IMvigor010: A Study of Atezolizumab Versus Observation as Adjuvant Therapy in Participants With High-Risk Muscle-Invasive Urothelial Carcinoma (UC) After Surgical Resection

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02450331
• Collaborator: (none)
• Enrollment: 809
• Locations: 186
• Arms: 2
• Actual Duration (Months): 79.8
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This Phase III, open-label, randomized, multicenter study is to evaluate the efficacy and safety of adjuvant treatment with atezolizumab compared with observation in participants with muscle-invasive UC who are at high risk for recurrence following resection. Eligible participants were randomized by a 1:1 ratio into atezolizumab group or control group.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Transitional Cell	Drug: Atezolizumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 809 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Open-Label, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Versus Observation as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Urothelial Carcinoma After Surgical Resection
• Actual Study Start Date: Oct 5, 2015
• Actual Primary Completion Date: Nov 30, 2019
• Actual Study Completion Date: May 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Atezolizumab Participants will receive intravenous (IV) atezolizumab on Day 1 of each 21-day cycle for 16 cycles (up to 1 year).	Drug: Atezolizumab; Atezolizumab will be administered at a dose of 1200 milligrams (mg).; Other Names: TECENTRIQ®; MPDL3280A
No Intervention: Observation Participants will undergo observation starting on Day 1 for 16 cycles (up to 1 year).

Outcome Measures

Primary Outcome Measures

1. Disease-Free Survival (DFS), as Assessed by Investigator [Randomization up to first occurrence of DFS event (up to approximately 50 months)]

   DFS is defined as the time from randomization to the time of first occurrence of a DFS event. DFS events include: local (pelvic) recurrence of UC (including soft tissue and regional lymph nodes); urinary tract recurrence of UC (including all pathological stages and grades); distant metastasis of UC; or death from any cause. Tumor assessment will be performed using radiographic evaluations.

Secondary Outcome Measures

1. Overall Survival (OS) [Randomization until death due to any cause (up to approximately 50 months)]

   Overall survival is defined as the time from randomization to the date of death from any cause, regardless of whether the death occurs during study treatment or following treatment discontinuation.

2. Disease-Specific Survival (DSS), as Assessed by Investigator [Randomization until death due to UC (up to approximately 50 months)]

   DSS is defined as the time from randomization until the date of death from UC.

3. Distant Metastasis-Free Survival (DMFS) [Randomization up to diagnosis of distant metastases or death from any cause (up to approximately 50 months)]

   DMFS is defined as the time from randomization to the date of diagnosis of distant (that is, non-locoregional) metastases or death from any cause. Tumor assessment will be performed using radiographic evaluations.

4. Non-Urinary Tract Recurrence-Free Survival (NURFS) [Randomization up to time of first occurrence of a NURFS event (up to approximately 50 months)]

   NURFS is defined as the time from randomization to the time of first occurrence of a NURFS event. NURFS events include: local (pelvic) recurrence of UC (including soft tissue and regional lymph nodes); distant metastasis of UC; or death from any cause. Tumor assessment will be performed using radiographic evaluations.

5. Percentage of Participants With Adverse Events (AEs) [Screening up to approximately 50 months]

   Percentage of participants with at least one Adverse Event.

6. Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab [Baseline up to approximately 50 months]

   Percentage of participants with anti-therapeutic antibodies to atezolizumab.

7. EuroQol 5-Dimension 5-Level (EQ-5D-5L) Visual Analogue Scale Score [Day 1 of Cycle 1 up to approximately 50 months (Cycle length = 21 days)]

   The EQ-5D-5L is a generic preference-based HRQoL questionnaire that provides a single index value for health status and is used to inform pharmacoeconomic evaluations and to measure general health status. Visual analog scale (VAS) allows the patient to indicate, on a scale of 0-100, how his or her health is on the day of assessment, with 100 being the "best imaginable health state" and 0 being the "worst imaginable health state."

8. Minimum Observed Serum Atezolizumab Concentration (Cmin) [Pre-dose (Hour 0) on Day 1 of Cycles 1, 2, 3, 4, every 8 cycles from Cycle 8, at treatment discontinuation, 120 days after treatment discontinuation (up to approximately 50 months))(Cycle length = 21 days)]

   Minimum observed serum atezolizumab concentration (Cmin) prior to infusion on Day 1 of Cycles 1, 2, 3, and 4; every 8 cycles starting on Cycle 8; at treatment discontinuation; and at 120 days after the last dose of atezolizumab.

9. Maximum Observed Serum Atezolizumab Concentration (Cmax) [Day 1 of Cycle 1 (Cycle length = 21 days)]

   Maximum observed serum atezolizumab concentration (Cmax) after infusion on Day 1 of Cycle 1.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed muscle-invasive UC (also termed transitional cell carcinoma) of the bladder or upper urinary tract (i.e., renal pelvis or ureters)

• For participants treated with prior neoadjuvant chemotherapy: tumor stage of ypT2-4a or ypN+ (ypT2-4 or ypN+ for participants with upper urinary tract UC) and M0

• For participants who have not received prior neoadjuvant chemotherapy: tumor stage of pT3-4a or pN+ (pT3-4 or pN+ for participants with upper urinary tract UC) and M0

• Representative formalin-fixed paraffin-embedded tumor specimens from surgical resection (i.e., radical cystectomy, nephroureterectomy, or lymph node dissection) in paraffin blocks (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for central testing and determined to be evaluable for tumor programmed death-ligand 1 (PD-L1) expression prior to study enrollment

• Absence of residual disease and absence of metastasis, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging scan of the pelvis, abdomen, and chest no more than 4 weeks prior to randomization

• Full recovery from cystectomy or nephroureterectomy within 14 weeks following surgery

• Eastern Cooperative Oncology Group performance status of less than or equal to (</=) 2

• Life expectancy greater than or equal to (>/=) 12 weeks

• Adequate hematologic and end-organ function

• For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or use contraceptive methods that result in a failure rate of less than (<) 1 percent (%) per year during the treatment period and for at least 5 months after the last dose of atezolizumab

Exclusion Criteria:

• Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment

• Adjuvant chemotherapy or radiation therapy for UC following surgical resection

• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or five half-lives of the drug prior to enrollment

