ctDNA Test is Predictive of Adjuvant Atezolizumab Benefit in MIBC

A preliminary analysis of patients from the phase 3 IMvigor011 who tested negative with the Signatera test presented at the 2024 European Association of Urology Annual Meeting showed that patients who remained negative on serial testing had OS rates of 100% and 98% at 12 and 18 months after surgery, respectively.

Having a positive Signatera circulating tumor DNA (ctDNA) test is predictive of a treatment benefit with atezolizumab (Tecentriq) in patients with muscle-invasive bladder cancer (MIBC), according to a news release from the assay’s developer, Natera, Inc.¹

Specifically, results from the phase 3 IMvigor011 trial (NCT04660344) revealed that patients with MIBC who tested positive with the ctDNA test demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) and overall survival (OS) with adjuvant atezolizumab vs those who did not test positive. Furthermore, developers are expecting trial data to be published at an upcoming medical conference.

Additionally, a preliminary analysis of patients from the phase 3 IMvigor011 who tested negative with the Signatera test was presented at the 2024 European Association of Urology Annual Meeting, showing that patients who remained negative on serial testing had OS rates of 100% and 98% at 12 and 18 months after surgery, respectively.² The respective DFS rates were 92% and 88% after surgery.

“The results of IMvigor011 are significant, opening the door for a new treatment paradigm for patients with bladder cancer who are positive for recurrence on a molecular level but have no evidence of disease on imaging,” Thomas Powles, MBBS, MRCP, MD, professor of genitourinary oncology, lead for Solid Tumor Research, director of Barts Cancer Institute at St Bartholomew’s Hospital at Queen Mary University of London, and lead principal investigator of the study, said in the news release.¹ “We look forward to presenting the positive results later this year.”

Patients with MIBC with a positive Signatera test in the global, open-label phase 3 trial were randomly assigned to receive atezolizumab or placebo. Patients in the investigational arm received intravenous atezolizumab at 1680 mg on day 1 of each 28-day cycle for up to 12 cycles or a year.³ Patients in the placebo arm received a placebo given intravenously on day 1 of 28-day cycles. Treatment continued until disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination.

About 760 patients underwent serial Signatera testing for up to 12 months following surgery. Those who tested negative with the Signatera test continued to undergo follow-up with radiographic imaging and ctDNA molecular residual disease (MRD) testing.

The primary end point of the trial was DFS. Secondary end points included OS, disease-specific survival, distant metastasis-free survival, quality of life, and safety.

Patients with histologically confirmed MIBC; a Tumor, Node, Metastasis (TNM) classification of tumor stage ypT2-4a or ypN+ and M0 in those treated with prior neoadjuvant chemotherapy (NAC) or pT2-4a or pN+ and M0 in those not treated with prior NAC; who underwent surgical resection of MIBC; and those with a tumor PD-L1 expression per immunohistochemistry evaluable by central testing of representative tumor tissue were eligible for the surveillance phase of the trial.

For the treatment phase of the trial, those with a positive ctDNA test, an absence of residual disease or metastases, an ECOG performance status of 0 to 2, a life expectancy of at least 12 weeks, and those with adequate hematologic and end-organ function were included for trial enrollment.

The phase 3 IMvigor011 trial used the Signatera test in patients with MIBC to detect MRD in the bloodstream following surgery and predict adjuvant atezolizumab benefit.

Developers will finalize a premarket approval application to the FDA for Signatera as a companion diagnostic for atezolizumab in patients with MIBC following cystectomy.

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

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://tinyurl.com/37k9fvwa
2. 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://tinyurl.com/yynz5575
3. 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://tinyurl.com/4rtuw8j7