TriangleNCT04660344 · CITED IN SOURCE DOCUMENTS
A Study of Atezolizumab Versus Placebo as Adjuvant Therapy in Participants With High-risk Muscle-invasive Bladder Cancer (MIBC) Who Are ctDNA Positive Following Cystectomy
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2026-03-27
This is a global Phase III, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy and safety of adjuvant treatment with atezolizumab compared with placebo in participants with MIBC who are circulating tumour deoxyribonucleic acid (ctDNA) positive and are at high risk for recurrence following cystectomy.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
No posted result sections were captured. Registered plans do not establish that a treatment works.
Who could take part
- eligibility Criteria
- Inclusion Criteria: Inclusion Criteria for the Surveillance Phase: * Histologically confirmed MIUC (also termed transitional cell carcinoma \[TCC\]) of the bladder * Tumor, nodes, and metastases (TNM) classification (based on American Joint Committee on Cancer \[AJCC\] Cancer Staging Manual, 8th Edition; Amin et al. 2016) at pathological examination of surgical resection specimen as follows: For participants treated with prior neoadjuvant chemotherapy (NAC): tumor stage of ypT2-4a or ypN+ and M0. For participants who have not received prior NAC: tumor stage of pT2-4a or pN+ and M0 * Surgical resection of MIUC of the bladder * Participants who have not received prior platinum-based NAC must be ineligible for cisplatin-based adjuvant chemotherapy, have refused it, or will not receive it based on physician's decision * ctDNA assay developed based on tumor tissue specimen and matched normal DNA from blood * Tumor programmed death ligand (PD-L1) expression per immunohistochemistry (IHC) that is evaluable by central testing of a representative tumor tissue specimen * Absence of residual disease and absence of metastasis, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan of the pelvis, abdomen, and chest no more than 4 weeks prior to enrollment * Full recovery from cystectomy and enrollment within 24 weeks following cystectomy. Minimum of 6 weeks must have elapsed from surgery Additional Inclusion Criteria for the Treatment Phase: * Blood for plasma ctDNA sample evaluated to be ctDNA positive, defined as the presence of two or more mutations out of the 16 mutations identified based on participant' whole exome sequencing (WES) evaluable (ctDNA assay designability) report * Absence of residual disease and absence of metastasis, as confirmed by a negative baseline CT or MRI scan of the pelvis, abdomen, and chest no more than 28 days prior to randomization, as assessed by the investigator and Independent Review Facility * Eastern cooperative oncology group (ECOG) performance status of ≤ 2 * Life expectancy ≥12 weeks * Adequate hematologic and end-organ function * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs Exclusion Criteria: General Medical Exclusion Criteria for the Surveillance Phase: * Known PD-L1 IHC result for adjuvant therapy. The decision for the adjuvant therapy should not be based on the PD-L1 IHC result * Pregnancy or breastfeeding * Positive test for human immunodeficiency virus (HIV), with the following exception: Participants with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy, have a cluster of differentiation 4 (CD4) count ≥ 200 per microliter (/µL), and have an undetectable viral load * Participants with active hepatitis B virus (HBV) or hepatitis C virus (HCV). Participants with past HBV infection or resolved HBV infection are eligible. A negative HBV deoxyribonucleic acid (DNA) test must be obtained in these participants prior to enrollment. Participants positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA * Active tuberculosis (TB) confirmed by a test performed within 3 months prior to treatment initiation * History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins * Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation * History of autoimmune disease. Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. Participants with controlled type I diabetes mellitus (T1DM) on a stable dose of insulin regimen may be eligible for this study * History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted * Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction (MI) within the previous 3 months, unstable arrhythmias, or unstable angina Cancer-Specific Exclusion Criteria for the Surveillance Phase: * Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to study enrollment * Adjuvant chemotherapy or radiation therapy for UC following cystectomy * Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or 5 half-lives of the drug, whichever is longer, prior to enrollment * Malignancies other than UC within 5 years prior to study enrollment Additional Exclusion Criteria for the Treatment Phase: * Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to randomization to the treatment phase. Hormone-replacement therapy or oral contraceptives are allowed * Adjuvant chemotherapy or radiation therapy for UC following cystectomy * Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or 5 half-lives of the drug, whichever is longer, prior to randomization to the treatment phase * Positive test for HIV, with the following exception: Participants with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy, have a CD4 count ≥200/μL, and have an undetectable viral load * Participants with active HBV or HCV * Active tuberculosis confirmed by a test performed within 3 months prior to treatment initiation
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Atezolizumab will be administered intravenously (IV) at a dose of 1680 milligrams (mg) on Day 1 of each 28-day cycle for 12 cycles or up to 1 year (whichever occurs first). Atezolizumab will be discontinued in the event of disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination by the Sponsor.
- intervention Names
- Drug: Atezolizumab
- Device: Signatera
- label
- Arm A: Atezolizumab
- type
- EXPERIMENTAL
- description
- Placebo will be administered IV on Day 1 of each 28-day cycle. Placebo will be discontinued in the event of disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination by the Sponsor. Following the primary analysis, participants randomized to the comparator arm might discontinue placebo and may receive treatment outside the study at the investigator's discretion.
- intervention Names
- Other: Placebo
- Device: Signatera
- label
- Arm B: Placebo
- type
- PLACEBO_COMPARATOR
- description
- Participants who remain ctDNA negative at 12 months from the date of cystectomy will not be randomized to treatment and will enter surveillance follow-up.
- intervention Names
- Device: Signatera
- label
- Arm C: Surveillance Follow-Up
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Arm A: Atezolizumab
- description
- ctDNA positive participants will receive 1680 mg IV, every 4 weeks (Q4W) on Day 1 of each 28-day cycle.
