aims to determine if Signatera can help personalize treatment decisions, specifically by identifying patients who may be spared from adjuvant treatment.

Patients were serially tested with Signatera for up to 12 months postcystectomy. If a patient tested Signatera MRD-positive at any point during this surveillance window, they were randomized to receive either the anti–PD-L1 immunotherapy atezolizumab or a placebo. Patients who remained Signatera-negative throughout the testing window did not receive this additional treatment but continued with radiographic imaging.

Key Surveillance Findings

The analysis presented at the European Association of Urology (EAU) Congress 2024 focused on 171 patients with high-risk MIBC who remained Signatera MRD-negative during the surveillance window of the IMvigor011 trial.¹ Key findings included:

• OS rates: 100% at 12 months and 98% at 18 months in patients who remained serially MRD-negative.
• DFS rates: 92% at 12 months and 88% at 18 months in patients who remained serially MRD-negative.

These results suggest that patients with MIBC who remain MRD-negative on serial Signatera testing after surgery may be able to avoid adjuvant treatment.

REFERENCES:

1. IMvigor011 Bladder Cancer Trial Achieves Positive Results, with Signatera™ Strongly Predicting Adjuvant Immunotherapy Benefit. Natera. August 18, 2025. Accessed August 18, 2025. https://tinyurl.com/4vdvzd5w

2. A Study of Atezolizumab Versus Placebo as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Bladder Cancer Who Are ctDNA Positive Following Cystectomy (IMvigor011). ClinicalTrials.gov. Updated June 22, 2025. Accessed August 18, 2025. https://clinicaltrials.gov/study/NCT04660344