IMbassador250: A Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Enzalutamide in Participants With Metastatic Castration-Resistant Prostrate Cancer (mCRPC) After Failure of an Androgen Synthesis Inhibitor And Failure of, Ineligibility For, or Refusal of a Taxane Regimen

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03016312
• Collaborator: (none)
• Enrollment: 771
• Locations: 158
• Arms: 2
• Anticipated Duration (Months): 69.1
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This Phase III, multicenter, randomized, open-label study will evaluate the safety and efficacy of atezolizumab (anti-programmed death-ligand 1 [anti-PD-L1] antibody) in combination with enzalutamide compared with enzalutamide alone in participants with mCRPC after failure of an androgen synthesis inhibitor (e.g., abiraterone) and failure of, ineligibility for, or refusal of a taxane regimen. Participants will be randomized to one of the two treatment arms (atezolizumab in combination with enzalutamide, and enzalutamide alone) in a 1:1 ratio (experimental to control arm) in global randomized phase. Participants will receive treatment until investigator-assessed confirmed radiographic disease progression per Prostate Cancer Working Group 3 (PCWG3) criteria or unacceptable toxicity.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms, Castration-Resistant	Drug: Atezolizumab; Drug: Enzalutamide	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 771 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Enzalutamide Versus Enzalutamide Alone in Patients With Metastatic Castration-Resistant Prostate Cancer After Failure of an Androgen Synthesis Inhibitor and Failure of, Ineligibility for, or Refusal of a Taxane Regimen
• Actual Study Start Date: Jan 10, 2017
• Anticipated Primary Completion Date: Oct 15, 2022
• Anticipated Study Completion Date: Oct 15, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Atezolizumab + Enzalutamide Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).	Drug: Atezolizumab; Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg), intravenous (IV) infusion on Day 1 of each 21-day cycle.; Other Names: Tecentriq® ; Drug: Enzalutamide; Enzalutamide capsules will be administered orally at a dose of 160 mg daily.; Other Names: Xtandi®
Active Comparator: Enzalutamide Participants will receive enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).	Drug: Enzalutamide; Enzalutamide capsules will be administered orally at a dose of 160 mg daily.; Other Names: Xtandi®

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [Baseline until death from any cause (up to approximately 42 months)]

   Overall Survival is defined as the time from randomization to death from any cause.

Secondary Outcome Measures

1. Percentage of Participants Who Survived at Month 12 and 24 [Months 12, 24]

   OS (Overall Survival is defined as the time from randomization to death from any cause) probability at 12 and 24 months

2. Time to First Symptomatic Skeletal Event (SSE) [Baseline up to end of study (up to approximately 42 months)]

   An SSE is defined as external beam radiation therapy to relieve skeletal symptoms (including initiation of radium-223 dichloride or other types of radionuclide therapy to treat symptoms of bone metastases), new symptomatic pathologic bone fracture, clinically apparent occurrence of spinal cord compression, or tumor related orthopedic surgical intervention.

3. Radiographic Progression-Free Survival (rPFS), as Assessed by the Investigator and Adapted From the PCWG3 Criteria [Baseline until disease progression or death from any cause (up to approximately 42 months)]

   rPFS is defined as the time from randomization to the earliest occurrence of one of the following: A participant is considered to have progressed by bone scan if: The first bone scan with ≥2 new lesions compared to baseline is observed < 12 weeks from randomization and is confirmed by a second bone scan taken ≥6 weeks later showing ≥2 additional new lesions (a total of ≥4 new lesions compared to baseline); the date of progression is the date of the first post-treatment scan, OR After the first post-treatment scan, ≥2 new lesions are observed relative to the first post-treatment scan, which is confirmed on a subsequent scan ≥6 weeks later; the date of progression is the date of the post-treatment scan when ≥2 new lesions were first documented. Progression of soft tissue lesions, as defined per PCWG3 modified RECIST v1.1 Death from any cause

4. Percentage of Participants Who Are Radiographic Progression-Free, as Assessed by the Investigator and Adapted From the PCWG3 Criteria [Months 6, 12]

   rPFS is defined as the time from randomization to the earliest occurrence of one of the following: A participant is considered to have progressed by bone scan if: The first bone scan with ≥2 new lesions compared to baseline is observed < 12 weeks from randomization and is confirmed by a second bone scan taken ≥6 weeks later showing ≥2 additional new lesions (a total of ≥4 new lesions compared to baseline); the date of progression is the date of the first post-treatment scan, OR After the first post-treatment scan, ≥2 new lesions are observed relative to the first post-treatment scan, which is confirmed on a subsequent scan ≥6 weeks later; the date of progression is the date of the post-treatment scan when ≥2 new lesions were first documented. Progression of soft tissue lesions, as defined per PCWG3 modified RECIST v1.1 Death from any cause

5. Percentage of Participants With Greater Than (>) 50 Percent (%) Decrease in Prostate-Specific Antigen (PSA) From Baseline [Baseline until disease progression (up to approximately 42 months)]

   PSA response rate, defined as a > 50% decrease in PSA from baseline that is confirmed after ≥ 3 weeks by a consecutive confirmatory PSA measurement

6. Time to PSA Progression, Assessed as Per PCWG3 Criteria [Baseline until disease progression (up to approximately 42 months)]

   In participants with no PSA decline from baseline, PSA progression is defined as a ≥25% increase and an absolute increase of ≥2 ng/mL above the baseline value, ≥12 weeks after baseline. In participants with an initial PSA decline from baseline, PSA progression is defined as a ≥25% increase and an absolute increase of ≥2 ng/mL above the nadir value, which is confirmed by a consecutive second value obtained ≥3 weeks later.

7. Percentage of Participant With Objective Response, as Determined by the Investigator Through Use of PCWG3 Criteria [Baseline until disease progression or death from any cause (up to approximately 42 months)]

   Objective response rate in soft tissue lesions, defined as the percentage of participants with either a CR or PR on two consecutive occasions ≥ 6 weeks apart, as determined by the investigator through use of PCWG3 criteria

8. Percentage of Participants With Adverse Events [Baseline up to end of study (up to approximately 42 month]

   Verbatim description of adverse events will be coded to MedDRA preferred terms and graded according to NCI CTCAE v4.0.

9. Minimum Observed Serum Concentration (Cmin) of Atezolizumab [Pre-infusion (0 hour[hr]) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); treatment discontinuation visit, 120 days after last dose (up to approximately 42 months)]

   Atezolizumab serum concentration data (minimum [Cmin]) will be reported and summarized for each cycle where collected as appropriate.

10. Maximum Observed Serum Concentration (Cmax) of Atezolizumab [Pre-infusion (0 hr) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); 0.5 hr post-infusion (infusion duration: 60 minutes [min]) on Day 1 Cycle 1; treatment discontinuation visit, 120 days after last dose (up to approximately 42 months)]

    Atezolizumab serum concentration data (maximum [Cmax]) will be reported and summarized for each cycle where collected as appropriate.