• Malignancies other than UC within 5 years prior to Cycle 1, Day 1

• Pregnancy or breastfeeding

• Significant cardiovascular disease

• Severe infections within 4 weeks prior to Cycle 1, Day 1

• Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1

• 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

• Prior allogeneic stem cell or solid organ transplant

• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan

• Positive test for human immunodeficiency virus and/or active hepatitis B or hepatitis C or tuberculosis

• Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1

• Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-CD40, anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HonorHealth Research Institute - Pima - Virginia G. Piper Cancer Care Network	Scottsdale	Arizona	United States	85258
2	UCLA	Los Angeles	California	United States	90024
3	USC Norris Cancer Center	Los Angeles	California	United States	90033
4	Stanford University Medical Center	Palo Alto	California	United States	94304
5	University Of Colorado	Aurora	Colorado	United States	80045
6	The Urology Center of Colorado	Denver	Colorado	United States	80211
7	Yale Cancer Center; Medical Oncology	New Haven	Connecticut	United States	06520
8	Northwestern University Feinberg School Of Medicine	Chicago	Illinois	United States	60611
9	University of Chicago; Hematology/Oncology	Chicago	Illinois	United States	60637
10	University of Iowa Hospital & Clinic; Division of Hematology/Oncology	Iowa City	Iowa	United States	52242
11	Albert B. Chandler Medical Center; University of Kentucky	Lexington	Kentucky	United States	40536
12	Norton Cancer Institute	Louisville	Kentucky	United States	40202
13	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland	United States	21287
14	Chesapeake Urology Research Associates	Towson	Maryland	United States	21204
15	Massachusetts General Hospital.	Boston	Massachusetts	United States	02114
16	Dana Farber Cancer Inst.	Boston	Massachusetts	United States	02115
17	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
18	University Of Michigan	Ann Arbor	Michigan	United States	48109
19	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
20	Henry Ford Health System	Detroit	Michigan	United States	48202
21	MSK @Basking Ridge	Basking Ridge	New Jersey	United States	07920
22	Saint Barnabas Medical Center Cancer Center	Livingston	New Jersey	United States	07039
23	Memorial Sloan-Kettering Cancer Center	Commack	New York	United States	11725
24	Laura and ISAAC Perlmutter Cancer Center at NYU Langone.	New York	New York	United States	10016
25	Columbia University Medical Center	New York	New York	United States	10032
26	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
27	Duke Cancer Center	Durham	North Carolina	United States	27710
28	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
29	Cleveland Clinic	Cleveland	Ohio	United States	44106
30	Fairview Hospital; Cleveland Clinic Cancer Center	Cleveland	Ohio	United States	44111
31	The Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43212
32	Cleveland CL N Coast Cancer Cr	Sandusky	Ohio	United States	44870
33	Abramson Cancer Center; Univ of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
34	Kimmel Cancer Center Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
35	Fox Chase-Temple Cancer Center	Philadelphia	Pennsylvania	United States	19111
36	Miriam Hospital	Providence	Rhode Island	United States	02906
37	University of Texas Southwestern	Dallas	Texas	United States	75390-8897
38	Baylor College of Medicine; Gastroenterology	Houston	Texas	United States	77030
39	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
40	University of Virginia	Charlottesville	Virginia	United States	22906
41	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
42	Macquarie University Hospital	Macquarie Park	New South Wales	Australia	2109
43	Royal Brisbane & Women's Hosp; Cancer Care Serv	Herston	Queensland	Australia	4029
44	Monash Medical Centre; Oncology	Clayton	Victoria	Australia	3168
45	Austin and Repatriation Medical Centre; Cancer Services	Melbourne	Victoria	Australia	3084
46	Institut Jules Bordet	Anderlecht		Belgium	1070
47	Cliniques Universitaires St-Luc	Bruxelles		Belgium	1200
48	UZ Gent	Gent		Belgium	9000
49	UZ Leuven Gasthuisberg	Leuven		Belgium	3000
50	Cross Cancer Institute ; Dept of Medical Oncology	Edmonton	Alberta	Canada	T6G 1Z2
51	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
52	Royal Victoria Hospital	Barrie	Ontario	Canada	L4M 6M2
53	London Regional Cancer Centre	London	Ontario	Canada	N6A 4L6
54	Lakeridge Health Oshawa; Oncology	Oshawa	Ontario	Canada	L1G 2B9
55	The Ottawa Hospital Cancer Centre; Oncology	Ottawa	Ontario	Canada	K1H 8L6
56	North York General Hospital	Toronto	Ontario	Canada	M2J 1V1
57	Sunnybrook Odette Cancer Centre	Toronto	Ontario	Canada	M4N 3M5
58	McGill University; Glen Site; Oncology	Montreal	Quebec	Canada	H4A 3J1
59	CHU de Quebec Hotel-Dieu de Quebec	Quebec City	Quebec	Canada	G1R 2J6
60	Peking University First Hospital	Beijing City		China	100034
61	Friendship Hospital, Capital Medical University	Beijing		China	100050
62	Beijing Cancer Hospital	Beijing		China	100142
63	The Second Affiliated Hospital, Sun Yat-sen University	Guangzhou City		China	510120
64	Jiangsu Cancer Hospital	Nanjing City		China	211100
65	Jiangsu Province Hospital	Nanjing		China	210036
66	Huashan Hospital Affiliated to Fudan University	Shanghai City		China	200040
67	Fudan University Shanghai Cancer Center	Shanghai City		China	200120
68	Zhongshan Hospital Fudan University	Shanghai		China	200032
69	Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai		China	200092
70	Masarykuv onkologicky ustav	Brno		Czechia	656 53
71	Fakultni nemocnice Olomouc; Onkologicka klinika	Olomouc		Czechia	779 00
72	Multiscan s.r.o.	Pardubice		Czechia	532 03
73	University Hospital Motol; Department of Urology	Praha 5		Czechia	15006
74	Helsinki University Central Hospital; Urology Clinics	Helsinki		Finland	00029
75	Tampere University Hospital; Dept Of Urology	Tampere		Finland	33520
76	Turku University Central Hospital; Urology clinic	Turku		Finland	20520
77	ICO Paul Papin; Oncologie Medicale.	Angers		France	49055
78	Institut Sainte Catherine;Recherche Clinique	Avignon		France	84918
79	Hopital Saint Andre	Bordeaux		France	33075
80	Centre Francois Baclesse; Recherche Clinique	Caen		France	14076
81	Centre Jean Perrin	Clermont Ferrand		France	63011
82	Centre Leon Berard; Departement Oncologie Medicale	Lyon		France	69373
83	Centre D'Oncologie de Gentilly; Oncology	Nancy		France	54100
84	Centre Antoine Lacassagne	Nice		France	06189
85	Hopital Cochin; Unite Fonctionnelle D Oncologie	Paris		France	75014
86	Hopital Saint Louis; Oncologie Medicale	Paris		France	75475
87	Institut Mutualiste Montsouris; Oncologie	Paris		France	75674
88	Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale	Paris		France	75908
89	ICO - Site René Gauducheau	Saint Herblain		France	44805
90	Institut Claudius Regaud; Departement Oncologie Medicale	Toulouse		France	31059
91	Campus Charitè Mitte Charité Centrum 10. Klinik f.Urologie	Berlin		Germany	10117
92	Augusta-Kranken-Anstalt gGmbH; Klinik für Hämatologie, Onkologie & Palliativmedizin	Bochum		Germany	44791
93	Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Urologie	Dresden		Germany	01307
94	Universitätsklinikum Düsseldorf; Urologische Klinik	Düsseldorf		Germany	40225
