FDA approves atezolizumab as adjuvant therapy for MIBC guided by ctDNA

The FDA approved atezolizumab (Tecentriq) and atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) as adjuvant treatments for adults 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.

The agency simultaneously approved the Signatera CDx as a companion diagnostic to identify patients with ctDNA MRD who are eligible for treatment.

The decision caps a years-long scientific journey that began with a failed unselected trial, pivoted through retrospective biomarker analysis, and ultimately yielded a positive prospective phase 3 study—IMvigor011 (NCT04660344)—that demonstrated statistically significant improvements in both disease-free survival (DFS) and overall survival (OS).

From IMvigor010 to IMvigor011

The approval builds directly on lessons learned from the phase 3 IMvigor010 trial (NCT02450331), which evaluated adjuvant atezolizumab in unselected patients with MIBC following cystectomy. That trial did not demonstrate a significant DFS or OS benefit.

Investigators, however, did not abandon the hypothesis that atezolizumab could benefit high-risk patients after surgery. Instead, they conducted a retrospective ctDNA analysis of the IMvigor010 cohort. Approximately 40% of patients were identified as ctDNA positive using the Signatera assay, a tumor-informed approach. Among those ctDNA-positive patients who had received atezolizumab, an exploratory analysis showed an HR o of 0.59 for OS compared with placebo. The ctDNA-negative patients, by contrast, showed no meaningful benefit, with an HR of 1.38, and demonstrated markedly lower rates of relapse (roughly 30% vs 90% in ctDNA-positive patients).

"We did what we said we would do. It was a huge undertaking, and it resulted in a progression-free and an overall survival advantage," said Thomas B. Powles, MBBS, MRCP, MD, professor of genitourinary oncology and director of the Barts Cancer Centre at St. Bartholomew's Hospital in London, who presented the IMvigor011 data at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin.

That retrospective work formed the scientific rationale for IMvigor011—a prospective, randomized, double-blind, placebo-controlled phase 3 trial designed to confirm whether ctDNA could serve as a biomarker to guide adjuvant immunotherapy decisions.

IMvigor011 trial design

IMvigor011 (NCT04660344) enrolled patients with MIBC who were within 6 to 24 weeks of radical cystectomy with lymph node dissection, had histologically confirmed (y)pT2-T4aN0M0 or (y)pT0-T4aN+M0 urothelial cancer, no evidence of radiographic disease, and ECOG performance status 0 to 2. Prior neoadjuvant chemotherapy was permitted.

Investigators performed serial ctDNA surveillance using the Signatera assay beginning at least 6 weeks after cystectomy and continuing for up to 12 months. Patients who tested ctDNA positive at any point and had no evidence of radiographic disease were eligible for randomization. A total of 379 patients tested ctDNA positive at any point during the monitoring period; 250 were ultimately randomly assigned and considered efficacy evaluable.

Randomization was 2:1: 167 patients were assigned to receive atezolizumab 1680 mg intravenously every 4 weeks for up to 12 cycles or 1 year, and 83 were assigned to placebo on the same schedule. Treatment continued until disease recurrence, unacceptable toxicity, or completion of the treatment period.

An additional 377 patients remained persistently ctDNA negative throughout the monitoring period and received no treatment, instead undergoing ongoing surveillance—providing a real-world reference cohort.

Efficacy: Significant gains in DFS and OS

At a median follow-up of 16.1 months, IMvigor011 met its primary end point. Atezolizumab demonstrated a statistically significant improvement in investigator-assessed DFS compared with placebo among ctDNA-positive patients.

Median DFS was 9.9 months (95% CI: 7.2–12.7) in the atezolizumab group vs 4.8 months (95% CI: 4.1–8.3) in the placebo group (stratified hazard ratio [HR] 0.64 [95% CI: 0.47–0.87]; P = .0047).

A statistically significant OS benefit was also observed, with a median OS of 32.8 months (95% CI: 27.7–not estimable [NE]) in the atezolizumab arm vs 21.1 months (95% CI: 14.7–NE) in the placebo arm (HR 0.59 [95% CI: 0.39–0.90]; P = .0131)—representing a 41% reduction in the risk of death.

The trial also reported data by timing of ctDNA positivity. In patients who were ctDNA positive at baseline, median DFS was 8.3 months in the atezolizumab group versus 4.2 months with placebo (HR 0.62 [95% CI: 0.42–0.91]). In those who became ctDNA positive at a subsequent assessment, median DFS was 10.5 months versus 8.3 months (HR 0.66 [95% CI: 0.40–1.10]).

Powles highlighted additional findings regarding ctDNA clearance, which occurred in 25.1% of atezolizumab-treated patients versus 14.5% of placebo-treated patients—suggesting a biological signal consistent with immunologic disease control.

Patients who were persistently ctDNA negative throughout the surveillance period demonstrated excellent outcomes without any treatment: a 24-month DFS rate of 88.4% and a 24-month OS rate of 97.1%. This underscores the potential of ctDNA testing to spare low-risk patients from unnecessary therapy.

Safety profile consistent with known atezolizumab data

The safety profile of atezolizumab in IMvigor011 was consistent with its established profile in prior trials. Grade 3 or 4 treatment-related adverse events occurred in 7.3% of patients in the atezolizumab arm (12 of 167 safety-evaluable patients) compared with 3.6% in the placebo arm (3 of 83 patients).

"The adverse event profile is what you would expect for atezolizumab," Powles remarked at ESMO 2025.

Signatera CDx approved alongside atezolizumab

Central to the approval is the simultaneous clearance of the Signatera CDx as a companion diagnostic. This assay uses a tumor-informed, personalized approach to detect ctDNA MRD in blood samples taken serially after cystectomy.

Clinicians should note that the approval specifically requires the use of an FDA-authorized test to determine ctDNA MRD status before initiating adjuvant atezolizumab. The Signatera CDx is currently the only such authorized companion diagnostic for this indication.

DISCLOSURES

Powles reported disclosures from Astellas, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Eli Lilly, Exelixis, F. Hoffmann-La Roche Ltd, Foundation Medicine Inc, Genentech Inc, Gilead, GlaxoSmithKline, Ipsen, Janssen, Johnson & Johnson, Merck-Serono, Merck Sharp & Dohme, Natera, Novartis, Pfizer, and Seagen.

REFERENCES

1. US Food and Drug Administration. FDA approval of atezolizumab (Tecentriq) and atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) for adjuvant treatment of MIBC. May 15, 2026. Accessed May 15, 2026. https://tinyurl.com/msrrrt9u

1. Powles T, Kann AG, Castellano D, et al. IMvigor011: A phase III trial of circulating tumour (ct)DNA-guided adjuvant atezolizumab vs placebo in muscle-invasive bladder cancer. Presented at: European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. LBA8.

2. Powles T, Kann AG, Castellano D, et al. ctDNA-guided adjuvant atezolizumab in muscle-invasive bladder cancer. N Engl J Med. Published online October 20, 2025. doi:10.1056/NEJMoa2511885.

3. Bellmunt J, Hussain M, Gschwend JE, et al. Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010). Lancet Oncol. 2021;22(4):525-537. doi:10.1016/S1470-2045(21)00004-8.

4. Powles T, Assaf ZJ, Davarpanah N, et al. ctDNA guiding adjuvant immunotherapy in urothelial carcinoma. Nature. 2021;595(7867):432-437. doi:10.1038/s41586-021-03642-9.

5. Updated overall survival by circulating tumor DNA status from the phase 3 IMvigor010 trial. Eur Urol. 2024;85(2):114-122. doi:10.1016/j.eururo.2023.06.007.