11. Plasma Concentration of Enzalutamide [Predose (0 hr) and 1 hr postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (within 1 hr) on Day 1 Cycle 8]

    Plasma concentrations of Enzalutamide will be reported and summarized using descriptive statistics for each cycle and treatment arm, as appropriate.

12. Plasma Concentration of N-Desmethyl Enzalutamide [Predose (0 hr) and 1 hr postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (within 1 hr) on Day 1 Cycle 8]

    Plasma concentrations of N-desmethyl enzalutamide will be reported and summarized using descriptive statistics for each cycle and treatment arm, as appropriate.

13. Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab [Predose (0 hr) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); at atezolizumab discontinuation visit (30 days after last dose); 120 days after last dose of atezolizumab; up to 42 months]

    The numbers and proportions of ATA-positive participants and ATA-negative participants at baseline (baseline prevalence) and after baseline (post-baseline incidence) will be summarized by treatment group.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Life expectancy greater than or equal to (>/=) 3 months

• Histologically confirmed adenocarcinoma of the prostate

• Known castrate-resistant disease with serum testosterone level less than or equal to (</=) 50 nanograms per deciliter (ng/dL) with prior surgical castration or ongoing androgen deprivation for the duration of the study

• Progressive disease prior to screening by PSA or imaging per PCWG3 criteria during or following the direct prior line of therapy in the setting of medical or surgical castration

• One prior regimen/line of a taxane-containing regimen for mCRPC or refusal or ineligibility of a taxane-containing regimen

• Progression on a prior regimen/line of an androgen synthesis inhibitor for prostate cancer

• Availability of a representative tumor specimen from a site not previously irradiated that is suitable for determination of programmed death-ligand 1 (PD-L1) status via central testing

• Adequate hematologic and end organ function

Exclusion Criteria:

• Prior treatment with enzalutamide or any other newer hormonal androgen receptor inhibitor (e.g., apalutamide, ODM-201)

• Treatment with any approved anti-cancer therapy, including chemotherapy, immunotherapy, radiopharmaceutical or hormonal therapy (with the exception of abiraterone), within 4 weeks prior to initiation of study treatment

• Treatment with abiraterone within 2 weeks prior to study treatment

• Structurally unstable bone lesions suggesting impending fracture

• Known or suspected brain metastasis or active leptomeningeal disease

• Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study

• Active or history of autoimmune disease or immune deficiency

• Prior allogeneic stem cell or solid organ transplantation

• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan

• Positive human immunodeficiency virus (HIV) test, active tuberculosis, active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

• Prior treatment with cluster of differentiation (CD)137 agonists or immune checkpoint blockade therapies, including anti Cytotoxic T Lymphocyte-Associated 4 (CTLA4), anti-programmed death 1 (PD-1), and anti-PD-L1 therapeutic antibodies

• Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is shorter, prior to initiation of study treatment

• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study

• History of seizure or any condition that may predispose to seizure within 12 months prior to study treatment, including history of unexplained loss of consciousness or transient ischemic attack

