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

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02951767
• Collaborator: (none)
• Enrollment: 119
• Locations: 77
• Arm: 1
• Anticipated Duration (Months): 105.9
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer	Drug: Atezolizumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 119 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Multicenter, Single-Arm Study of Atezolizumab in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
• Actual Study Start Date: May 31, 2014
• Actual Primary Completion Date: May 31, 2015
• Anticipated Study Completion Date: Mar 27, 2023

Arms and Interventions

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: MPDL3280A Tecentriq

Outcome Measures

Primary Outcome Measures

1. 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 [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)]

   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.

Secondary Outcome Measures

1. Duration of Response (DOR) as Assessed by the IRF According to RECIST v1.1 [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 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.

2. DOR as Assessed by the Investigator According to RECIST v1.1 [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 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.

3. Percentage of Participants With Death or Disease Progression as Assessed by the IRF According to RECIST v1.1 [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)]

   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.

4. Progression-Free Survival (PFS) as Assessed by the IRF According to RECIST v1.1 [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 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.

5. Percentage of Participants With Death or Disease Progression as Assessed by the Investigator According to RECIST v1.1 [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)]

   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.

6. PFS as Assessed by the Investigator According to RECIST v1.1 [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 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.

7. Percentage of Participants With a Confirmed Objective Response of CR or PR as Assessed by the Investigator According RECIST v1.1 [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)]

   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.

8. Percentage of Participants Who Died [Baseline until death (data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)]

   The percentage of participants who died from any cause was reported.

9. Overall Survival (OS) [Baseline until death (data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)]

   OS was defined as the time from start of treatment to the time of death from any cause on study.

10. Percentage of Participants Alive at 1-year [1-year]

11. 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)]

12. Minimum Serum Concentration (Cmin) of Atezolizumab [Pre-dose (0 hours) on Day 1 of Cycles 1, 2, 3, 4, 8 (Cycle length = 21 days)]

13. 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)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02951767
• Other Study ID Numbers: GO29293 (Cohort 1); IMvigor 210; 2013-005486-39
• First Posted: Nov 1, 2016
• Last Update Posted: Jun 28, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Hoffmann-La Roche: anti-PD-L1; PD-L1; MPDL3280A; PD-1; bladder cancer; atezolizumab; Tecentriq
• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Atezolizumab

Study Results

Participant Flow

Pre-assignment Detail	The analysis included data up to cutoff date 04 July 2016.

Arm/Group Title	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
Arm/Group Description	Participants with advanced disease who were treatment-naive for advanced urothelial carcinoma and cisplatin ineligible received atezolizumab 1200 milligrams (mg) via intravenous (IV) on Day 1 of 21-day cycles until disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria or unmanageable toxicity.
Period Title: Overall Study
STARTED	119
COMPLETED	0
NOT COMPLETED	119

Baseline Characteristics

Arm/Group Title	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
Arm/Group Description	Participants with advanced disease who were treatment-naive for advanced urothelial carcinoma and cisplatin ineligible received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.
Overall Participants	119
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.8 (8.9)
Sex: Female, Male (Count of Participants)
Female	23 19.3%
Male	96 80.7%

Outcome Measures

1. Primary Outcome

Title	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
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Cohort 1 objective response-evaluable population included intent-to-treat (ITT) participants who had measurable disease per RECIST v1.1 at baseline. Cohort 1 ITT population included all participants from Cohort 1 who received any amount of study drug.

