FDA Approves Adjuvant Atezolizumab for MRD+ Muscle-Invasive Bladder Cancer

The FDA has approved atezolizumab (Tecentriq) and atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza; subcutaneous atezolizumab) as adjuvant treatments for adult patients with muscle-invasive bladder cancer (MIBC) after cystectomy who have circulating tumor DNA molecular residual disease (ctDNA MRD), as determined by an FDA-authorized test.

In tandem, the FDA approved Signatera CDx as a companion diagnostic device to select patients with MIBC after cystectomy who have ctDNA MRD for adjuvant treatment with atezolizumab or subcutaneous atezolizumab.

The regulatory decision was backed by data from the phase 3 IMvigor011 (NCT04660344), which showed that patients treated with adjuvant atezolizumab achieved a median disease-free survival (DFS) of 9.9 months (95% CI, 7.2-12.7) compared with 4.8 months (95% CI, 4.1-8.3) for those given placebo (HR, 0.64; 95% CI, 0.47-0.87; P = .0047).

Furthermore, atezolizumab generated a median overall survival (OS) of 32.8 months (95% CI, 27.7-not estimable [NE]) vs 21.1 months (95% CI, 14.7-NE) for placebo (HR, 0.59; 95% CI, 0.39-0.90; P = .0131).

"For the patients and families, the 'watch and wait' period after a cystectomy is often defined by uncertainty. This ctDNA-guided approach can enable doctors to use serial ctDNA MRD testing to identify who is at a higher risk of recurrence and move quickly toward immunotherapy for those who may benefit from it, while allowing others to safely avoid additional treatment and its associated [adverse] effects [AEs]," Meri-Margaret Deoudes, chief executive officer of the Bladder Cancer Advocacy Network, stated in a news release.²

How was the IMvigor11 trial conducted?

The global, randomized phase 3 study enrolled patients with MIBC who underwent radical cystectomy within 6 to 24 weeks of screening.³ They needed to have histologically confirmed (y)pT2-T4aN0M0 or (y_pT0-T4aN+M0 urothelial cancer with no evidence of radiographic disease. An ECOG performance status of 0 to 2 was required, and prior neoadjuvant chemotherapy was allowed.

Eligible patients then underwent ctDNA monitoring for up to 1 year following cystectomy. Patients who remained ctDNA negative during that year did not receive any treatment, and they were followed for surveillance.

Patients who had any positive ctDNA test within the first year of surveillance were randomly assigned in a 2:1 fashion to receive intravenous atezolizumab at 1680 mg or placebo once every 4 weeks for up to 1 year.

Investigator-assessed DFS served as the trial’s primary end point. OS was a key secondary end point.

What additional data were reported from the primary analysis of IMvigor11?

Findings presented at the 2025 ESMO Congress showed that among patients who were ctDNA positive at baseline, atezolizumab (n = 167) led to ctDNA clearance at cycle 3 or cycle 5 in 25.1% of patients compared with 14.5% for placebo (n = 83; difference, 10.7%; 95% CI, –0.2% to 21.5%).

Regarding safety, any-grade adverse effects (AEs) occurred in 83.6% of patients treated with atezolizumab (n = 165) compared with 85.5% of patients treated with placebo (n = 83). The rates of any-grade treatment-related AEs (TRAEs) were 49.1% and 50.6%, respectively.

Grade 3/4 AEs were reported in 28.5% of patients in the atezolizumab arm vs 21.7% of patients in the placebo arm; the respective rates of grade 3/4 TRAEs were 7.3% and 2.4%. AEs led to death in 3.0% of patients in the atezolizumab arm vs 2.4% of patients in the placebo arm. The rates of TRAEs leading to death were 1.8% and 0%, respectively.

AEs led to atezolizumab treatment discontinuation in 9.1% of patients and treatment interruption in 23.6% of patients. These respective rates were 3.6% and 19.3% for placebo.

Immune-mediated AEs were reported in 38.8% of patients treated with atezolizumab vs 12.0% of patients treated with placebo. The rates of grade 3/4 immune-mediated AEs were 4.8% and 1.2%, respectively. Immune-mediated AEs led to death in 1 patient in the atezolizumab arm (0.6%) vs no patients in the placebo arm.

What is the recommended dosing for adjuvant atezolizumab in MRD-positive MIBC?

IV atezolizumab is recommended at doses of 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity.¹ Subcutaneous atezolizumab is recommended as 1875 mg of atezolizumab plus 30,000 units of hyaluronidase given once every 3 weeks for up to 1 year or until disease recurrence or unacceptable toxicity.

For patients negative for ctDNA MRD via Signatera CDx following surgery, serial testing should continue until a positive test or the completion of the recommended 1-year testing window.

Hear exclusive insights on the significance of this approval from Jason Hafron, MD, of the Michigan Institute of Urology, in the video below.

References

1. FDA approves atezolizumab for adjuvant treatment of muscle invasive bladder cancer in patients with molecular residual disease. FDA. May 15, 2026. Accessed May 15, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-atezolizumab-adjuvant-treatment-muscle-invasive-bladder-cancer-patients-molecular
2. FDA approves Genentech’s Tecentriq for adjuvant muscle-invasive bladder cancer with ctDNA-guided treatment. News release. Genentech. May 15, 2026. Accessed May 15, 2026. https://www.gene.com/media/press-releases/15112/2026-05-15/fda-approves-genentechs-tecentriq-for-ad
3. Powles T, Kann AG, Castellano D, et al. IMvigor011: a phase 3 trial of circulating tumour (ct)DNA-guided adjuvant atezolizumab vs placebo in muscle-invasive bladder cancer. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA8.