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Medical Grp Inc.	Duarte	California	United States	91010
2	University of California San Diego	La Jolla	California	United States	92093
3	Kaiser Permanente San Diego - Los Angeles	Los Angeles	California	United States	90027
4	UC Irvine Medical Center	Orange	California	United States	92868
5	Pacific Hematology Oncology Associates	San Francisco	California	United States	94115
6	University of Colorado; Division of Medical Oncology	Aurora	Colorado	United States	80021
7	Yale School of Medicine	New Haven	Connecticut	United States	06510
8	Stamford Hospital; BCC, MOHR	Stamford	Connecticut	United States	06904
9	Lynn Cancer Institute/Boca Raton Regional Hospital	Boca Raton	Florida	United States	33486
10	SCRI Florida Cancer Specialists South	Fort Myers	Florida	United States	33916
11	Miami Cancer Institute of Baptist Health, Inc.	Miami	Florida	United States	33176
12	Florida Cancer Specialist, North Region	Saint Petersburg	Florida	United States	33705
13	Investigative Clin Rsch of IN	Indianapolis	Indiana	United States	46260
14	Associates in Oncology/Hematology P.C.	Rockville	Maryland	United States	20850
15	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
16	Karmanos Cancer Institute..	Detroit	Michigan	United States	48201
17	Nebraska Cancer Specialists; Oncology Hematology West, PC	Omaha	Nebraska	United States	68130
18	Urology Cancer Center & GU Research Network	Omaha	Nebraska	United States	68130
19	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89128
20	MSKCC at Basking Ridge	Basking Ridge	New Jersey	United States	07920
21	New York Oncology Hematology, P.C.	Albany	New York	United States	12208
22	Columbia University Medical Center	New York	New York	United States	10032
23	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
24	Oncology Hematology Care, Inc.	Cincinnati	Ohio	United States	45230
25	James Cancer Hospital;Solove Research Institute	Columbus	Ohio	United States	43210
26	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
27	Allegheny Cancer Center	Pittsburgh	Pennsylvania	United States	15212
28	University of Pittsburgh Cancer Institute; Division of Medical Oncology	Pittsburgh	Pennsylvania	United States	15232
29	Miriam Hospital	Providence	Rhode Island	United States	02906
30	Charleston Oncology, P .A	Charleston	South Carolina	United States	29414
31	Carolina Urologic Research Center	Myrtle Beach	South Carolina	United States	29572
32	SCRI Tennessee Oncology Chattanooga	Chattanooga	Tennessee	United States	37404
33	Texas Oncology Cancer Center	Austin	Texas	United States	78731
34	Texas Oncology - Methodist Dallas Cancer Center	Dallas	Texas	United States	75203
35	Texas Oncology, P.A. - Fort Worth	Fort Worth	Texas	United States	76104
36	Texas Oncology - Memorial City	Houston	Texas	United States	77024
37	Texas Oncology-Tyler	Irving	Texas	United States	75063
38	Virginia Cancer Specialists - Alexandria	Alexandria	Virginia	United States	22304
39	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
40	Eastern Health; Cancer Services	Box Hill	New South Wales	Australia	3128
41	Concord Repatriation General Hospital; Concord Cancer Centre	Concord	New South Wales	Australia	2139
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	Adelaide Cancer Centre	Kurralta Park	South Australia	Australia	5037
45	Monash Medical Centre; Oncology	Clayton	Victoria	Australia	3168
46	LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie	Graz		Austria	8036
47	Ordensklinikum Linz Elisabethinen; Abteilung für Urologie und Andrologie	Linz		Austria	4020
48	Medizinische Universität Wien; Universitätsklinik für Urologie	Wien		Austria	1090
49	Onze Lieve Vrouwziekenhuis Aalst	Aalst		Belgium	9300
50	UZ Gent	Gent		Belgium	9000
51	CHU Sart-Tilman	Liège		Belgium	4000
52	Tom Baker Cancer Centre-Calgary	Calgary	Alberta	Canada	T2N 4N2
53	Kingston General Hospital	Kingston	Ontario	Canada	K7L 2V7
54	Lakeridge Health Oshawa; Oncology	Oshawa	Ontario	Canada	L1G 2B9
55	Princess Margaret Cancer Center	Toronto	Ontario	Canada	M5G 1Z5
56	Hopital Charles Lemoyne; Centre Integre de Lutte Contre Le Cancer de La Monteregie	Greenfield Park	Quebec	Canada	J4V 2H1
57	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
58	Centre Hospitalier Universitaire de Sherbrooke - Hopital Fleurimont	Sherbrooke	Quebec	Canada	J1H 5N4
59	CHU de Québec - Université Laval - Hôtel-Dieu de Québec	Quebec		Canada	G1J 1Z4
60	Friendship Hospital, Capital Medical University	Beijing		China	100050
61	Jiangsu Cancer Hospital	Nanjing City		China	211100
62	Fudan University Shanghai Cancer Center	Shanghai City		China	200120
63	Zhongshan Hospital Fudan University	Shanghai		China	200032
64	Masarykuv onkologicky ustav	Brno		Czechia	656 53
65	Fakultni nemocnice u sv. Anny v Brne	Brno		Czechia	656 91
66	Thomayerova nemocnice	Praha 4 - Krc		Czechia	140 59
67	Aalborg Universitetshospital, Klinik Kirurgi-Kræft, Onkologisk afd.	Aalborg		Denmark	9000
68	Herlev Hospital; Afdeling for Kræftbehandling	Herlev		Denmark	2730
69	Odense Universitetshospital, Onkologisk Afdeling R	Odense C		Denmark	5000
70	Institut Sainte-Catherine; Oncologie	Avignon		France	84082
71	Centre Francois Baclesse; Oncologie	Caen		France	14076
72	Hopital Louis Pasteur; Medecine B	Colmar		France	68024
73	Centre Oscar Lambret; Chir Cancerologie General	Lille		France	59000
74	Clinique Chenieux; Oncology	Limoges		France	87039
75	Hopital Saint Louis, Service D Oncologie Medicale	Paris		France	75475
76	Hopital d'Instruction des Armees de Begin	Saint-Mande		France	94160
77	Institut Claudius Regaud; Departement Oncologie Medicale	Toulouse		France	31059
78	Institut Gustave Roussy	Villejuif		France	94805
79	Universitätsklinikum Freiburg; Chirurgische Klinik; Abteilung Urologie	Freiburg		Germany	79106
80	Medizinische Hochschule Hannover; Klinik für Urologie und Onkologische Urologie	Hannover		Germany	30625
81	Universitätsklinikum Münster, Klinik für Urologie und Kinderurologie	Münster		Germany	48149
82	Universitätsklinikum Tübingen; Klinik für Urologie	Tübingen		Germany	72076
83	Urologisches Zentrum Euregio; Würselen, Urologische Praxis am Wasserturm	Würselen		Germany	52146
84	Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine	Athens		Greece	115 22
85	Alexandras Hospital; Dept. of Clin. Therapeutics, Athens Uni School of Medicine	Athens		Greece	115 28
86	Athens Medical Center; Dept. of Oncology	Athens		Greece	151 25
87	IASO General Hospital of Athens	Athens		Greece	155 62
88	Agioi Anargyroi Cancer Hospital; 2Nd Oncology Dept.	Kifisia		Greece	145 64
89	University Hospital of Patras Medical Oncology	Patras		Greece	265 04
90	Papageorgiou General Hospital; Medical Oncology	Thessaloniki		Greece	564 29
91	Semmelwies University of Medicine; Urology Dept.	Budapest		Hungary	1082
92	Orszagos Onkologiai Intezet; "C" Belgyógyászati-Onkológiai és Klinikai Farmakológiai Osztály	Budapest		Hungary	1122
93	Debreceni Egyetem Klinikai Kozpont ; Department of Oncology	Debrecen		Hungary	4032
94	ISTITUTO NAZIONALE TUMORI IRCCS FONDAZIONE G. PASCALE; Dipartimento Uro-Ginecologico	Napoli	Campania	Italy	80131
95	A.O. Universitaria Policlinico Di Modena; Oncologia	Modena	Emilia-Romagna	Italy	41100
96	Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica	Roma	Lazio	Italy	00152
97	IRCCS AOU San Martino - IST; Oncologia Medica 1	Genova	Liguria	Italy	16132
98	A.O. Istituti Ospitalieri - Cremona; S.C. Oncologia	Cremona	Lombardia	Italy	26100
99	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2	Milano	Lombardia	Italy	20133
100	Irccs Istituto Europeo Di Oncologia (IEO); Cure Mediche	Milano	Lombardia	Italy	20141
101	Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica	Bari	Puglia	Italy	70124
102	IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia	San Giovanni Rotondo	Puglia	Italy	71013
103	Ospedale Area Aretina Nord; U.O.C. Oncologia	Arezzo	Toscana	Italy	52100
104	IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima	Padova	Veneto	Italy	35128
105	Nagoya City University Hospital	Aichi		Japan	467-8602
106	National Cancer Center East	Chiba		Japan	277-8577
107	Toho University Sakura Medical Center	Chiba		Japan	285-8741
108	Kyushu University Hospital	Fukuoka		Japan	812-8582
109	National Hospital Organization Hokkaido Cancer Center	Hokkaido		Japan	003-0804
110	Yokohama City University Medical Center	Kanagawa		Japan	232-0024
111	Kitasato University Hospital	Kanagawa		Japan	252-0375
112	University Hospital Kyoto Prefectural University of Medicine	Kyoto		Japan	602-8566
113	Nara Medical University Hospital	Nara		Japan	634-8522
114	Niigata University Medical & Dental Hospital	Niigata		Japan	951-8520
115	Kansai Medical University Hospital	Osaka		Japan	573-1191
116	Toranomon Hospital	Tokyo		Japan	105-8470
117	The Jikei University Hospital	Tokyo		Japan	105-8471
118	Nippon Medical School Hospital	Tokyo		Japan	113-8603
119	National Cancer Center	Goyang-si		Korea, Republic of	10408
120	Seoul National University Hospital	Seoul		Korea, Republic of	03080
121	Asan Medical Center	Seoul		Korea, Republic of	05505
122	Samsung Medical Center	Seoul		Korea, Republic of	06351
123	Medical University of Bialystok; Oncology clinic	Bialystok		Poland	15-027
124	Przychodnia Lekarska KOMED, Roman Karaszewski	Konin		Poland	62-500
125	Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii	Kraków		Poland	30-688
126	SPZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarawskiego	Opole		Poland	45-060
127	Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii	Otwock		Poland	05-400
128	Szpital Sw. Elzbiety - Mokotowskie Centrum Medyczne Sp. z o.o.	Warszawa		Poland	02-616
129	Wojewodzki Szpital; Specjalistyczny ul.	Wroclaw		Poland	51-124
130	Woj. Wielospec. Centrum Onkologii i Traumatologii	Łódź		Poland	93-513
131	SBEI HPE "The First St.Petersburg State Medical University n.a. acad. I.P.Pavlova"of MoH of RF	Sankt-peterburg	Leningrad	Russian Federation	197022
132	Russian Scientific Center of Roentgenoradiology	Moscow		Russian Federation	117997
133	P.A. Herzen Oncological Inst. ; Oncology	Moscow		Russian Federation	125284
134	Institut Catala d´Oncologia Hospital Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
135	Insititut Catala D'Oncologia	Hospitalet de Llobregat	Barcelona	Spain	08908
136	Corporacio Sanitaria Parc Tauli; Servicio de Oncologia	Sabadell	Barcelona	Spain	8208
137	Hospital Universitario Reina Sofia; Servicio de Oncologia	Córdoba	Cordoba	Spain	14004
138	Clinica Universitaria de Navarra; Servicio de Oncologia	Pamplona	Navarra	Spain	31008
139	Hospital Universitari Vall d'Hebron; Oncology	Barcelona		Spain	08035
140	Hospital Clínic i Provincial; Servicio de Oncología	Barcelona		Spain	08036
141	Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia	Barcelona		Spain	08041
142	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid		Spain	28034
143	Hospital Clinico San Carlos; Servicio de Oncologia	Madrid		Spain	28040
144	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid		Spain	28041
145	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga		Spain	29010
146	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla		Spain	41013
147	Inselspital Bern; Universitätsklinik für medizinische Onkologie	Bern		Switzerland	3010
148	Kantonsspital St. Gallen; Onkologie/Hämatologie	St. Gallen		Switzerland	9007
149	Taichung Veterans General Hospital; Division of Urology	Taichung		Taiwan	407
150	National Taiwan University Hospital, Department of Urology	Taipei		Taiwan	10048
151	TAIPEI VETERANS GENERAL HOSPITAL, Urology	Taipei		Taiwan	11217
152	Chang Gung Memorial Hospital-LinKou; Urology	Taoyuan		Taiwan	333
153	Royal Blackburn Hospital	Blackburn		United Kingdom	BB2 3HH
154	Leicester Royal Infirmary	Leicester		United Kingdom	LE1 5WW
155	Barts and the London NHS Trust.	London		United Kingdom	EC1A 7BE
156	Sarah Cannon Research Institute	London		United Kingdom	W1G 6AD
157	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX
158	Royal Marsden Hospital; Institute of Cancer Research	Sutton		United Kingdom	SM2 5PT