- name
- Atezolizumab
- other Names
- Tecentriq
- type
- DRUG
- arm Group Labels
- Arm B: Placebo
- description
- ctDNA positive participants will receive placebo IV, Q4W on Day 1 of each 28-day cycle
- name
- Placebo
- type
- OTHER
- arm Group Labels
- Arm A: Atezolizumab
- Arm B: Placebo
- Arm C: Surveillance Follow-Up
- description
- Signatera will be used to evaluate whether ctDNA is detected during serial monitoring of peripheral blood samples for participants enrolled in surveillance. Participants with a ctDNA positive result will be screened for inclusion in the treatment phase. Participants who remain ctDNA negative at 12 months from the date of cystectomy will not be randomized to treatment and will enter surveillance follow-up.
- name
- Signatera
- type
- DEVICE
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- DOUBLE
- masking Description
- Following the primary analysis, the Sponsor has been unblinded, and the investigators can now be unblinded upon request to guide treatment decisions.
- who Masked
- PARTICIPANT
- INVESTIGATOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 761
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- INV-DFS, defined as the time from randomization to the first occurrence of a DFS event, defined as any of the following: * Local (pelvic) recurrence of urothelial carcinoma (UC) (including soft tissue and regional lymph nodes); * Urinary tract recurrence of UC (including all pathological stages and grades); * Distant metastasis of UC; * Death from any cause.
- measure
- Investigator-assessed (INV) - Disease-free Survival (DFS)
- time Frame
- Randomization up to first occurrence of DFS event (up to approximately 49 months)
- secondary Outcomes
- description
- OS, defined as the time from randomization to death from any cause.
- measure
- Overall survival (OS)
- time Frame
- Randomization up to death from any cause (up to approximately 6 years)
- measure
- Independent Review Facility (IRF)-assessed DFS
- time Frame
- Randomization up to first occurrence of DFS event (up to approximately 49 months)
- description
- INV-DSS, defined as the time from randomization to death from UC per investigator assessment of cause of death.
- measure
- INV Disease-specific Survival (DSS)
- time Frame
- Randomization to death from UC (up to approximately 6 years)
- description
- INV-DMFS, defined as the time from randomization to the diagnosis of distant (i.e., non-locoregional) metastases or death from any cause.
- measure
- INV Distant Metastasis-free Survival (DMFS)
- time Frame
- Randomization to diagnosis of distant metastases or death from any cause (up to approximately 49 months)
- description
- Time to confirmed deterioration of function and HRQoL, defined as the time from randomization to the date of a participant's first score decrease of ≥ 10 points from baseline on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) physical function scale, role function scale, and the global health status (GHS)/QoL scale (separately), held for at least two consecutive time points or followed by death.
- measure
- Time to Confirmed Deterioration of Function and Health-related Quality of Life (HRQoL)
- time Frame
- Randomization to participant's first score decrease of ≥ 10 points from baseline on EORTC QLQ-C30 physical function scale, role function scale, and the GHS/QoL Scale (up to approximately 49 months)
- description
- ctDNA clearance, defined as the proportion of participants who are ctDNA positive at baseline and ctDNA negative at Cycle 3, Day 1 or Cycle 5, Day 1.
- measure
- ctDNA Clearance
- time Frame
- Baseline, Cycle 3 Day 1 or Cycle 5 Day 1 (each cycle is 28 days)
- measure
- Percentage of Participants With Adverse Events (AEs)
- time Frame
- Baseline up to approximately 6 years
- measure
- Serum Concentration of Atezolizumab
- time Frame
- At pre-defined intervals from first administration of study drug (up to approximately 49 months)
- description
- Incidence of ADAs to atezolizumab after initiation of study treatment (postbaseline incidence).
- measure
- Incidence of Anti-Drug Antibodies (ADAs) to Atezolizumab
- time Frame
- Baseline up to approximately 49 months
- description
- Prevalence of ADAs to atezolizumab at baseline.
- measure
- Prevalence of ADAs to Atezolizumab
- time Frame
- Baseline
Full study description
- brief Summary
- This is a global Phase III, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy and safety of adjuvant treatment with atezolizumab compared with placebo in participants with MIBC who are circulating tumour deoxyribonucleic acid (ctDNA) positive and are at high risk for recurrence following cystectomy.
Source references
- references
- citation
- Powles T, Kann AG, Castellano D, Gross-Goupil M, Nishiyama H, Bracarda S, Bjerggaard Jensen J, Makaroff L, Jiang S, Ku JH, Park SH, Reig Torras O, Ye D, Maruzzo M, Necchi A, Morales-Barrera R, Giunta EF, Lee JL, Tortora G, Urun Y, Dolowy L, Erdem D, Pinto A, Grando F, Zou W, Assaf ZJ, Vuky J, Degaonkar V, Steinberg EE, Bellmunt J, Gschwend JE; IMvigor011 Investigators. ctDNA-Guided Adjuvant Atezolizumab in Muscle-Invasive Bladder Cancer. N Engl J Med. 2025 Dec 18;393(24):2395-2408. doi: 10.1056/NEJMoa2511885. Epub 2025 Oct 20.
- pmid
- 41124204
- type
- DERIVED
- citation
- Jackson-Spence F, Toms C, O'Mahony LF, Choy J, Flanders L, Szabados B, Powles T. IMvigor011: a study of adjuvant atezolizumab in patients with high-risk MIBC who are ctDNA+ post-surgery. Future Oncol. 2023 Mar;19(7):509-515. doi: 10.2217/fon-2022-0868. Epub 2023 Apr 21.
- pmid
- 37082935
- type
- DERIVED
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Preserved source evidence · Not medical advice