IMvigor011: ctDNA test can predict adjuvant immunotherapy benefit in MIBC

Topline results from the phase 3 IMvigor011 trial (NCT04660344) suggest that the Signatera molecular residual disease (MRD) test may accurately predict which patients with muscle-invasive bladder cancer (MIBC) will benefit from adjuvant treatment with the immunotherapy atezolizumab (Tecentriq).

Overall, data showed that among those who were MRD-positive, patients who received adjuvant treatment with atezolizumab demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) and overall survival (OS) vs those who received treatment with placebo, Natera reported in a news release.¹ These results are expected to be shared at an upcoming medical conference.

“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 principal investigator Professor Thomas Powles, MBBS, MRCP, MD, of Barts Cancer Institute QMUL, in the news release.¹ “We look forward to presenting the positive results later this year.”

The Signatera circulating tumor DNA (ctDNA) test is used to detect MRD in patients’ bloodstream. For the study, the test was administered following cystectomy to determine which patients may benefit from adjuvant treatment with atezolizumab. In total, the double-blind trial enrolled 760 patients with MIBC who were at high risk for recurrence following surgery.² All patients underwent ctDNA testing for up to 12 months following surgery.

Patients who tested positive on MRD testing but were free of cancer recurrence on imaging were randomly assigned to adjuvant treatment with atezolizumab or placebo, administered every 4 weeks for 12 cycles or up to 1 year. Patients who consistently remained MRD-negative continued to be followed up with ctDNA testing and radiographic imaging.

The primary end point for the trial was investigator-assessed DFS. Secondary outcome measures included OS, independent review facility-assessed DFS, investigator-assessed disease-specific survival, investigator-assessed distant metastasis-free survival, time to confirmed deterioration of function and health-related quality of life, and ctDNA clearance, among other measures.

Based on these topline results, Natera plans to finalize an application to the FDA seeking premarket approval of the Signatera test as a companion diagnostic for the selection of patients with MIBC for adjuvant treatment with atezolizumab following surgery.  

“Importantly, IMvigor011 could change how resectable bladder cancer is managed for the tens of thousands of patients diagnosed with MIBC each year,” added Alexey Aleshin, MD, general manager of oncology and corporate chief medical officer at Natera, in the news release.¹

Additional Data from IMvigor011

Preliminary data from the IMvigor011 trial were shared at the European Association of Urology conference in April 2024.³ Data showed favorable outcomes among those who tested serially negative on MRD testing.

Among these patients, the OS rate was 100% at 12 months and 98% at 18 months. Further, DFS rates were 92% and 88% at 12- and 18-months, respectively. According to the authors, these results indicate that patients who remain MRD-negative on serial testing may safely avoid adjuvant treatment.

The IMvigor011 trial remains ongoing, with final completion expected in September 2026.² 

REFERENCES

1. IMvigor011 bladder cancer trial achieves positive results, with Signatera strongly predicting adjuvant immunotherapy benefit. News release. Natera, Inc. August 18, 2025. Accessed August 18, 2025. https://www.natera.com/company/news/imvigor011-bladder-cancer-trial-achieves-positive-results-with-signatera-strongly-predicting-adjuvant-immunotherapy-benefit/

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. Last updated June 22, 2025. Accessed August 18, 2025. https://clinicaltrials.gov/study/NCT04660344

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 August 18, 2025. https://www.natera.com/company/news/natera-announces-positive-surveillance-analysis-from-the-randomized-phase-iii-imvigor011-trial-in-muscle-invasive-bladder-cancer/