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 14, 2020

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03016312
• Other Study ID Numbers: CO39385; 2016-003092-22
• First Posted: Jan 10, 2017
• Last Update Posted: Aug 5, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Atezolizumab

Study Results

Participant Flow

Arm/Group Title	Atezolizumab + Enzalutamide	Enzalutamide
Arm/Group Description	Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).	Participants will receive enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).
Period Title: Overall Study
STARTED	391	380
COMPLETED	150	162
NOT COMPLETED	241	218

Baseline Characteristics

Arm/Group Title	Atezolizumab + Enzalutamide	Enzalutamide	Total
Arm/Group Description	Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).	Participants will receive enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).	Total of all reporting groups
Overall Participants	391	380	771
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	101 25.8%	90 23.7%	191 24.8%
>=65 years	290 74.2%	290 76.3%	580 75.2%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	70.3 (8.3)	70.6 (8.5)	70.4 (8.4)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	391 100%	380 100%	771 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	18 4.6%	11 2.9%	29 3.8%
Not Hispanic or Latino	349 89.3%	345 90.8%	694 90%
Unknown or Not Reported	24 6.1%	24 6.3%	48 6.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.3%	1 0.1%
Asian	71 18.2%	65 17.1%	136 17.6%
Native Hawaiian or Other Pacific Islander	1 0.3%	0 0%	1 0.1%
Black or African American	8 2%	7 1.8%	15 1.9%
White	290 74.2%	287 75.5%	577 74.8%
More than one race	2 0.5%	0 0%	2 0.3%
Unknown or Not Reported	19 4.9%	20 5.3%	39 5.1%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	Overall Survival is defined as the time from randomization to death from any cause.
Time Frame	Baseline until death from any cause (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population is defined as all randomized participants regardless of whether the assigned study treatment was received. For efficacy analyses, participants were analyzed according to their randomized treatment assignment. Here, "Number Analyzed" refers to number of participants from whom data was collected and analyzed.

Arm/Group Title	Atezolizumab + Enzalutamide	Enzalutamide
Arm/Group Description	Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).	Participants will receive enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).
Measure Participants	379	380
Median (95% Confidence Interval) [Months]	15.2	16.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab + Enzalutamide, Enzalutamide
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0940
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.184
	Confidence Interval	(2-Sided) 95%; 0.971 to 1.445
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab + Enzalutamide, Enzalutamide
	Comments	Stratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2786
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.118
	Confidence Interval	(2-Sided) 95%; 0.913 to 1.370
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants Who Survived at Month 12 and 24
Description	OS (Overall Survival is defined as the time from randomization to death from any cause) probability at 12 and 24 months
Time Frame	Months 12, 24

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population is defined as all randomized participants regardless of whether the assigned study treatment was received. For efficacy analyses, participants were analyzed according to their randomized treatment assignment. Here, "Number Analyzed" refers to number of participants from whom data was collected and analyzed.

Arm/Group Title	Atezolizumab + Enzalutamide	Enzalutamide
Arm/Group Description	Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).	Participants will receive enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).
Measure Participants	379	380
6 Months	85.12 21.8%	85.32 22.5%
12 Months	60.61 15.5%	64.65 17%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab + Enzalutamide, Enzalutamide
	Comments	Difference in Event Free Rate - 6 months
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9391
	Comments
	Method	z-test
	Comments
Method of Estimation	Estimation Parameter	Difference in Event Free Rate
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -5.38 to 4.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab + Enzalutamide, Enzalutamide
	Comments	Difference in Event Free Rate - 12 months
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2706
	Comments
	Method	z-test
	Comments
Method of Estimation	Estimation Parameter	Difference in Event Free Rate
	Estimated Value	-4.03
	Confidence Interval	(2-Sided) 95%; -11.21 to 3.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Time to First Symptomatic Skeletal Event (SSE)
Description	An SSE is defined as external beam radiation therapy to relieve skeletal symptoms (including initiation of radium-223 dichloride or other types of radionuclide therapy to treat symptoms of bone metastases), new symptomatic pathologic bone fracture, clinically apparent occurrence of spinal cord compression, or tumor related orthopedic surgical intervention.
Time Frame	Baseline up to end of study (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population is defined as all randomized participants regardless of whether the assigned study treatment was received. For efficacy analyses, participants were analyzed according to their randomized treatment assignment. Here, "Number Analyzed" refers to number of participants from whom data was collected and analyzed.

