Adjuvant Atezolizumab Boosts DFS, OS in MIBC After Positive MRD Test

Adjuvant treatment with atezolizumab (Tecentriq) led to a statistically significant and clinically meaningful improvement in disease-free survival (DFS) and overall survival (OS) compared with placebo in patients with muscle-invasive bladder cancer (MIBC) who tested positive for minimal residual disease (MRD) using the Signatera assay and remained free from recurrence on imaging, according to topline data from the phase 3 IMvigor011 trial (NCT04660344).1

During the study, approximately 760 patients underwent surveillance for up to 12 months following surgery, and those who tested positive for MRD were randomly assigned to receive atezolizumab or placebo.

Full data from IMvigor011 will be submitted for presentation at an upcoming medical conference. Additionally, Natera intends to finalize its premarket approval application to the FDA, seeking approval of Signatera as a companion diagnostic for the selection of patients with MIBC to be treated with atezolizumab after cystectomy.

“The results of IMvigor011 are very 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, of Barts Cancer Centre at St Bartholomew’s Hospital in London, England, and lead principal investigator of the study, stated in a news release. “We look forward to presenting the positive results later this year.”

Previously reported data from IMvigor011 demonstrated that among 171 patients who remained MRD-negative using the Signatera assay during the surveillance window experienced 12- and 18-month OS rates of 100% and 98% respectively; the respective 12- and 18-month DFS rates were 92% and 88%.

“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, added in the news release.

IMvigor011 Background

The double-blind, multicenter, randomized, placebo-controlled phase 3 study enrolled patients 18 years and older with histologically confirmed MIBC who underwent surgical resection.2 patients who received neoadjuvant chemotherapy needed to have a tumor stage of ypT2-4a or ypN+ and M0, and those without prior neoadjuvant chemotherapy could have a tumor stage of pT2-4a or pN+ and M0. Patients who had not received prior platinum-based neoadjuvant chemotherapy needed to be ineligible for cisplatin-based adjuvant therapy, refused it, or did not receive it based on physician decision.

Patients needed to be free from residual disease and metastases, based on imaging completed no more than 4 weeks prior to enrollment. Full recovery from cystectomy and enrollment within 24 weeks after surgery was required, although a minimum of 6 weeks was needed to pass from surgery.

To be included in the treatment portion of the study, patients needed to be circulating tumor DNA (ctDNA) positive. They were also required to have an ECOG performance status of 2 or lower, a life expectancy of at least 12 weeks, and adequate hematologic and end-organ function.

Key exclusion criteria for the treatment phase included the receipt of any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks of randomization, or any treatment with adjuvant chemotherapy or radiation therapy following cystectomy.

Patients who tested positive for ctDNA during the 12 months following surgery were randomly assigned to receive atezolizumab at 1680 mg or placebo on day 1 of each 28-day cycle for 12 cycles or up to 1 year. Patients who remained ctDNA-negative for 12 months remained in surveillance and entered study follow-up.

DFS served as the trial’s primary end point. Secondary end points included OS, disease-specific survival, distant metastasis–free survival, quality of life, ctDNA clearance, and safety.

References

1. IMvigor011 bladder cancer trial achieves positive results, with Signatera strongly predicting adjuvant immunotherapy benefit. News release. Natera. 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. Updated June 22, 2025. Accessed August 18, 2025. https://clinicaltrials.gov/study/NCT04660344