95	Universitätsklinikum der Ruhr-Universität Bochum, Marien-Hospital Herne, Urologische Klinik	Herne		Germany	44625
96	Medizinische Fakultät Mannheim, Universitätsklinikum Mannheim, Klinik für Urologie	Mannheim		Germany	68167
97	Klinikum rechts der Isar der TU München; Urologische Klinik und Poliklinik	München		Germany	81675
98	Universitätsmedizin Rostock, Urologische Klinik und Poliklinik	Rostock		Germany	18057
99	Diakonie-Klinikum Stuttgart; Urologische Klinik	Stuttgart		Germany	70176
100	Universitätsklinikum Tübingen; Klinik für Urologie	Tübingen		Germany	72076
101	Universitätsklinikum Ulm; Klinik für Urologie	Ulm		Germany	89081
102	Alexandras General Hospital of Athens; Oncology Department	Athens		Greece	115 28
103	University Hospital of Patras Medical Oncology	Patras		Greece	265 04
104	Rambam Health Care Campus; Oncology - Hafia	Hafia		Israel	3109601
105	Hadassah Ein Karem Hospital; Oncology Dept	Jerusalem		Israel	9112000
106	Meir Medical Center; Oncology	Kfar-Saba		Israel	4428164
107	Rabin Medical Center; Oncology Dept	Petach Tikva		Israel	4941492
108	Chaim Sheba Medical Center; Oncology Dept	Ramat Gan		Israel	5262100
109	Tel-Aviv Sourasky Medical Center	Tel Aviv		Israel	6423906
110	Assaf Harofeh; Oncology	Zerifin		Israel	6093000
111	Az. Osp. Cardarelli; Divisione Di Oncologia	Napoli	Campania	Italy	80131
112	ISTITUTO NAZIONALE TUMORI IRCCS FONDAZIONE G. PASCALE; Dipartimento Uro-Ginecologico	Napoli	Campania	Italy	80131
113	Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica	Bologna	Emilia-Romagna	Italy	40138
114	IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica	Meldola	Emilia-Romagna	Italy	47014
115	Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica	Roma	Lazio	Italy	00152
116	Irccs Ospedale San Raffaele;Oncologia Medica	Milano	Lombardia	Italy	20132
117	Irccs Istituto Europeo Di Oncologia (IEO); Cure Mediche	Milano	Lombardia	Italy	20141
118	A.O. UNIVERSITARIA S. LUIGI GONZAGA; Oncologia Medica	Orbassano	Piemonte	Italy	10043
119	Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia	Arezzo	Toscana	Italy	52100
120	Azienda Ospedaliera S. Maria - Terni; Oncologia	Terni	Umbria	Italy	05100
121	Nagoya University Hospital; Urology	Aichi		Japan	466-8560
122	Hirosaki University School of Medicine & Hospital; Urology	Aomori		Japan	036-8563
123	Shikoku Cancer Center	Ehime		Japan	791-0280
124	Hiroshima City Hiroshima Citizens Hospital; Urology	Hiroshima		Japan	730-8518
125	National Hospital Organization Hokkaido Cancer Center	Hokkaido		Japan	003-0804
126	University of Tsukuba Hospital	Ibaraki		Japan	305-8576
127	Iwate Medical University Hospital; Urology	Iwate		Japan	028-3695
128	Kyoto University Hospital	Kyoto		Japan	606-8507
129	Okayama University Hospital	Okayama		Japan	700-8558
130	Osaka University Hospital; Urology	Osaka		Japan	565-0871
131	Kindai University Hospital; Urology	Osaka		Japan	589-8511
132	Saitama Medical University International Medical Center	Saitama		Japan	350-1298
133	Shizuoka Cancer Center; Urology	Shizuoka		Japan	411-8777
134	National Cancer Center Hospital; Urology	Tokyo		Japan	104-0045
135	The University of Tokyo Hospital	Tokyo		Japan	113-8655
136	The Cancer Institute Hospital, JFCR; Urology	Tokyo		Japan	135-8550
137	Kyorin University Hospital	Tokyo		Japan	181-8611
138	National Cancer Center	Goyang-si		Korea, Republic of	10408
139	Asan Medical Center	Seoul		Korea, Republic of	05505
140	Samsung Medical Center	Seoul		Korea, Republic of	06351
141	NKI/AvL	Amsterdam		Netherlands	1066 CX
142	VU MEDISCH CENTRUM; Dept. of Medical Oncology	Amsterdam		Netherlands	1081 HV
143	Academ Ziekenhuis Groningen; Medical Oncology	Groningen		Netherlands	9713 GZ
144	Erasmus Mc - Daniel Den Hoed Kliniek; Interne Oncologie	Rotterdam		Netherlands	3015AA
145	St. Antonius locatie Leidsche Rijn	Utrecht		Netherlands	3543 AZ
146	KO-MED Centra Kliniczne Lublin II	Lublin		Poland	20-362
147	Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu; Oddział Chemioterapii	Poznań		Poland	60-569
148	SpecjalistycznySzpital Miejski w Toruniu; Oddział Urologii Ogólnej i Onkologicznej	Toruń		Poland	87-100
149	Szpital Kliniczny Dzieciątka Jezus; Oddział Urologii	Warszawa		Poland	02-005
150	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego; Oddzial Urologii i Onkologii	Wroclaw		Poland	50-556
151	Sverdlovsk Regional Oncology Dispensary; Chemotherapy	Ekaterinburg		Russian Federation	620905
152	Ivanovo Regional Oncology Dispensary	Ivanovo		Russian Federation	153040
153	P.A. Herzen Oncological Inst. ; Oncology	Moscow		Russian Federation	125284
154	Privolzhsk Regional Medical Center	Nizhny Novgorod		Russian Federation	603001
155	SBEI of HPE "Bashkir State Medical University" of MoH RF	Ufa		Russian Federation	450000
156	Clinic for Urology; Clinical Hospital Center "Dragisa Misovic-Dedinje"	Belgrade		Serbia	11000
157	Clinical Center of Serbia; Clinic of Urology	Belgrade		Serbia	11000
158	Corporacio Sanitaria Parc Tauli; Servicio de Oncologia	Sabadell	Barcelona	Spain	8208
159	Hospital de Donostia; Servicio de Oncologia Medica	San Sebastian	Guipuzcoa	Spain	20080
160	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona		Spain	08035
161	Hospital Clinic de Barcelona. Unidad de Nuevas Terapias;Oncology Department	Barcelona		Spain	08036
162	Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia	Barcelona		Spain	08041
163	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid		Spain	28007
164	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid		Spain	28034
165	Hospital Clinico San Carlos; Servicio de Oncologia	Madrid		Spain	28040
166	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid		Spain	28041
167	Hospital Universitario La Paz; Servicio de Oncologia	Madrid		Spain	28046
168	Instituto Valenciano Oncologia; Oncologia Medica	Valencia		Spain	46009
169	UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie	Zürich		Switzerland	8091
170	Taichung Veterans General Hospital; Division of Urology	Taichung		Taiwan	407
171	National Taiwan University Hospital, Department of Urology	Taipei		Taiwan	10048
172	Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology	Adana		Turkey	01230
173	Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department	Edirne		Turkey	22770
174	Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology	Istanbul		Turkey	34300
175	Medikal Park Izmir Hospital	Karşıyaka		Turkey	35575
176	Regional Clinical Center of Urology and Nephrology n.a. V.I. Shapoval Department of Urology #4	Kharkiv	Kharkiv Governorate	Ukraine	61037
177	CI Dnipropetrovsk CMCH #4 MA of MOHU Ch of Oncology and MR	Dnipropetrovsk		Ukraine	49102
178	GU "Institution of urology of Academy Medical science of Ukraine"	Kiev		Ukraine	04053
179	University Hospitals Birmingham NHS Foundation Trust	Birmingham		United Kingdom	B15 2TH
180	University Hospitals Bristol NHS Foundation Trust	Bristol		United Kingdom	BS2 8HW
181	Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 0YN
182	Barts Health NHS Trust - St Bartholomew's Hospital	London		United Kingdom	EC1A 7BE
183	Sarah Cannon Research Institute	London		United Kingdom	W1G 6AD
184	James Cook Uni Hospital	Middlesborough		United Kingdom	TS4 3BW
185	Royal Preston Hosptial	Preston		United Kingdom	PR2 9HT
186	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Apr 13, 2020
• Statistical Analysis Plan - Feb 1, 2019

