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

NCT04660344 | Active Not Recruiting Phase 3 FDA Drug

• 3 other identifiers: BO428432020-004418-362022-502705-15-00
• Study Type: interventional
• Target: 761
• Locations: 24 countries
• Sites: 148

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.

Conditions

Muscle-invasive Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• Investigator-assessed (INV) - Disease-free Survival (DFS)

  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.

  Randomization up to first occurrence of DFS event (up to approximately 49 months)

Secondary Outcomes (10)

• Overall survival (OS)

  Randomization up to death from any cause (up to approximately 6 years)

• Independent Review Facility (IRF)-assessed DFS

  Randomization up to first occurrence of DFS event (up to approximately 49 months)

• INV Disease-specific Survival (DSS)

  Randomization to death from UC (up to approximately 6 years)

• INV Distant Metastasis-free Survival (DMFS)

  Randomization to diagnosis of distant metastases or death from any cause (up to approximately 49 months)

• Time to Confirmed Deterioration of Function and Health-related Quality of Life (HRQoL)

  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)

Study Arms (3)

Arm A: Atezolizumab

EXPERIMENTAL

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.

Drug: Atezolizumab; Device: Signatera

Arm B: Placebo

PLACEBO COMPARATOR

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.

Other: Placebo; Device: Signatera

Arm C: Surveillance Follow-Up

EXPERIMENTAL

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.

Device: Signatera

Interventions

Atezolizumab DRUG

ctDNA positive participants will receive 1680 mg IV, every 4 weeks (Q4W) on Day 1 of each 28-day cycle.

Also known as: Tecentriq

Arm A: Atezolizumab

Placebo OTHER

ctDNA positive participants will receive placebo IV, Q4W on Day 1 of each 28-day cycle

Arm B: Placebo

Signatera DEVICE

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.

Arm A: Atezolizumab; Arm B: Placebo; Arm C: Surveillance Follow-Up

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Natera, Inc.: collaborator

Study Sites (148)

Cancer Care Centers of Brevard

Rockledge, Florida, 32955, United States

Location

Optum Health Care

Las Vegas, Nevada, 89102, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

AHN Cancer Institute ? Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Centro Medico Austral

Buenos Aires, 1019, Argentina

Location

Instituto Alexander Fleming

Buenos Aires, 1426, Argentina

Location

AZ KLINA

Brasschaat, 2930, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Oncocentro Serviços Medicos E Hospitalares Ltda

Fortaleza, Ceará, 60170-170, Brazil

Location

CETUS Hospital Dia Oncologia

Belo Horizonte, Minas Gerais, 30110022, Brazil

Location

Hospital Erasto Gaertner

Curitiba, Paraná, 81520-060, Brazil

Location

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, 90035-001, Brazil

Location

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Hospital Nossa Senhora da Conceicao

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

Location

*X*Fundação Pio XII Hospital de Câncer de Barretos

Barretos, São Paulo, 14784-400, Brazil

Location

Hospital Amaral Carvalho

Jaú, São Paulo, 17210-120, Brazil

Location

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, 01246-000, Brazil

Location

Hospital Alemao Oswaldo Cruz

São Paulo, São Paulo, 01323-020, Brazil

Location

Friendship Hospital, Capital Medical University

Beijing, 100050, China

Location

the First Hospital of Jilin University

Changchun, 130021, China

Location

Hu Nan Provincial Cancer Hospital

Changsha, 410006, China

Location

Chongqing Cancer Hospital

Chongqing, 400030, China

Location

The First Affiliated Hospital of Fujian Medical University

Fuzhou, 350005, China

Location

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, 510120, China

Location

Jiangsu Cancer Hospital

Nanjing, 210009, China

Location

Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)

Nanjing, 210029, China

Location

Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School

Nanjing, 210029, China

Location

Zhongshan Hospital Fudan University

Shanghai, 200032, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200120, China

Location

Tianjin Cancer Hospital

Tianjin, 300060, China

Location

Yantai Yu Huangding Hospital

Yantai, 264099, China

Location

Clinica del Country

Bogotá, 11001, Colombia

Location

Instituto Cancerología Medellin

Medellín, 050024, Colombia

Location

Oncomedica S.A.