Arm/Group Title	Atezolizumab + Enzalutamide	Enzalutamide
Arm/Group Description	Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).	Participants will receive enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).
Measure Participants	379	380
Median (95% Confidence Interval) [Months]	24.1	24.9

4. Secondary Outcome

Title	Radiographic Progression-Free Survival (rPFS), as Assessed by the Investigator and Adapted From the PCWG3 Criteria
Description	rPFS is defined as the time from randomization to the earliest occurrence of one of the following: A participant is considered to have progressed by bone scan if: The first bone scan with ≥2 new lesions compared to baseline is observed < 12 weeks from randomization and is confirmed by a second bone scan taken ≥6 weeks later showing ≥2 additional new lesions (a total of ≥4 new lesions compared to baseline); the date of progression is the date of the first post-treatment scan, OR After the first post-treatment scan, ≥2 new lesions are observed relative to the first post-treatment scan, which is confirmed on a subsequent scan ≥6 weeks later; the date of progression is the date of the post-treatment scan when ≥2 new lesions were first documented. Progression of soft tissue lesions, as defined per PCWG3 modified RECIST v1.1 Death from any cause
Time Frame	Baseline until disease progression or death from any cause (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population is defined as all randomized participants regardless of whether the assigned study treatment was received. For efficacy analyses, participants were analyzed according to their randomized treatment assignment. Here, "Number Analyzed" refers to number of participants from whom data was collected and analyzed.

Arm/Group Title	Atezolizumab + Enzalutamide	Enzalutamide
Arm/Group Description	Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).	Participants will receive enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).
Measure Participants	379	380
Median (95% Confidence Interval) [Months]	4.2	4.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab + Enzalutamide, Enzalutamide
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3157
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.917
	Confidence Interval	(2-Sided) 95%; 0.775 to 1.086
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab + Enzalutamide, Enzalutamide
	Comments	Stratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2366
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.899
	Confidence Interval	(2-Sided) 95%; 0.754 to 1.072
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants Who Are Radiographic Progression-Free, as Assessed by the Investigator and Adapted From the PCWG3 Criteria
Description	rPFS is defined as the time from randomization to the earliest occurrence of one of the following: A participant is considered to have progressed by bone scan if: The first bone scan with ≥2 new lesions compared to baseline is observed < 12 weeks from randomization and is confirmed by a second bone scan taken ≥6 weeks later showing ≥2 additional new lesions (a total of ≥4 new lesions compared to baseline); the date of progression is the date of the first post-treatment scan, OR After the first post-treatment scan, ≥2 new lesions are observed relative to the first post-treatment scan, which is confirmed on a subsequent scan ≥6 weeks later; the date of progression is the date of the post-treatment scan when ≥2 new lesions were first documented. Progression of soft tissue lesions, as defined per PCWG3 modified RECIST v1.1 Death from any cause
Time Frame	Months 6, 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population is defined as all randomized participants regardless of whether the assigned study treatment was received. For efficacy analyses, participants were analyzed according to their randomized treatment assignment. Here, "Number Analyzed" refers to number of participants from whom data was collected and analyzed.

Arm/Group Title	Atezolizumab + Enzalutamide	Enzalutamide
Arm/Group Description	Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).	Participants will receive enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).
Measure Participants	379	380
6 months	41.84 10.7%	39.64 10.4%
12 months	14.89 3.8%	13.45 3.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab + Enzalutamide, Enzalutamide
	Comments	Difference in Event Free Rate - 6 months
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5959
	Comments
	Method	z-test
	Comments
Method of Estimation	Estimation Parameter	Difference in Event Free Rate
	Estimated Value	2.21
	Confidence Interval	(2-Sided) 95%; -5.95 to 10.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab + Enzalutamide, Enzalutamide
	Comments	Difference in Event Free Rate - 12 months
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6262
	Comments
	Method	z-test
	Comments
Method of Estimation	Estimation Parameter	Difference in Event Free Rate
	Estimated Value	1.44
	Confidence Interval	(2-Sided) 95%; -4.35 to 7.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With Greater Than (>) 50 Percent (%) Decrease in Prostate-Specific Antigen (PSA) From Baseline
Description	PSA response rate, defined as a > 50% decrease in PSA from baseline that is confirmed after ≥ 3 weeks by a consecutive confirmatory PSA measurement
Time Frame	Baseline until disease progression (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population is defined as all randomized participants regardless of whether the assigned study treatment was received. For efficacy analyses, participants were analyzed according to their randomized treatment assignment. Here, "Number Analyzed" refers to number of participants from whom data was collected and analyzed.

Arm/Group Title	Atezolizumab + Enzalutamide	Enzalutamide
Arm/Group Description	Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).	Participants will receive enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).
Measure Participants	379	380
Number (95% Confidence Interval) [Percentage of Participants]	25.9 6.6%	24.2 6.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab + Enzalutamide, Enzalutamide
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in 50% Decrease Response Rate
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 2%; -4.5 to 7.8
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Odds Ratio: 1.1 95%CI: 0.8, 1.5

7. Secondary Outcome

Title	Time to PSA Progression, Assessed as Per PCWG3 Criteria
Description	In participants with no PSA decline from baseline, PSA progression is defined as a ≥25% increase and an absolute increase of ≥2 ng/mL above the baseline value, ≥12 weeks after baseline. In participants with an initial PSA decline from baseline, PSA progression is defined as a ≥25% increase and an absolute increase of ≥2 ng/mL above the nadir value, which is confirmed by a consecutive second value obtained ≥3 weeks later.
Time Frame	Baseline until disease progression (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population is defined as all randomized participants regardless of whether the assigned study treatment was received. For efficacy analyses, participants were analyzed according to their randomized treatment assignment. Here, "Number Analyzed" refers to number of participants in the ITT population with measurable soft tissue lesions at baseline.

Arm/Group Title	Atezolizumab + Enzalutamide	Enzalutamide
Arm/Group Description	Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).	Participants will receive enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).
Measure Participants	379	380
Median (95% Confidence Interval) [Months]	2.8	2.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab + Enzalutamide, Enzalutamide
	Comments	Unstratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5359
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.055
	Confidence Interval	(2-Sided) 95%; 0.890 to 1.251
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Atezolizumab + Enzalutamide, Enzalutamide
	Comments	Stratified Analysis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6857
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.037
	Confidence Interval	(2-Sided) 95%; 0.869 to 1.238
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participant With Objective Response, as Determined by the Investigator Through Use of PCWG3 Criteria
Description	Objective response rate in soft tissue lesions, defined as the percentage of participants with either a CR or PR on two consecutive occasions ≥ 6 weeks apart, as determined by the investigator through use of PCWG3 criteria
Time Frame	Baseline until disease progression or death from any cause (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

Participants were classified as missing or unevaluable if no post-baseline response assessments were available or all post-baseline response baseline assessments were unevaluable. Responders had to have a CR or PR on two consecutive occasions at least 6 weeks apart.

