A Study of Atezolizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer (Cohort 1)

A Phase II, Multicenter, Single-Arm Study of Atezolizumab in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer

This Phase II, single-arm study is designed to evaluate the effect of atezolizumab treatment in participants with locally advanced or metastatic urothelial bladder cancer. Participants will be enrolled into 1 of 2 cohorts. Cohort 1 (reported here) will consist of participants who are treatment-naïve and ineligible for cisplatin-containing chemotherapy. Cohort 2 will contain participants who have progressed during or following a prior platinum-based chemotherapy regimen. The results of the second cohort are reported separately (NCT02108652). Participants in both cohorts will be given a 1200 milligrams (mg) intravenous (IV) dose of atezolizumab on Day 1 of 21-day cycles. Treatment of participants in Cohort 1 will continue until disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or unmanageable toxicity. Treatment of participants in Cohort 2 will continue until loss of clinical benefit or unmanageable toxicity.

Study Overview

• Status: Completed
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: Atezolizumab

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 2

Expanded Access

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Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • Bcca - Cancer Center Southern Interior
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA-Vancouver Cancer Centre
  • Ontario
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health Oshawa; Oncology
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Cancer Centre; Oncology
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Odette Cancer Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network; Princess Margaret Hospital; Medical Oncology Dept
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
• France
  • Paris, France, 75475
    • APHP - Hospital Saint Louis
  • Suresnes, France, 92151
    • Hopital Foch; Oncologie
  • Villejuif, France, 94800
    • Institut Gustave Roussy; Oncologie Medicale
• Germany
  • Berlin, Germany, 12200
    • Charité - Universitätsmedizin Berlin; CC 8: Chirurgische Medizin; Klinik für Urologie
  • Düsseldorf, Germany, 40225
    • Universitätsklinikum Düsseldorf; Urologische Klinik
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg; Chirurgische Klinik; Abteilung Urologie
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II
  • München, Germany, 81675
    • Klinikum rechts der Isar der TU München; Urologische Klinik und Poliklinik
• Italy
  • Lombardia
    • Milano, Lombardia, Italy, 20133
      • Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
  • Toscana
    • Arezzo, Toscana, Italy, 52100
      • Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • The Netherlands Cancer Institute - Antoni Van Leeuwenhoekziekenhuis
• Spain
  • Barcelona, Spain, 08908
    • Institut Catala d Oncologia Hospital Duran i Reynals
  • Barcelona, Spain, 08035
    • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Oncologia
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre; Servicio de Oncologia
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio; Servicio de Oncologia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra; Servicio de Oncologia
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • University Hospital Birmingham The Cancer Centre, Queen Elizabeth Hospital
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute
  • London, United Kingdom, EC1M 6BQ
    • Barts and The London
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital; Dept of Medical Oncology
  • Wirral, United Kingdom, L63 4JY
    • The Clatterbridge Cancer Centre NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Pinnacle Oncology Hematology
    • Tucson, Arizona, United States, 85710
      • Arizona Oncology - HOPE Wilmot
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Cancer Center
    • Los Angeles, California, United States, 90024
      • UCLA
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute - W LA Office
    • San Francisco, California, United States, 94143-0106
      • UCSF
    • San Marcos, California, United States, 92069
      • Kaiser Permanente - San Marcos
    • Stanford, California, United States, 94305-5820
      • Stanford Cancer Center
    • Vallejo, California, United States, 94589
      • Kaiser Permanente; Oncology Clinical Trials
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Center - Aurora
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut Health Center
    • New Haven, Connecticut, United States, 06520
      • Yale Cancer Center ; Medical Oncology
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Georgetown University Medical Center Lombardi Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Piedmont Cancer Institute, PC
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago; Hematology/Oncology
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital
  • Indiana
    • Goshen, Indiana, United States, 46526
      • Indiana University Health; Goshen Center for Cancer Care
  • Kentucky
    • Louisville, Kentucky, United States, 40402
      • Norton Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital;Oncology
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Inst. ; Dept. of Medical Oncology
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center, Harvard Medical School; Department of Medicine
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology Minneapolis
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Urology Cancer Center & GU Research Network
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Comprehensive Cancer Centers of Nevada
  • New York
    • Albany, New York, United States, 12208
      • New York Oncology Hematology, P.C.
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine - Tisch Cancer Institute
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care Inc
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve Univ; Hem/Onc
  • Oregon
    • Eugene, Oregon, United States, 97401-8122
      • Willamette Valley Cancer Ctr - 520 Country Club
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Kimmel Cancer Center Thomas Jefferson University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Cancer Center - Tennessee Oncology, Pllc
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Ctr For Cancer And Blood Disorders
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77024
      • Texas Oncology - Houston (Gessner)
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates - Lake Wright Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, urethra)
• Representative tumor specimens as specified by the protocol
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy greater than or equal to (>=) 12 weeks
• Measurable disease, as defined by RECIST v1.1
• Adequate hematologic and end organ function

Cohort 1-Specific Inclusion Criteria

• No prior chemotherapy for inoperable locally advanced or metastatic or recurrent urothelial carcinoma
• Ineligible for cisplatin-based chemotherapy due to one of the following: Impaired renal function, a hearing loss of 25 decibels (dB) at two contiguous frequencies, Grade 2 or greater peripheral neuropathy, or ECOG performance score of 2

Exclusion Criteria:

• Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
• Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
• Leptomeningeal disease
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Uncontrolled hypercalcemia (greater than [>] 1.5 millimoles per liter [mmol/L] ionized calcium or Ca > 12 milligrams per deciliter [mg/dL] or corrected serum calcium > upper limits of normal [ULN]) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
• Malignancies other than urothelial bladder cancer within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome or incidental prostate cancer
• Pregnant and lactating women
• History of autoimmune disease
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• Serum albumin less than (<) 2.5 grams per deciliter (g/dL)
• Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or hepatitis C or tuberculosis
• Severe infections within 4 weeks prior to Cycle 1, Day 1
• Significant cardiovascular disease
• Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1
• Prior allogeneic stem cell or solid organ transplant
• Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4), anti-programmed death-1 receptor (anti-PD-1), and anti-programmed death-ligand 1 (anti-PD-L1) therapeutic antibodies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Treatment-naive Cisplatin Ineligible Participants; Participants with advanced disease who are treatment-naive for advanced urothelial carcinoma and cisplatin ineligible will receive atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.	Drug: Atezolizumab; Atezolizumab 1200 mg will be given by IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.; Other Names: Tecentriq; MPDL3280A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Confirmed Objective Response of Complete Response (CR) or Partial Response (PR) as Assessed by the Independent Review Facility (IRF) According to RECIST v1.1	Tumor response was assessed by the IRF according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as greater than or equal to (≥) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a confirmed objective response of CR or PR was reported. The exact 95% confidence interval (CI) was calculated using the Clopper-Pearson method.	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) as Assessed by the IRF According to RECIST v1.1	DOR was defined as the time from the initial occurrence of documented CR or PR (whichever occurred first) until documented disease progression or death due to any cause on study, whichever occurred first. Tumor response was assessed by the IRF according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR.	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
DOR as Assessed by the Investigator According to RECIST v1.1	DOR was defined as the time from the initial occurrence of documented CR or PR (whichever occurred first) until documented disease progression or death due to any cause on study, whichever occurred first. Tumor response was assessed by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and no new measurable or unmeasurable lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD.	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
Percentage of Participants With Death or Disease Progression as Assessed by the IRF According to RECIST v1.1	Tumor response was assessed by the IRF according to RECIST v1.1. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
Progression-Free Survival (PFS) as Assessed by the IRF According to RECIST v1.1	PFS was defined as the time from start of treatment to the first event of death or PD. Tumor response was assessed by the IRF according to RECIST v1.1. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
Percentage of Participants With Death or Disease Progression as Assessed by the Investigator According to RECIST v1.1	Tumor response was assessed by the investigator according to RECIST v1.1. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The percentage of participants who died or experienced PD was reported.	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
PFS as Assessed by the Investigator According to RECIST v1.1	PFS was defined as the time from start of treatment to the first event of death or PD. Tumor response was assessed by the investigator according to RECIST v1.1. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
Percentage of Participants With a Confirmed Objective Response of CR or PR as Assessed by the Investigator According RECIST v1.1	Tumor response was assessed by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a confirmed objective response of CR or PR was reported. The exact 95% CI was calculated using the Clopper-Pearson method.	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
Percentage of Participants Who Died	The percentage of participants who died from any cause was reported.	Baseline until death (data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
Overall Survival (OS)	OS was defined as the time from start of treatment to the time of death from any cause on study.	Baseline until death (data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
Percentage of Participants Alive at 1-year		1-year
Maximum Serum Concentration (Cmax) of Atezolizumab		Pre-dose (0 hours) and 30 minutes post-dose on Day 1 of Cycle 1 (Cycle length = 21 days)
Minimum Serum Concentration (Cmin) of Atezolizumab		Pre-dose (0 hours) on Day 1 of Cycles 1, 2, 3, 4, 8 (Cycle length = 21 days)
Percentage of Participants Positive for Anti-therapeutic Antibodies (ATA) to Atezolizumab		Day 1 of all cycles (Cycle length = 21 days) and at treatment discontinuation (data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Szabados B, Ponz-Sarvise M, Machado R, Saldana D, Kadel EE, Banchereau R, Bouquet F, Garmhausen M, Powles T, Schroder C; imCORE Working Group of Early Career Investigators (imFLAME). Clinico-Genomic Characterization of Patients with Metastatic Urothelial Carcinoma in Real-World Practice Identifies a Novel Bladder Immune Performance Index (BIPI). Clin Cancer Res. 2022 Sep 15;28(18):4083-4091. doi: 10.1158/1078-0432.CCR-22-0200.
• Vander Velde N, Guerin A, Ionescu-Ittu R, Shi S, Wu EQ, Lin SW, Hsu LI, Saum KU, de Ducla S, Wang J, Li S, Thastrom A, Liu S, Shi L, Leppert JT. Comparative Effectiveness of Non-cisplatin First-line Therapies for Metastatic Urothelial Carcinoma: Phase 2 IMvigor210 Study Versus US Patients Treated in the Veterans Health Administration. Eur Urol Oncol. 2019 Feb;2(1):12-20. doi: 10.1016/j.euo.2018.07.003. Epub 2018 Aug 4.

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2014
• Primary Completion (Actual): July 4, 2016
• Study Completion (Actual): February 28, 2023

Study Registration Dates

• First Submitted: October 31, 2016
• First Submitted That Met QC Criteria: October 31, 2016
• First Posted (Estimated): November 1, 2016

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: bladder cancer; PD-1; PD-L1; atezolizumab; anti-PD-L1; MPDL3280A; Tecentriq
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Atezolizumab
• Other Study ID Numbers: GO29293 (Cohort 1); IMvigor 210 (Other Identifier: Genentech Inc.); 2013-005486-39 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No