Montería, 230002, Colombia

Location

Fakultni nemocnice Olomouc

Olomouc, 779 00, Czechia

Location

Fakultni nemocnice v Motole

Prague, 150 06, Czechia

Location

Fakultni Thomayerova nemocnice

Praha 4 - Krc, 140 59, Czechia

Location

ICO Paul Papin

Angers, 49055, France

Location

Institut Sainte Catherine

Avignon, 84918, France

Location

Hopital Saint Andre

Bordeaux, 33075, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Centre D'Oncologie de Gentilly

Nancy, 54100, France

Location

Institut Mutualiste Montsouris

Paris, 75674, France

Location

Hopital Foch

Suresnes, 92151, France

Location

Institut Claudius Régaud

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

Krankenhaus Martha-Maria Halle-Dölau, Klinik für Urologie

Halle, 06120, Germany

Location

Universitätsklinikum der Ruhr-Universität Bochum, Marien-Hospital Herne, Urologische Klinik

Herne, 44625, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

Attikon University General Hospital

Ahens, 124 64, Greece

Location

Alexandras General Hospital of Athens

Athens, 115 28, Greece

Location

University Hospital of Larissa

Larissa, 411 10, Greece

Location

University Hospital of Patras Medical Oncology

Pátrai, 265 04, Greece

Location

Theageneio Hospital

Thessaloniki, 54007, Greece

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Cork Uni Hospital

Cork, Ireland

Location

Adelaide & Meath Hospital, Dublin, Incorporating the National Children's Hospital

Dublin, D24 NR0A, Ireland

Location

Tel Aviv Sourasky Medical Ctr

Tel Aviv, 6423906, Israel

Location

Azienda Ospedaliera di Rilievo Nazionale "Antonio Cardarelli", Day Hospital Oncologico

Naples, Campania, 80131, Italy

Location

Istituto Nazionale Tumori Irccs Fondazione G. Pascale

Naples, Campania, 80131, Italy

Location

AZ.Osp S. Orsola ? Malpighi-Reparto di Oncologia Medica

Bologna, Emilia-Romagna, 40138, Italy

Location

IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola

Meldola, Emilia-Romagna, 47014, Italy

Location

Policlinico Universitario "Agostino Gemelli"

Rome, Lazio, 00168, Italy

Location

A.O. Universitaria S. Martino Di Genova

Genoa, Liguria, 16132, Italy

Location

Irccs Ospedale San Raffaele

Milan, Lombardy, 20132, Italy

Location

Irccs Istituto Nazionale Dei Tumori (Int)

Milan, Lombardy, 20133, Italy

Location

Istituto Europeo Di Oncologia

Milan, Lombardy, 20141, Italy

Location

A.O. Universitaria S. Luigi Gonzaga

Orbassano, Piedmont, 10043, Italy

Location

Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato

Arezzo, Tuscany, 52100, Italy

Location

Azienda Ospedaliera Santa Maria di Terni

Terni, Umbria, 20089, Italy

Location

IOV - Istituto Oncologico Veneto - IRCCS

Padua, Veneto, 35128, Italy

Location

Nagoya University Hospital

Aichi, 466-8560, Japan

Location

Chiba Cancer Center

Chiba, 260-8717, Japan

Location

Toho University Sakura Medical Center

Chiba, 285-8741, Japan

Location

Shikoku Cancer Center

Ehime, 791-0280, Japan

Location

Fukuyama City Hospital

Hiroshima, 721-8511, Japan

Location

Hiroshima City Hiroshima Citizens Hospital

Hiroshima, 730-8518, Japan

Location

National Hospital Organization Hokkaido Cancer Center

Hokkaido, 003-0804, Japan

Location

University of Tsukuba Hospital

Ibaraki, 305-8576, Japan

Location

St. Marianna University Hospital

Kanagawa, 216-8511, Japan

Location

Yokosuka Kyosai Hospital

Kanagawa, 238-8558, Japan

Location

Kyoto University Hospital

Kyoto, 606-8507, Japan

Location

Nagano Municipal Hospital

Nagano, 381-8551, Japan

Location

Iwate Medical University Hospital

Numakunai, 028-3695, Japan

Location

Osaka International Cancer Institute

Osaka, 541-8567, Japan

Location

Saitama Medical University International Medical Center

Saitama, 350-1298, Japan

Location

Saitama Cancer Center

Saitama, 362-0806, Japan

Location

Shizuoka Cancer Center

Shizuoka, 411-8777, Japan

Location

National Cancer Center Hospital

Tokyo, 104-0045, Japan

Location

Keio University Hospital

Tokyo, 160-8582, Japan

Location

Toyama University Hospital

Toyama, 930-0194, Japan

Location

CUAN Hospital

San Pedro Garza García, Nuevo León, 66278, Mexico

Location

PRATIA MCM Kraków

Krakow, 30-727, Poland

Location

Szpital Kliniczny im. Heliodora ?wi?cickiego UM w Poznaniu

Poznan, 60-569, Poland

Location

Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.