Arm/Group Title	Atezolizumab + Enzalutamide	Enzalutamide
Arm/Group Description	Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).	Participants will receive enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).
Measure Participants	131	135
Number (95% Confidence Interval) [Percentage of Participants]	13.7 3.5%	7.4 1.9%

9. Secondary Outcome

Title	Percentage of Participants With Adverse Events
Description	Verbatim description of adverse events will be coded to MedDRA preferred terms and graded according to NCI CTCAE v4.0.
Time Frame	Baseline up to end of study (up to approximately 42 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Minimum Observed Serum Concentration (Cmin) of Atezolizumab
Description	Atezolizumab serum concentration data (minimum [Cmin]) will be reported and summarized for each cycle where collected as appropriate.
Time Frame	Pre-infusion (0 hour[hr]) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); treatment discontinuation visit, 120 days after last dose (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Maximum Observed Serum Concentration (Cmax) of Atezolizumab
Description	Atezolizumab serum concentration data (maximum [Cmax]) will be reported and summarized for each cycle where collected as appropriate.
Time Frame	Pre-infusion (0 hr) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); 0.5 hr post-infusion (infusion duration: 60 minutes [min]) on Day 1 Cycle 1; treatment discontinuation visit, 120 days after last dose (up to approximately 42 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Plasma Concentration of Enzalutamide
Description	Plasma concentrations of Enzalutamide will be reported and summarized using descriptive statistics for each cycle and treatment arm, as appropriate.
Time Frame	Predose (0 hr) and 1 hr postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (within 1 hr) on Day 1 Cycle 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Secondary Outcome

Title	Plasma Concentration of N-Desmethyl Enzalutamide
Description	Plasma concentrations of N-desmethyl enzalutamide will be reported and summarized using descriptive statistics for each cycle and treatment arm, as appropriate.
Time Frame	Predose (0 hr) and 1 hr postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (within 1 hr) on Day 1 Cycle 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Secondary Outcome