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02450331
• Other Study ID Numbers: WO29636; 2014-005603-25
• First Posted: May 21, 2015
• Last Update Posted: Jul 8, 2022
• Last Verified: Jun 1, 2022

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Transitional Cell; Atezolizumab

Study Results

Participant Flow

Arm/Group Title	Observation	Atezolizumab
Arm/Group Description	Participants underwent observation starting on Day 1 for 16 cycles (up to 1 year).	Participants received intravenous (IV) atezolizumab on Day 1 of each 21-day cycle for 16 cycles (up to 1 year).
Period Title: Overall Study
STARTED	403	406
COMPLETED	0	0
NOT COMPLETED	403	406

Baseline Characteristics

Arm/Group Title	Observation	Atezolizumab	Total
Arm/Group Description	Participants underwent observation starting on Day 1 for 16 cycles (up to 1 year).	Participants received intravenous (IV) atezolizumab on Day 1 of each 21-day cycle for 16 cycles (up to 1 year).	Total of all reporting groups
Overall Participants	403	406	809
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	65.9 (9.3)	66.0 (9.0)	65.9 (9.1)
Sex: Female, Male (Count of Participants)
Female	87 21.6%	84 20.7%	171 21.1%
Male	316 78.4%	322 79.3%	638 78.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 2.2%	16 3.9%	25 3.1%
Not Hispanic or Latino	357 88.6%	369 90.9%	726 89.7%
Unknown or Not Reported	37 9.2%	21 5.2%	58 7.2%
Race/Ethnicity, Customized (Number of Participants) [Number]
American Indian or Alaska Native	0 0%	1 0.2%	1 0.1%
Asian	68 16.9%	64 15.8%	132 16.3%
Black or African American	3 0.7%	3 0.7%	6 0.7%
White	307 76.2%	320 78.8%	627 77.5%
Other	4 1%	6 1.5%	10 1.2%
Unknown	21 5.2%	12 3%	33 4.1%

Outcome Measures

1. Primary Outcome

Title	Disease-Free Survival (DFS), as Assessed by Investigator
Description	DFS is defined as the time from randomization to the time of first occurrence of a DFS event. DFS events include: local (pelvic) recurrence of UC (including soft tissue and regional lymph nodes); urinary tract recurrence of UC (including all pathological stages and grades); distant metastasis of UC; or death from any cause. Tumor assessment will be performed using radiographic evaluations.
Time Frame	Randomization up to first occurrence of DFS event (up to approximately 50 months)

Outcome Measure Data

Analysis Population Description

The ITT population is defined as all randomized patients, whether or not the patient received the assigned treatment (atezolizumab/observation).