Arm/Group Title	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
Arm/Group Description	Participants with advanced disease who were treatment-naive for advanced urothelial carcinoma and cisplatin ineligible received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.
Measure Participants	119
Number (95% Confidence Interval) [percentage of participants]	22.7 19.1%

2. Secondary Outcome

Title	Duration of Response (DOR) as Assessed by the IRF According to RECIST v1.1
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Cohort 1 objective response-evaluable population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
Arm/Group Description	Participants with advanced disease who were treatment-naive for advanced urothelial carcinoma and cisplatin ineligible received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.
Measure Participants	27
Median (Full Range) [months]	NA

3. Secondary Outcome

Title	DOR as Assessed by the Investigator According to RECIST v1.1
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Cohort 1 objective response-evaluable population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
Arm/Group Description	Participants with advanced disease who were treatment-naive for advanced urothelial carcinoma and cisplatin ineligible received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.
Measure Participants	30
Median (Full Range) [months]	NA

4. Secondary Outcome

Title	Percentage of Participants With Death or Disease Progression as Assessed by the IRF According to RECIST v1.1
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Cohort 1 ITT population.

Arm/Group Title	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
Arm/Group Description	Participants with advanced disease who were treatment-naive for advanced urothelial carcinoma and cisplatin ineligible received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.
Measure Participants	119
Number [percentage of participants]	73.9 62.1%

5. Secondary Outcome

Title	Progression-Free Survival (PFS) as Assessed by the IRF According to RECIST v1.1
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Cohort 1 ITT population.

Arm/Group Title	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
Arm/Group Description	Participants with advanced disease who were treatment-naive for advanced urothelial carcinoma and cisplatin ineligible received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.
Measure Participants	119
Median (95% Confidence Interval) [months]	2.69

6. Secondary Outcome

Title	Percentage of Participants With Death or Disease Progression as Assessed by the Investigator According to RECIST v1.1
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Cohort 1 ITT population.

Arm/Group Title	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
Arm/Group Description	Participants with advanced disease who were treatment-naive for advanced urothelial carcinoma and cisplatin ineligible received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.
Measure Participants	119
Number [percentage of participants]	71.4 60%

7. Secondary Outcome

Title	PFS as Assessed by the Investigator According to RECIST v1.1
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Cohort 1 ITT population.

Arm/Group Title	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
Arm/Group Description	Participants with advanced disease who were treatment-naive for advanced urothelial carcinoma and cisplatin ineligible received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.
Measure Participants	119
Median (95% Confidence Interval) [months]	4.17

8. Secondary Outcome

Title	Percentage of Participants With a Confirmed Objective Response of CR or PR as Assessed by the Investigator According RECIST v1.1
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Cohort 1 objective response-evaluable population.

Arm/Group Title	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
Arm/Group Description	Participants with advanced disease who were treatment-naive for advanced urothelial carcinoma and cisplatin ineligible received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.
Measure Participants	119
Number (95% Confidence Interval) [percentage of participants]	25.2 21.2%

9. Secondary Outcome

Title	Percentage of Participants Who Died
Description	The percentage of participants who died from any cause was reported.
Time Frame	Baseline until death (data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)

Outcome Measure Data

Analysis Population Description

Cohort 1 ITT population.

Arm/Group Title	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
Arm/Group Description	Participants with advanced disease who were treatment-naive for advanced urothelial carcinoma and cisplatin ineligible received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.
Measure Participants	119
Number [percentage of participants]	49.6 41.7%

10. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from start of treatment to the time of death from any cause on study.
Time Frame	Baseline until death (data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)

Outcome Measure Data

Analysis Population Description

Cohort 1 ITT population.

Arm/Group Title	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
Arm/Group Description	Participants with advanced disease who were treatment-naive for advanced urothelial carcinoma and cisplatin ineligible received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.
Measure Participants	119
Median (95% Confidence Interval) [months]	15.9

11. Secondary Outcome

Title	Percentage of Participants Alive at 1-year
Time Frame	1-year

Outcome Measure Data

Analysis Population Description

Cohort 1 ITT population.