Title	Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
Description	The numbers and proportions of ATA-positive participants and ATA-negative participants at baseline (baseline prevalence) and after baseline (post-baseline incidence) will be summarized by treatment group.
Time Frame	Predose (0 hr) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); at atezolizumab discontinuation visit (30 days after last dose); 120 days after last dose of atezolizumab; up to 42 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Baseline to primary completion date (up to 2 years 2 months, cut off date: June-24-2019)
Arm/Group Title	Atezolizumab + Enzalutamide		Enzalutamide
Arm/Group Description	Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).		Participants will receive enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).
All Cause Mortality
	Atezolizumab + Enzalutamide		Enzalutamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	216/386 (56%)		180/376 (47.9%)
Serious Adverse Events
	Atezolizumab + Enzalutamide		Enzalutamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	140/386 (36.3%)		83/376 (22.1%)
Blood and lymphatic system disorders
Anaemia	9/386 (2.3%)	11	11/376 (2.9%)	15
Bone marrow failure	1/386 (0.3%)	1	0/376 (0%)	0
Disseminated intravascular coagulation	1/386 (0.3%)	1	0/376 (0%)	0
Febrile neutropenia	0/386 (0%)	0	1/376 (0.3%)	1
Heparin-induced thrombocytopenia	1/386 (0.3%)	1	0/376 (0%)	0
Leukopenia	1/386 (0.3%)	1	0/376 (0%)	0
Neutropenia	1/386 (0.3%)	1	0/376 (0%)	0
Cardiac disorders
Acute coronary syndrome	0/386 (0%)	0	1/376 (0.3%)	1
Acute myocardial infarction	0/386 (0%)	0	1/376 (0.3%)	1
Arrhythmia	1/386 (0.3%)	1	0/376 (0%)	0
Atrial fibrillation	1/386 (0.3%)	1	2/376 (0.5%)	2
Atrial flutter	1/386 (0.3%)	1	0/376 (0%)	0
Autoimmune myocarditis	1/386 (0.3%)	1	0/376 (0%)	0
Cardiac arrest	1/386 (0.3%)	1	0/376 (0%)	0
Cardiac disorder	0/386 (0%)	0	1/376 (0.3%)	1
Cardiac failure	4/386 (1%)	4	2/376 (0.5%)	4
Cardiac failure congestive	1/386 (0.3%)	2	0/376 (0%)	0
Cardiopulmonary failure	1/386 (0.3%)	1	0/376 (0%)	0
Cardiovascular insufficiency	0/386 (0%)	0	1/376 (0.3%)	1
Coronary artery disease	2/386 (0.5%)	2	0/376 (0%)	0
Left ventricular failure	1/386 (0.3%)	1	0/376 (0%)	0
Myocardial infarction	0/386 (0%)	0	1/376 (0.3%)	1
Myocardial ischaemia	0/386 (0%)	0	1/376 (0.3%)	1
Myocarditis	3/386 (0.8%)	3	0/376 (0%)	0
Sinus bradycardia	1/386 (0.3%)	1	0/376 (0%)	0
Ventricular fibrillation	1/386 (0.3%)	1	1/376 (0.3%)	1
Ear and labyrinth disorders
Deafness unilateral	0/386 (0%)	0	1/376 (0.3%)	1
Endocrine disorders
Adrenal insufficiency	3/386 (0.8%)	3	0/376 (0%)	0
Hypothyroidism	2/386 (0.5%)	2	0/376 (0%)	0
Eye disorders
Uveitis	1/386 (0.3%)	1	0/376 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/386 (0.3%)	1	0/376 (0%)	0
Abdominal pain upper	0/386 (0%)	0	1/376 (0.3%)	1
Colitis	1/386 (0.3%)	1	0/376 (0%)	0
Constipation	1/386 (0.3%)	1	0/376 (0%)	0
Diarrhoea	2/386 (0.5%)	2	0/376 (0%)	0
Diverticular perforation	1/386 (0.3%)	1	0/376 (0%)	0
Enteritis	0/386 (0%)	0	1/376 (0.3%)	1
Gastroduodenal ulcer	0/386 (0%)	0	1/376 (0.3%)	1
Gastrointestinal haemorrhage	2/386 (0.5%)	2	0/376 (0%)	0
Intestinal obstruction	1/386 (0.3%)	1	0/376 (0%)	0
Nausea	1/386 (0.3%)	1	2/376 (0.5%)	2
Small intestinal obstruction	1/386 (0.3%)	1	0/376 (0%)	0
Subileus	1/386 (0.3%)	1	0/376 (0%)	0
Upper gastrointestinal haemorrhage	0/386 (0%)	0	2/376 (0.5%)	2
Vomiting	1/386 (0.3%)	1	1/376 (0.3%)	1
General disorders
Asthenia	5/386 (1.3%)	5	2/376 (0.5%)	2
Chest pain	3/386 (0.8%)	3	1/376 (0.3%)	1
Complication of device insertion	1/386 (0.3%)	1	0/376 (0%)	0
Death	0/386 (0%)	0	1/376 (0.3%)	1
Fatigue	3/386 (0.8%)	3	3/376 (0.8%)	4
General physical health deterioration	1/386 (0.3%)	1	1/376 (0.3%)	1
Ill-defined disorder	0/386 (0%)	0	1/376 (0.3%)	1
Influenza like illness	1/386 (0.3%)	1	0/376 (0%)	0
Malaise	1/386 (0.3%)	1	1/376 (0.3%)	1
Multiple organ dysfunction syndrome	1/386 (0.3%)	1	0/376 (0%)	0
Necrosis	0/386 (0%)	0	1/376 (0.3%)	1
Non-cardiac chest pain	2/386 (0.5%)	3	0/376 (0%)	0
Oedema	1/386 (0.3%)	1	0/376 (0%)	0
Pain	1/386 (0.3%)	1	0/376 (0%)	0
Pyrexia	6/386 (1.6%)	7	2/376 (0.5%)	7
Hepatobiliary disorders
Hepatitis	1/386 (0.3%)	1	0/376 (0%)	0
Immune system disorders
Anaphylactic reaction	1/386 (0.3%)	1	0/376 (0%)	0
Hypersensitivity	1/386 (0.3%)	1	0/376 (0%)	0
Infections and infestations
Bacteraemia	1/386 (0.3%)	1	0/376 (0%)	0
Cellulitis	1/386 (0.3%)	1	0/376 (0%)	0
Clostridium difficile colitis	1/386 (0.3%)	1	0/376 (0%)	0
Encephalitis	1/386 (0.3%)	1	0/376 (0%)	0
Infected cyst	0/386 (0%)	0	1/376 (0.3%)	1
Infection	1/386 (0.3%)	1	1/376 (0.3%)	1
Influenza	0/386 (0%)	0	1/376 (0.3%)	1
Neutropenic sepsis	1/386 (0.3%)	1	0/376 (0%)	0
Nosocomial infection	1/386 (0.3%)	1	0/376 (0%)	0
Pneumonia	10/386 (2.6%)	10	10/376 (2.7%)	13
Pneumonia legionella	0/386 (0%)	0	1/376 (0.3%)	1
Pyelonephritis	1/386 (0.3%)	1	0/376 (0%)	0
Pyelonephritis acute	1/386 (0.3%)	3	0/376 (0%)	0
Sepsis	4/386 (1%)	4	4/376 (1.1%)	4
Septic shock	1/386 (0.3%)	1	0/376 (0%)	0
Spinal cord infection	1/386 (0.3%)	1	0/376 (0%)	0
Superinfection	1/386 (0.3%)	1	0/376 (0%)	0
Urinary tract infection	4/386 (1%)	5	1/376 (0.3%)	1
Urosepsis	2/386 (0.5%)	2	1/376 (0.3%)	1
Injury, poisoning and procedural complications
Facial bones fracture	0/386 (0%)	0	1/376 (0.3%)	1
Fall	3/386 (0.8%)	3	1/376 (0.3%)	1
Femur fracture	1/386 (0.3%)	1	1/376 (0.3%)	1
Infusion related reaction	2/386 (0.5%)	2	0/376 (0%)	0
Jaw fracture	1/386 (0.3%)	1	0/376 (0%)	0
Lower limb fracture	0/386 (0%)	0	1/376 (0.3%)	1
Multiple injuries	1/386 (0.3%)	1	0/376 (0%)	0
Road traffic accident	0/386 (0%)	0	1/376 (0.3%)	1
Subdural haematoma	1/386 (0.3%)	1	0/376 (0%)	0
Investigations
Alanine aminotransferase increased	1/386 (0.3%)	1	0/376 (0%)	0
Aspartate aminotransferase increased	1/386 (0.3%)	1	0/376 (0%)	0
Blood bilirubin increased	2/386 (0.5%)	2	0/376 (0%)	0
Blood creatine phosphokinase increased	1/386 (0.3%)	1	0/376 (0%)	0