Arm/Group Title	Observation	Atezolizumab
Arm/Group Description	Participants underwent observation starting on Day 1 for 16 cycles (up to 1 year).	Participants received intravenous (IV) atezolizumab on Day 1 of each 21-day cycle for 16 cycles (up to 1 year).
Measure Participants	403	406
Median (95% Confidence Interval) [Months]	16.6	19.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Observation, Atezolizumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2446
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.892
	Confidence Interval	(2-Sided) 95%; 0.735 to 1.081
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival is defined as the time from randomization to the date of death from any cause, regardless of whether the death occurs during study treatment or following treatment discontinuation.
Time Frame	Randomization until death due to any cause (up to approximately 50 months)

Outcome Measure Data

Analysis Population Description

The ITT population is defined as all randomized patients, whether or not the patient received the assigned treatment (atezolizumab/observation).

Arm/Group Title	Observation	Atezolizumab
Arm/Group Description	Participants underwent observation starting on Day 1 for 16 cycles (up to 1 year).	Participants received intravenous (IV) atezolizumab on Day 1 of each 21-day cycle for 16 cycles (up to 1 year).
Measure Participants	403	406
Median (95% Confidence Interval) [Months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Observation, Atezolizumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1951
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.846
	Confidence Interval	(2-Sided) 95%; 0.657 to 1.090
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Disease-Specific Survival (DSS), as Assessed by Investigator
Description	DSS is defined as the time from randomization until the date of death from UC.
Time Frame	Randomization until death due to UC (up to approximately 50 months)

Outcome Measure Data

Analysis Population Description

The ITT population is defined as all randomized patients, whether or not the patient received the assigned treatment (atezolizumab/observation).

Arm/Group Title	Observation	Atezolizumab
Arm/Group Description	Participants underwent observation starting on Day 1 for 16 cycles (up to 1 year).	Participants received intravenous (IV) atezolizumab on Day 1 of each 21-day cycle for 16 cycles (up to 1 year).
Measure Participants	403	406
Median (95% Confidence Interval) [Months]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Observation, Atezolizumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis
Statistical Test of Hypothesis	p-Value	0.2235
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.836
	Confidence Interval	(2-Sided) 95%; 0.626 to 1.116
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Distant Metastasis-Free Survival (DMFS)
Description	DMFS is defined as the time from randomization to the date of diagnosis of distant (that is, non-locoregional) metastases or death from any cause. Tumor assessment will be performed using radiographic evaluations.
Time Frame	Randomization up to diagnosis of distant metastases or death from any cause (up to approximately 50 months)

Outcome Measure Data

Analysis Population Description

The ITT population is defined as all randomized patients, whether or not the patient received the assigned treatment (atezolizumab/observation).

Arm/Group Title	Observation	Atezolizumab
Arm/Group Description	Participants underwent observation starting on Day 1 for 16 cycles (up to 1 year).	Participants received intravenous (IV) atezolizumab on Day 1 of each 21-day cycle for 16 cycles (up to 1 year).
Measure Participants	403	406
Median (95% Confidence Interval) [Months]	31.1	27.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Observation, Atezolizumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis
Statistical Test of Hypothesis	p-Value	0.4291
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.918
	Confidence Interval	(2-Sided) 95%; 0.743 to 1.134
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Non-Urinary Tract Recurrence-Free Survival (NURFS)
Description	NURFS is defined as the time from randomization to the time of first occurrence of a NURFS event. NURFS events include: local (pelvic) recurrence of UC (including soft tissue and regional lymph nodes); distant metastasis of UC; or death from any cause. Tumor assessment will be performed using radiographic evaluations.
Time Frame	Randomization up to time of first occurrence of a NURFS event (up to approximately 50 months)

Outcome Measure Data

Analysis Population Description

The ITT population is defined as all randomized patients, whether or not the patient received the assigned treatment (atezolizumab/observation).

Arm/Group Title	Observation	Atezolizumab
Arm/Group Description	Participants underwent observation starting on Day 1 for 16 cycles (up to 1 year).	Participants received intravenous (IV) atezolizumab on Day 1 of each 21-day cycle for 16 cycles (up to 1 year).
Measure Participants	403	406
Median (95% Confidence Interval) [Months]	19.5	22.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Observation, Atezolizumab
	Comments
	Type of Statistical Test	Superiority
	Comments	Stratified Analysis
Statistical Test of Hypothesis	p-Value	0.1994
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.879
	Confidence Interval	(2-Sided) 95%; 0.722 to 1.070
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs)
Description	Percentage of participants with at least one Adverse Event.
Time Frame	Screening up to approximately 50 months

Outcome Measure Data

Analysis Population Description

The safety population is defined as patients who received at least one dose of atezolizumab, and all patients who did not receive any dose of atezolizumab who had at least one post-baseline safety assessment (e.g.,adverse event, lab, vital signs, ECG, etc.), regardless of their assigned treatment (atezolizumab/observation).

Arm/Group Title	Observation	Atezolizumab
Arm/Group Description	Participants underwent observation starting on Day 1 for 16 cycles (up to 1 year).	Participants received intravenous (IV) atezolizumab on Day 1 of each 21-day cycle for 16 cycles (up to 1 year).
Measure Participants	397	390
Number [Percentage of Participants]	78.8 19.6%	94.4 23.3%

7. Secondary Outcome

Title	Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
Description	Percentage of participants with anti-therapeutic antibodies to atezolizumab.
Time Frame	Baseline up to approximately 50 months

Outcome Measure Data

Analysis Population Description

The anti-drug antibodies (ADA)-evaluable population is defined as all patients treated with atezolizumab who have at least one post-baseline ADA result.

Arm/Group Title	Atezolizumab
Arm/Group Description	Participants received intravenous (IV) atezolizumab on Day 1 of each 21-day cycle for 16 cycles (up to 1 year).
Measure Participants	375
Number [Percentage of Participants]	29.3 7.3%

8. Secondary Outcome

Title	EuroQol 5-Dimension 5-Level (EQ-5D-5L) Visual Analogue Scale Score
Description	The EQ-5D-5L is a generic preference-based HRQoL questionnaire that provides a single index value for health status and is used to inform pharmacoeconomic evaluations and to measure general health status. Visual analog scale (VAS) allows the patient to indicate, on a scale of 0-100, how his or her health is on the day of assessment, with 100 being the "best imaginable health state" and 0 being the "worst imaginable health state."
Time Frame	Day 1 of Cycle 1 up to approximately 50 months (Cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

The ITT population is defined as all randomized patients, whether or not the patient received the assigned treatment (atezolizumab/observation).