Arm/Group Title	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
Arm/Group Description	Participants with advanced disease who were treatment-naive for advanced urothelial carcinoma and cisplatin ineligible received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.
Measure Participants	119
Number (95% Confidence Interval) [percentage of participants]	57.2 48.1%

12. Secondary Outcome

Title	Maximum Serum Concentration (Cmax) of Atezolizumab
Time Frame	Pre-dose (0 hours) and 30 minutes post-dose on Day 1 of Cycle 1 (Cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

Cohort 1 pharmacokinetic (PK) evaluable population was defined as participants who received any dose of atezolizumab treatment and had PK data at timepoints that were sufficient to determine PK parameters. Here, number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
Arm/Group Description	Participants with advanced disease who were treatment-naive for advanced urothelial carcinoma and cisplatin ineligible received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.
Measure Participants	113
Mean (Standard Deviation) [microgram(s)/milliliter (mcg/mL)]	386 (118)

13. Secondary Outcome

Title	Minimum Serum Concentration (Cmin) of Atezolizumab
Time Frame	Pre-dose (0 hours) on Day 1 of Cycles 1, 2, 3, 4, 8 (Cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

Cohort 1 PK evaluable population. Here, number of participants analyzed = participants who were evaluable for this outcome. "n" = participants who were evaluable at specified timepoint.

Arm/Group Title	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
Arm/Group Description	Participants with advanced disease who were treatment-naive for advanced urothelial carcinoma and cisplatin ineligible received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.
Measure Participants	117
Pre-dose Cycle 1 (n=117)	0 (0)
Pre-dose Cycle 2 (n=106)	77.7 (35.3)
Pre-dose Cycle 3 (n=57)	117 (48.8)
Pre-dose Cycle 4 (n=66)	159 (68.4)
Pre-dose Cycle 8 (n=47)	169 (110)

14. Secondary Outcome

Title	Percentage of Participants Positive for Anti-therapeutic Antibodies (ATA) to Atezolizumab
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Cohort 1 Safety Evaluable Population. Here, number of participants analyzed = participants for whom ATA samples were available.

Arm/Group Title	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
Arm/Group Description	Participants with advanced disease who were treatment-naive for advanced urothelial carcinoma and cisplatin ineligible received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.
Measure Participants	111
Number [percentage of participants]	47.7 (0) 40.1%