Warsaw, 04-073, Poland

Location

Dolnoslaskie Centrum Onkologii

Wroclaw, Poland

Location

St-Petersburg Regional Oncology Dispensary

Kuzmolovo, Leningrad, 188663, Russia

Location

Privolzhsk Regional Medical Center

Nizhny Novgorod, Niznij Novgorod, 603001, Russia

Location

FSI Russian Centre of Radiology and Surgical Technologies

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

Ivanovo Regional Oncology Dispensary

Ivanovo, 153040, Russia

Location

National Cancer Centre

Singapore, 168583, Singapore

Location

National Cancer Center

Goyang-si, 10408, South Korea

Location

Samsung Medical Center

Seoul, (0)6351, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Corporacio Sanitaria Parc Tauli

Sabadell, Barcelona, 08208, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, Cordoba, 14004, Spain

Location

Hospital de Donostia

Donostia / San Sebastian, Guipuzcoa, 20080, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic i Provincial

Barcelona, 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Instituto Valenciano Oncologia

Valencia, 46009, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital

Adana, 01230, Turkey (Türkiye)

Location

Ankara University Faculty of Medicine Cebeci Hospital

Ankara, 06700, Turkey (Türkiye)

Location

Ankara City Hospital

Ankara, 06800, Turkey (Türkiye)

Location

Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji

Bakirkoy / Istanbul, 34147, Turkey (Türkiye)

Location

Medikal Park Izmir Hospital

Cordaleo, 35575, Turkey (Türkiye)

Location

Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi

Edirne, 22030, Turkey (Türkiye)

Location

Istanbul University Cerrahpasa Faculty of Medicine

Istanbul, 34098, Turkey (Türkiye)

Location

Medeniyet University Goztepe Training and Research Hospital.

Istanbul, 34730, Turkey (Türkiye)

Location

Medikal Park Samsun

Samsun, 55200, Turkey (Türkiye)

Location

Regional Clinical Center of Urology and Nephrology n.a. V.I. Shapoval Department of Urology #4

Kharkiv, Kharkiv Governorate, 61037, Ukraine

Location

ME Dnipropetrovsk Regional Clinical Hospital n.a. I.I Mechnykov Dnipropetrovsk Regional Council

Dnipro, KIEV Governorate, 49005, Ukraine

Location

Lviv Regional Clinical Hospital

Lviv, KIEV Governorate, 79010, Ukraine

Location

CI Dnipropetrovsk CMCH #4 of Dnipropetrovsk RC SI Dnipropetrovsk MA of MOHU Ch of Oncology and MR

Dnipropetrovsk, 49102, Ukraine

Location

Kyiv City Clinical Oncological Center

Kyiv, 03115, Ukraine

Location

Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Barts Hospital

London, EC1M 6BQ, United Kingdom

Location

University College London NHS Foundation Trust

London, NW1 2PG, United Kingdom

Location

Royal Marsden Hospital - London

London, SW3 6JJ, United Kingdom

Location

Charing Cross Hospital

London, W6 8RF, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Royal Preston Hospital

Preston, PR2 9HT, United Kingdom

Location

Weston Park Hospital

Sheffield, S10 2SJ, United Kingdom

Location

Southampton University Hospitals NHS Trust

Southampton, SO16 6YD, United Kingdom

Location

Royal Marsden Hospital (Sutton)

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (2)

• 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 DERIVED

• 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 DERIVED

MeSH Terms

Interventions

atezolizumab

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Following the primary analysis, the Sponsor has been unblinded, and the investigators can now be unblinded upon request to guide treatment decisions.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2020
• First Posted: December 9, 2020
• Study Start: May 3, 2021
• Primary Completion: June 15, 2025
• Study Completion (Estimated): October 1, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

SG (1); PL (4); BR (10); UA (5); HK (1); ES (14); TU (9); IL (1); CZ (3); DE (6); BE (2); KR (4); IE (2); GR (5); CO (3); CN (13); ME (1); AR (2); US (4); IT (13); JP (20); RU (4); GB (11); FR (10)