Lymphocyte count decreased	1/386 (0.3%)	1	0/376 (0%)	0
Platelet count decreased	3/386 (0.8%)	3	1/376 (0.3%)	1
Transaminases increased	2/386 (0.5%)	2	0/376 (0%)	0
Troponin increased	1/386 (0.3%)	1	0/376 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	3/386 (0.8%)	3	2/376 (0.5%)	2
Failure to thrive	0/386 (0%)	0	1/376 (0.3%)	1
Hypercalcaemia	1/386 (0.3%)	1	0/376 (0%)	0
Hypocalcaemia	1/386 (0.3%)	1	0/376 (0%)	0
Hypokalaemia	1/386 (0.3%)	1	0/376 (0%)	0
Hyponatraemia	0/386 (0%)	0	1/376 (0.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	4/386 (1%)	4	2/376 (0.5%)	2
Back pain	3/386 (0.8%)	3	5/376 (1.3%)	5
Bone pain	6/386 (1.6%)	7	2/376 (0.5%)	2
Haemarthrosis	0/386 (0%)	0	1/376 (0.3%)	1
Muscle spasms	1/386 (0.3%)	1	0/376 (0%)	0
Muscular weakness	2/386 (0.5%)	3	0/376 (0%)	0
Musculoskeletal chest pain	0/386 (0%)	0	1/376 (0.3%)	1
Myalgia	1/386 (0.3%)	1	0/376 (0%)	0
Myositis	3/386 (0.8%)	3	0/376 (0%)	0
Neck pain	1/386 (0.3%)	1	1/376 (0.3%)	1
Pain in extremity	1/386 (0.3%)	1	0/376 (0%)	0
Pathological fracture	1/386 (0.3%)	1	0/376 (0%)	0
Torticollis	1/386 (0.3%)	1	0/376 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	0/386 (0%)	0	1/376 (0.3%)	2
Colon cancer	1/386 (0.3%)	1	1/376 (0.3%)	1
Renal cancer	0/386 (0%)	0	1/376 (0.3%)	1
Tumour pain	2/386 (0.5%)	2	1/376 (0.3%)	1
Tumour rupture	1/386 (0.3%)	1	0/376 (0%)	0
Nervous system disorders
Cerebral infarction	2/386 (0.5%)	2	0/376 (0%)	0
Cerebrovascular accident	3/386 (0.8%)	3	1/376 (0.3%)	1
Cranial nerve palsies multiple	1/386 (0.3%)	1	0/376 (0%)	0
Encephalopathy	1/386 (0.3%)	1	0/376 (0%)	0
Headache	0/386 (0%)	0	2/376 (0.5%)	2
Hypoaesthesia	1/386 (0.3%)	1	0/376 (0%)	0
IIIrd nerve paralysis	1/386 (0.3%)	1	0/376 (0%)	0
Ischaemic stroke	0/386 (0%)	0	1/376 (0.3%)	1
Lacunar infarction	0/386 (0%)	0	1/376 (0.3%)	1
Lethargy	1/386 (0.3%)	1	0/376 (0%)	0
Myasthenic syndrome	1/386 (0.3%)	1	0/376 (0%)	0
Neuropathy peripheral	1/386 (0.3%)	1	0/376 (0%)	0
Paraesthesia	1/386 (0.3%)	1	0/376 (0%)	0
Paralysis	1/386 (0.3%)	1	0/376 (0%)	0
Paraparesis	1/386 (0.3%)	1	1/376 (0.3%)	1
Peripheral motor neuropathy	1/386 (0.3%)	1	0/376 (0%)	0
Seizure	1/386 (0.3%)	1	0/376 (0%)	0
Spinal cord compression	1/386 (0.3%)	1	1/376 (0.3%)	1
Subarachnoid haemorrhage	1/386 (0.3%)	1	0/376 (0%)	0
Syncope	1/386 (0.3%)	1	0/376 (0%)	0
Transient ischaemic attack	0/386 (0%)	0	1/376 (0.3%)	1
Psychiatric disorders
Anxiety	1/386 (0.3%)	1	0/376 (0%)	0
Confusional state	0/386 (0%)	0	1/376 (0.3%)	1
Delirium	1/386 (0.3%)	1	0/376 (0%)	0
Renal and urinary disorders
Acute kidney injury	5/386 (1.3%)	5	1/376 (0.3%)	1
Haematuria	7/386 (1.8%)	13	5/376 (1.3%)	7
Hydronephrosis	1/386 (0.3%)	1	0/376 (0%)	0
Renal failure	1/386 (0.3%)	1	1/376 (0.3%)	1
Urinary retention	0/386 (0%)	0	1/376 (0.3%)	1
Urinary tract obstruction	0/386 (0%)	0	1/376 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/386 (0.3%)	1	2/376 (0.5%)	2
Hydrothorax	0/386 (0%)	0	1/376 (0.3%)	1
Hypercapnia	1/386 (0.3%)	1	0/376 (0%)	0
Pleural effusion	0/386 (0%)	0	1/376 (0.3%)	1
Pleuritic pain	0/386 (0%)	0	1/376 (0.3%)	1
Pneumonia aspiration	0/386 (0%)	0	1/376 (0.3%)	1
Pneumonitis	1/386 (0.3%)	1	0/376 (0%)	0
Pulmonary embolism	0/386 (0%)	0	1/376 (0.3%)	1
Respiratory arrest	0/386 (0%)	0	1/376 (0.3%)	1
Respiratory failure	1/386 (0.3%)	1	1/376 (0.3%)	1
Skin and subcutaneous tissue disorders
Erythema	2/386 (0.5%)	2	0/376 (0%)	0
Erythema multiforme	1/386 (0.3%)	1	0/376 (0%)	0
Rash	3/386 (0.8%)	3	0/376 (0%)	0
Rash maculo-papular	4/386 (1%)	4	0/376 (0%)	0
Stevens-Johnson syndrome	1/386 (0.3%)	1	0/376 (0%)	0
Surgical and medical procedures
Bladder neoplasm surgery	0/386 (0%)	0	1/376 (0.3%)	1
Vascular disorders
Haematoma	1/386 (0.3%)	1	0/376 (0%)	0
Hypertension	1/386 (0.3%)	1	1/376 (0.3%)	1
Hypertensive crisis	0/386 (0%)	0	1/376 (0.3%)	1
Hypotension	1/386 (0.3%)	1	1/376 (0.3%)	1
Pelvic venous thrombosis	1/386 (0.3%)	1	0/376 (0%)	0
Peripheral artery thrombosis	1/386 (0.3%)	1	0/376 (0%)	0
Other (Not Including Serious) Adverse Events
	Atezolizumab + Enzalutamide		Enzalutamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	348/386 (90.2%)		304/376 (80.9%)
Blood and lymphatic system disorders
Anaemia	82/386 (21.2%)	96	49/376 (13%)	58
Endocrine disorders
Hypothyroidism	23/386 (6%)	24	5/376 (1.3%)	5
Gastrointestinal disorders
Constipation	80/386 (20.7%)	90	61/376 (16.2%)	62
Diarrhoea	89/386 (23.1%)	111	41/376 (10.9%)	51
Nausea	93/386 (24.1%)	113	65/376 (17.3%)	72
Vomiting	35/386 (9.1%)	43	32/376 (8.5%)	35
General disorders
Asthenia	81/386 (21%)	97	62/376 (16.5%)	67
Fatigue	134/386 (34.7%)	152	102/376 (27.1%)	115
Oedema peripheral	34/386 (8.8%)	40	27/376 (7.2%)	30
Pain	23/386 (6%)	25	11/376 (2.9%)	11
Pyrexia	34/386 (8.8%)	41	9/376 (2.4%)	9
Infections and infestations
Nasopharyngitis	12/386 (3.1%)	14	20/376 (5.3%)	23
Urinary tract infection	21/386 (5.4%)	24	18/376 (4.8%)	21
Investigations
Weight decreased	54/386 (14%)	57	31/376 (8.2%)	32
Metabolism and nutrition disorders
Decreased appetite	117/386 (30.3%)	131	98/376 (26.1%)	113
Musculoskeletal and connective tissue disorders
Arthralgia	70/386 (18.1%)	86	46/376 (12.2%)	62
Back pain	82/386 (21.2%)	100	54/376 (14.4%)	62
Bone pain	27/386 (7%)	31	34/376 (9%)	38
Musculoskeletal chest pain	21/386 (5.4%)	25	14/376 (3.7%)	15
Musculoskeletal pain	30/386 (7.8%)	35	30/376 (8%)	35
Pain in extremity	26/386 (6.7%)	29	37/376 (9.8%)	43
Nervous system disorders
Dizziness	26/386 (6.7%)	31	20/376 (5.3%)	26
Headache	34/386 (8.8%)	37	19/376 (5.1%)	21
Psychiatric disorders
Insomnia	30/386 (7.8%)	30	28/376 (7.4%)	29
Respiratory, thoracic and mediastinal disorders
Cough	24/386 (6.2%)	25	16/376 (4.3%)	17
Dyspnoea	23/386 (6%)	25	17/376 (4.5%)	19
Skin and subcutaneous tissue disorders
Pruritus	36/386 (9.3%)	43	8/376 (2.1%)	8
Rash	54/386 (14%)	62	10/376 (2.7%)	10
Rash maculo-papular	21/386 (5.4%)	24	5/376 (1.3%)	6
Vascular disorders
Hot flush	14/386 (3.6%)	14	21/376 (5.6%)	22
Hypertension	27/386 (7%)	33	22/376 (5.9%)	22

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.