Arm/Group Title	Observation	Atezolizumab
Arm/Group Description	Participants underwent observation starting on Day 1 for 16 cycles (up to 1 year).	Participants received intravenous (IV) atezolizumab on Day 1 of each 21-day cycle for 16 cycles (up to 1 year).
Measure Participants	403	406
Cycle 1 Day 1	77.41 (15.74)	78.89 (16.13)
Cycle 3 Day 1	78.64 (15.73)	81.05 (14.96)
Cycle 5 Day 1	79.94 (16.32)	81.95 (14.32)
Cycle 7 Day 1	80.81 (16.37)	82.39 (14.43)
Cycle 9 Day 1	81.24 (15.70)	82.06 (15.34)
Cycle 11 Day 1	81.39 (17.02)	82.81 (14.96)
Cycle 13 Day 1	81.39 (16.99)	82.59 (14.81)
Cycle 15 Day 1	82.78 (16.01)	83.67 (14.47)
Treatment Discontinuation	82.68 (16.19)	81.91 (15.96)

9. Secondary Outcome

Title	Minimum Observed Serum Atezolizumab Concentration (Cmin)
Description	Minimum observed serum atezolizumab concentration (Cmin) prior to infusion on Day 1 of Cycles 1, 2, 3, and 4; every 8 cycles starting on Cycle 8; at treatment discontinuation; and at 120 days after the last dose of atezolizumab.
Time Frame	Pre-dose (Hour 0) on Day 1 of Cycles 1, 2, 3, 4, every 8 cycles from Cycle 8, at treatment discontinuation, 120 days after treatment discontinuation (up to approximately 50 months))(Cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

The pharmacokinetic-evaluable population is defined as all patients who received any dose of atezolizumab and who have evaluable pharmacokinetic (PK) samples.

Arm/Group Title	Atezolizumab
Arm/Group Description	Participants received intravenous (IV) atezolizumab on Day 1 of each 21-day cycle for 16 cycles (up to 1 year).
Measure Participants	380
Cycle 2 Day 1	78.4 (25.2)
Cycle 3 Day 1	125 (46.0)
Cycle 4 Day 1	152 (71.1)
Cycle 8 Day 1	203 (92.0)
Cycle 16 Day 1	225 (106)
Day 120 Post Last Dose MPDL3280A	15.9 (19.5)
Study Drug or Study Phase Comp or Early Disc	164 (106)

10. Secondary Outcome

Title	Maximum Observed Serum Atezolizumab Concentration (Cmax)
Description	Maximum observed serum atezolizumab concentration (Cmax) after infusion on Day 1 of Cycle 1.
Time Frame	Day 1 of Cycle 1 (Cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

The pharmacokinetic-evaluable population is defined as all patients who received any dose of atezolizumab and who have evaluable pharmacokinetic (PK) samples.

Arm/Group Title	Atezolizumab
Arm/Group Description	Participants received intravenous (IV) atezolizumab on Day 1 of each 21-day cycle for 16 cycles (up to 1 year).
Measure Participants	300
Mean (Standard Deviation) [µg/mL]	365 (121)