Adverse Events

Time Frame	First dose of study drug until data cutoff date 04 July 2016 (up to maximum length of follow-up of 23.52 months)
Adverse Event Reporting Description	Cohort 1 Safety Evaluable Population.
Arm/Group Title	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
Arm/Group Description	Participants with advanced disease who were treatment-naive for advanced urothelial carcinoma and cisplatin ineligible received atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.
All Cause Mortality
	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
	Affected / at Risk (%)	# Events
Total	45/119 (37.8%)
Blood and lymphatic system disorders
Leukocytosis	1/119 (0.8%)
Anaemia	2/119 (1.7%)
Cardiac disorders
Arrhythmia	1/119 (0.8%)
Cardiac arrest	1/119 (0.8%)
Cardiac failure	1/119 (0.8%)
Myocardial infarction	1/119 (0.8%)
Ear and labyrinth disorders
Vertigo	1/119 (0.8%)
Gastrointestinal disorders
Colitis	1/119 (0.8%)
Diarrhoea	3/119 (2.5%)
Ileus	1/119 (0.8%)
Nausea	1/119 (0.8%)
Small intestinal obstruction	3/119 (2.5%)
Vomiting	1/119 (0.8%)
Abdominal pain lower	1/119 (0.8%)
Autoimmune colitis	1/119 (0.8%)
General disorders
Asthenia	2/119 (1.7%)
Pyrexia	2/119 (1.7%)
Hepatobiliary disorders
Liver disorder	1/119 (0.8%)
Immune system disorders
Hypersensitivity	1/119 (0.8%)
Infections and infestations
Bacteraemia	1/119 (0.8%)
Biliary sepsis	1/119 (0.8%)
Influenza	1/119 (0.8%)
Meningoencephalitis herpetic	1/119 (0.8%)
Pneumonia	1/119 (0.8%)
Sepsis	3/119 (2.5%)
Urinary tract infection	1/119 (0.8%)
Urosepsis	1/119 (0.8%)
Bursitis infective	1/119 (0.8%)
Injury, poisoning and procedural complications
Joint injury	1/119 (0.8%)
Investigations
Blood bilirubin increased	1/119 (0.8%)
Blood creatine phosphokinase increased	1/119 (0.8%)
Blood creatinine increased	2/119 (1.7%)
Metabolism and nutrition disorders
Dehydration	2/119 (1.7%)
Hyponatraemia	1/119 (0.8%)
Failure to thrive	1/119 (0.8%)
Musculoskeletal and connective tissue disorders
Back pain	1/119 (0.8%)
Pathological fracture	1/119 (0.8%)
Rhabdomyolysis	1/119 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas	1/119 (0.8%)
Nervous system disorders
Aphasia	1/119 (0.8%)
Transient ischaemic attack	1/119 (0.8%)
Product Issues
Thrombosis in device	1/119 (0.8%)
Psychiatric disorders
Confusional state	1/119 (0.8%)
Mental status changes	1/119 (0.8%)
Renal and urinary disorders
Acute kidney injury	4/119 (3.4%)
Haematuria	1/119 (0.8%)
Renal failure	4/119 (3.4%)
Urinary retention	1/119 (0.8%)
Respiratory, thoracic and mediastinal disorders
Pulmonary artery thrombosis	1/119 (0.8%)
Pulmonary embolism	1/119 (0.8%)
Respiratory failure	1/119 (0.8%)
Vascular disorders
Deep vein thrombosis	1/119 (0.8%)
Haematoma	1/119 (0.8%)
Hypotension	1/119 (0.8%)
Other (Not Including Serious) Adverse Events
	Cohort 1: Treatment-naive Cisplatin Ineligible Participants
	Affected / at Risk (%)	# Events
Total	107/119 (89.9%)
Blood and lymphatic system disorders
Anaemia	21/119 (17.6%)
Endocrine disorders
Hypothyroidism	9/119 (7.6%)
Gastrointestinal disorders
Abdominal pain	8/119 (6.7%)
Constipation	18/119 (15.1%)
Diarrhoea	24/119 (20.2%)
Nausea	25/119 (21%)
Vomiting	18/119 (15.1%)
General disorders
Asthenia	9/119 (7.6%)
Chills	9/119 (7.6%)
Fatigue	54/119 (45.4%)
Oedema peripheral	19/119 (16%)
Pain	6/119 (5%)
Pyrexia	16/119 (13.4%)
Infections and infestations
Upper respiratory tract infection	8/119 (6.7%)
Urinary tract infection	18/119 (15.1%)
Investigations
Alanine aminotransferase increased	9/119 (7.6%)
Aspartate aminotransferase increased	8/119 (6.7%)
Blood alkaline phosphatase increased	6/119 (5%)
Blood creatinine increased	18/119 (15.1%)
Weight decreased	8/119 (6.7%)
Metabolism and nutrition disorders
Decreased appetite	28/119 (23.5%)
Hyperglycaemia	8/119 (6.7%)
Hyperkalaemia	6/119 (5%)
Hyponatraemia	8/119 (6.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	19/119 (16%)
Back pain	16/119 (13.4%)
Pain in extremity	8/119 (6.7%)
Musculoskeletal pain	6/119 (5%)
Nervous system disorders
Dizziness	10/119 (8.4%)
Headache	10/119 (8.4%)
Psychiatric disorders
Anxiety	9/119 (7.6%)
Depression	6/119 (5%)
Insomnia	8/119 (6.7%)
Renal and urinary disorders
Haematuria	10/119 (8.4%)
Respiratory, thoracic and mediastinal disorders
Cough	15/119 (12.6%)
Dyspnoea	11/119 (9.2%)
Skin and subcutaneous tissue disorders
Dry skin	8/119 (6.7%)
Pruritus	21/119 (17.6%)
Rash	12/119 (10.1%)
Vascular disorders
Hypotension	7/119 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.