Adverse Events

Time Frame	From the first study drug to the data cutoff date: 30 Nov 2019 (up to 50 months)
Adverse Event Reporting Description	The safety-evaluable population for atezolizumab was defined as patients who received at least one dose of atezolizumab. The safety-evaluable population for observation was defined as patients randomized to observation who had at least one post-baseline safety assessment.
Arm/Group Title	OBSERVATION		ATEZOLIZUMAB
Arm/Group Description	Participants underwent observation starting on Day 1 for 16 cycles (up to 1 year).		Participants received intravenous (IV) atezolizumab on Day 1 of each 21-day cycle for 16 cycles (up to 1 year).
All Cause Mortality
	OBSERVATION		ATEZOLIZUMAB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	124/397 (31.2%)		114/390 (29.2%)
Serious Adverse Events
	OBSERVATION		ATEZOLIZUMAB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/397 (17.9%)		122/390 (31.3%)
Blood and lymphatic system disorders
Anaemia	0/397 (0%)	0	1/390 (0.3%)	1
Cardiac disorders
Atrial fibrillation	0/397 (0%)	0	2/390 (0.5%)	2
Bradycardia	0/397 (0%)	0	1/390 (0.3%)	1
Cardio-respiratory arrest	1/397 (0.3%)	1	0/390 (0%)	0
Myocardial infarction	0/397 (0%)	0	1/390 (0.3%)	1
Supraventricular tachycardia	0/397 (0%)	0	1/390 (0.3%)	1
Endocrine disorders
Adrenal insufficiency	0/397 (0%)	0	1/390 (0.3%)	1
Hypophysitis	0/397 (0%)	0	1/390 (0.3%)	1
Hypothyroidism	0/397 (0%)	0	1/390 (0.3%)	1
Gastrointestinal disorders
Abdominal pain	2/397 (0.5%)	2	0/390 (0%)	0
Abdominal pain upper	0/397 (0%)	0	1/390 (0.3%)	1
Colitis	0/397 (0%)	0	4/390 (1%)	4
Constipation	2/397 (0.5%)	2	0/390 (0%)	0
Diarrhoea	0/397 (0%)	0	5/390 (1.3%)	5
Enterovesical fistula	1/397 (0.3%)	1	1/390 (0.3%)	1
Gastrointestinal haemorrhage	0/397 (0%)	0	1/390 (0.3%)	1
Hernial eventration	1/397 (0.3%)	1	1/390 (0.3%)	1
Ileus	1/397 (0.3%)	1	1/390 (0.3%)	1
Immune-mediated enterocolitis	0/397 (0%)	0	1/390 (0.3%)	1
Intestinal obstruction	2/397 (0.5%)	2	4/390 (1%)	5
Intestinal perforation	0/397 (0%)	0	2/390 (0.5%)	2
Mechanical ileus	1/397 (0.3%)	1	1/390 (0.3%)	1
Pancreatitis acute	1/397 (0.3%)	1	1/390 (0.3%)	1
Proctalgia	1/397 (0.3%)	1	0/390 (0%)	0
Proctitis	0/397 (0%)	0	1/390 (0.3%)	1
Small intestinal obstruction	2/397 (0.5%)	2	1/390 (0.3%)	1
Small intestine ulcer	0/397 (0%)	0	1/390 (0.3%)	1
Vomiting	1/397 (0.3%)	1	1/390 (0.3%)	1
General disorders
Asthenia	0/397 (0%)	0	1/390 (0.3%)	1
Death	1/397 (0.3%)	1	3/390 (0.8%)	3
Hernia pain	1/397 (0.3%)	1	0/390 (0%)	0
Hyperthermia	0/397 (0%)	0	1/390 (0.3%)	1
Influenza like illness	0/397 (0%)	0	1/390 (0.3%)	1
Lithiasis	0/397 (0%)	0	1/390 (0.3%)	1
Malaise	0/397 (0%)	0	1/390 (0.3%)	1
Pyrexia	4/397 (1%)	4	11/390 (2.8%)	11
Hepatobiliary disorders
Autoimmune hepatitis	0/397 (0%)	0	2/390 (0.5%)	3
Bile duct stone	0/397 (0%)	0	1/390 (0.3%)	1
Cholangitis	0/397 (0%)	0	1/390 (0.3%)	1
Cholecystitis	0/397 (0%)	0	1/390 (0.3%)	1
Hepatic haematoma	0/397 (0%)	0	1/390 (0.3%)	1
Hepatitis	0/397 (0%)	0	1/390 (0.3%)	1
Liver disorder	0/397 (0%)	0	1/390 (0.3%)	1
Immune system disorders
Drug hypersensitivity	0/397 (0%)	0	1/390 (0.3%)	1
Hypersensitivity	0/397 (0%)	0	1/390 (0.3%)	1
Systemic immune activation	0/397 (0%)	0	2/390 (0.5%)	2
Infections and infestations
Abdominal abscess	0/397 (0%)	0	1/390 (0.3%)	1
Bacteraemia	0/397 (0%)	0	1/390 (0.3%)	1
Bacterial sepsis	0/397 (0%)	0	1/390 (0.3%)	1
Cystitis	1/397 (0.3%)	1	0/390 (0%)	0
Diabetic foot infection	0/397 (0%)	0	1/390 (0.3%)	1
Escherichia sepsis	1/397 (0.3%)	1	0/390 (0%)	0
Febrile infection	0/397 (0%)	0	1/390 (0.3%)	1
Infection	1/397 (0.3%)	1	1/390 (0.3%)	1
Kidney infection	1/397 (0.3%)	1	1/390 (0.3%)	1
Lower respiratory tract infection	1/397 (0.3%)	1	1/390 (0.3%)	1
Neuroborreliosis	0/397 (0%)	0	1/390 (0.3%)	1
Osteomyelitis	0/397 (0%)	0	1/390 (0.3%)	1
Pneumonia	2/397 (0.5%)	2	4/390 (1%)	4
Pyelonephritis	9/397 (2.3%)	11	12/390 (3.1%)	16
Pyelonephritis acute	1/397 (0.3%)	1	1/390 (0.3%)	2
Pyelonephritis chronic	0/397 (0%)	0	1/390 (0.3%)	1
Renal abscess	0/397 (0%)	0	1/390 (0.3%)	1
Respiratory tract infection	0/397 (0%)	0	1/390 (0.3%)	1
Sepsis	1/397 (0.3%)	1	3/390 (0.8%)	5
Septic shock	1/397 (0.3%)	1	0/390 (0%)	0
Sinusitis	0/397 (0%)	0	1/390 (0.3%)	1
Upper respiratory tract infection	0/397 (0%)	0	1/390 (0.3%)	1
Urinary tract infection	19/397 (4.8%)	22	30/390 (7.7%)	41
Urinary tract infection bacterial	1/397 (0.3%)	1	1/390 (0.3%)	1
Urosepsis	3/397 (0.8%)	3	1/390 (0.3%)	1
Vascular device infection	0/397 (0%)	0	1/390 (0.3%)	1
Wound infection	0/397 (0%)	0	1/390 (0.3%)	1
Injury, poisoning and procedural complications
Incision site impaired healing	0/397 (0%)	0	1/390 (0.3%)	1
Infusion related reaction	0/397 (0%)	0	2/390 (0.5%)	2
Post procedural haemorrhage	0/397 (0%)	0	1/390 (0.3%)	1
Stoma obstruction	0/397 (0%)	0	1/390 (0.3%)	1
Stomal hernia	1/397 (0.3%)	1	0/390 (0%)	0
Ureteric anastomosis complication	1/397 (0.3%)	1	0/390 (0%)	0
Urostomy complication	1/397 (0.3%)	1	0/390 (0%)	0
Metabolism and nutrition disorders
Acidosis	1/397 (0.3%)	1	1/390 (0.3%)	1
Dehydration	0/397 (0%)	0	1/390 (0.3%)	1
Diabetes mellitus	1/397 (0.3%)	1	1/390 (0.3%)	1
Hypercalcaemia	1/397 (0.3%)	1	0/390 (0%)	0
Hyperglycaemia	2/397 (0.5%)	2	1/390 (0.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/397 (0%)	0	1/390 (0.3%)	1
Arthritis	0/397 (0%)	0	1/390 (0.3%)	1
Groin pain	0/397 (0%)	0	1/390 (0.3%)	1
Musculoskeletal pain	0/397 (0%)	0	1/390 (0.3%)	1
Pain in extremity	0/397 (0%)	0	2/390 (0.5%)	2
Rotator cuff syndrome	1/397 (0.3%)	1	0/390 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric	1/397 (0.3%)	1	0/390 (0%)	0
Gastric cancer	1/397 (0.3%)	1	0/390 (0%)	0
Laryngeal squamous cell carcinoma	1/397 (0.3%)	1	0/390 (0%)	0
Lung adenocarcinoma	0/397 (0%)	0	1/390 (0.3%)	1
Squamous cell carcinoma of lung	1/397 (0.3%)	1	0/390 (0%)	0
Tumour of ampulla of Vater	0/397 (0%)	0	1/390 (0.3%)	1
Nervous system disorders
Cerebral haemorrhage	1/397 (0.3%)	1	0/390 (0%)	0
Cerebrovascular accident	0/397 (0%)	0	1/390 (0.3%)	1
Headache	0/397 (0%)	0	1/390 (0.3%)	1
Immune-mediated neuropathy	0/397 (0%)	0	1/390 (0.3%)	1
Ischaemic stroke	1/397 (0.3%)	1	0/390 (0%)	0
Neuropathy peripheral	0/397 (0%)	0	1/390 (0.3%)	1
Syncope	1/397 (0.3%)	1	0/390 (0%)	0
Product Issues
Device dislocation	1/397 (0.3%)	1	0/390 (0%)	0
Device occlusion	1/397 (0.3%)	1	0/390 (0%)	0
Renal and urinary disorders
Acute kidney injury	4/397 (1%)	4	8/390 (2.1%)	8
Autoimmune nephritis	0/397 (0%)	0	1/390 (0.3%)	1
Dysuria	0/397 (0%)	0	1/390 (0.3%)	1
Hydronephrosis	1/397 (0.3%)	1	1/390 (0.3%)	1
Nephritis	0/397 (0%)	0	1/390 (0.3%)	1
Nephrolithiasis	0/397 (0%)	0	1/390 (0.3%)	3
Renal impairment	0/397 (0%)	0	1/390 (0.3%)	1
Renal injury	0/397 (0%)	0	1/390 (0.3%)	1
Ureteric obstruction	1/397 (0.3%)	2	1/390 (0.3%)	1
Ureteric stenosis	0/397 (0%)	0	1/390 (0.3%)	1
Ureterolithiasis	0/397 (0%)	0	1/390 (0.3%)	1
Urinary retention	1/397 (0.3%)	1	0/390 (0%)	0
Urinary tract obstruction	1/397 (0.3%)	1	2/390 (0.5%)	2
Urinoma	1/397 (0.3%)	1	0/390 (0%)	0
Vesicoureteric reflux	0/397 (0%)	0	1/390 (0.3%)	1
Reproductive system and breast disorders
Female genital tract fistula	2/397 (0.5%)	2	0/390 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/397 (0%)	0	1/390 (0.3%)	1
Asthma	0/397 (0%)	0	1/390 (0.3%)	1
Dyspnoea	1/397 (0.3%)	1	0/390 (0%)	0
Pneumonitis	0/397 (0%)	0	3/390 (0.8%)	3
Pulmonary embolism	5/397 (1.3%)	5	1/390 (0.3%)	1
Skin and subcutaneous tissue disorders
Drug eruption	0/397 (0%)	0	1/390 (0.3%)	1
Rash	0/397 (0%)	0	1/390 (0.3%)	1
Rash maculo-papular	0/397 (0%)	0	1/390 (0.3%)	1
Vascular disorders
Arteriosclerosis	1/397 (0.3%)	1	0/390 (0%)	0
Deep vein thrombosis	3/397 (0.8%)	3	0/390 (0%)	0
Embolism	1/397 (0.3%)	1	0/390 (0%)	0
Hypertension	1/397 (0.3%)	1	0/390 (0%)	0
Hypotension	1/397 (0.3%)	1	0/390 (0%)	0
Lymphocele	0/397 (0%)	0	1/390 (0.3%)	1
Orthostatic hypotension	0/397 (0%)	0	1/390 (0.3%)	1
Other (Not Including Serious) Adverse Events
	OBSERVATION		ATEZOLIZUMAB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	232/397 (58.4%)		324/390 (83.1%)
Blood and lymphatic system disorders
Anaemia	32/397 (8.1%)	34	42/390 (10.8%)	53
Endocrine disorders
Hypothyroidism	0/397 (0%)	0	35/390 (9%)	38
Gastrointestinal disorders
Abdominal pain	29/397 (7.3%)	32	31/390 (7.9%)	39
Constipation	39/397 (9.8%)	40	51/390 (13.1%)	60
Diarrhoea	25/397 (6.3%)	29	81/390 (20.8%)	103
Nausea	20/397 (5%)	21	52/390 (13.3%)	60
Vomiting	14/397 (3.5%)	16	26/390 (6.7%)	34
General disorders
Asthenia	16/397 (4%)	16	35/390 (9%)	41
Chills	7/397 (1.8%)	9	23/390 (5.9%)	25
Fatigue	42/397 (10.6%)	49	89/390 (22.8%)	118
Oedema peripheral	23/397 (5.8%)	26	34/390 (8.7%)	38
Pyrexia	30/397 (7.6%)	43	71/390 (18.2%)	90
Infections and infestations
Upper respiratory tract infection	18/397 (4.5%)	19	21/390 (5.4%)	27
Urinary tract infection	59/397 (14.9%)	84	63/390 (16.2%)	88
Investigations
Alanine aminotransferase increased	7/397 (1.8%)	8	24/390 (6.2%)	32
Aspartate aminotransferase increased	5/397 (1.3%)	6	20/390 (5.1%)	25
Blood alkaline phosphatase increased	8/397 (2%)	8	20/390 (5.1%)	29
Blood creatinine increased	17/397 (4.3%)	20	37/390 (9.5%)	42
Metabolism and nutrition disorders
Decreased appetite	20/397 (5%)	21	45/390 (11.5%)	54
Musculoskeletal and connective tissue disorders
Arthralgia	24/397 (6%)	26	43/390 (11%)	48
Back pain	44/397 (11.1%)	54	26/390 (6.7%)	31
Myalgia	6/397 (1.5%)	8	21/390 (5.4%)	30
Pain in extremity	9/397 (2.3%)	9	22/390 (5.6%)	29
Nervous system disorders
Dizziness	11/397 (2.8%)	11	20/390 (5.1%)	22
Headache	8/397 (2%)	8	35/390 (9%)	39
Respiratory, thoracic and mediastinal disorders
Cough	23/397 (5.8%)	23	47/390 (12.1%)	60
Dyspnoea	7/397 (1.8%)	7	27/390 (6.9%)	33
Skin and subcutaneous tissue disorders
Dry skin	2/397 (0.5%)	2	29/390 (7.4%)	30
Pruritus	10/397 (2.5%)	14	92/390 (23.6%)	113
Rash	5/397 (1.3%)	6	38/390 (9.7%)	48

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.