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 (IMbassador250)

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

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.

Study Overview

• Status: Completed
• Conditions: Prostatic Neoplasms, Castration-Resistant
• Intervention / Treatment: Drug: Atezolizumab; Drug: Enzalutamide

• Study Type: Interventional
• Enrollment (Actual): 759
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Box Hill, New South Wales, Australia, 3128
      • Eastern Health; Cancer Services
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital; Concord Cancer Centre
    • Macquarie Park, New South Wales, Australia, 2113
      • Macquarie University Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane & Women's Hosp; Cancer Care Serv
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
      • Adelaide Cancer Centre
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre; Oncology
• Austria
  • Graz, Austria, 8036
    • LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie
  • Linz, Austria, 4020
    • Ordensklinikum Linz Elisabethinen; Abteilung für Urologie und Andrologie
  • Wien, Austria, 1090
    • Medizinische Universität Wien; Universitätsklinik für Urologie
• Belgium
  • Aalst, Belgium, 9300
    • Onze Lieve Vrouwziekenhuis Aalst
  • Gent, Belgium, 9000
    • Uz Gent
  • Liège, Belgium, 4000
    • CHU Sart-Tilman
• Canada
  • Quebec, Canada, G1J 1Z4
    • CHU de Québec - Université Laval - Hôtel-Dieu de Québec
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre-Calgary
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston General Hospital
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health Oshawa; Oncology
    • Toronto, Ontario, Canada, M5G 1Z5
      • Princess Margaret Cancer Center
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Hopital Charles Lemoyne; Centre Integre de Lutte Contre Le Cancer de La Monteregie
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke - Hopital Fleurimont
• China
  • Beijing, China, 100050
    • Friendship Hospital, Capital Medical University
  • Nanjing City, China, 211100
    • Jiangsu Cancer Hospital
  • Shanghai, China, 200032
    • Zhongshan Hospital Fudan University
  • Shanghai City, China, 200120
    • Fudan University Shanghai Cancer Center
• Czechia
  • Brno, Czechia, 656 53
    • Masarykuv Onkologicky Ustav
  • Brno, Czechia, 656 91
    • Fakultni nemocnice u sv. Anny v Brne
  • Praha 4 - Krc, Czechia, 140 59
    • Thomayerova nemocnice
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Universitetshospital; Onkologisk Afdeling
  • Herlev, Denmark, 2730
    • Herlev Hospital; Afdeling for Kræftbehandling
  • Odense C, Denmark, 5000
    • Odense Universitetshospital, Onkologisk Afdeling R
• France
  • Avignon, France, 84082
    • Institut Sainte-Catherine; Oncologie
  • Caen, France, 14076
    • Centre Francois Baclesse; Oncologie
  • Colmar, France, 68024
    • Hopital Louis Pasteur; Medecine B
  • Lille, France, 59000
    • Centre Oscar Lambret; Chir Cancerologie General
  • Limoges, France, 87039
    • Clinique Chenieux; Oncology
  • Paris, France, 75475
    • Hopital Saint Louis, Service D Oncologie Medicale
  • Saint-Mande, France, 94160
    • Hopital d'Instruction des Armees de Begin
  • Toulouse, France, 31059
    • Institut Claudius Regaud; Departement Oncologie Medicale
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg; Chirurgische Klinik; Abteilung Urologie
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover; Klinik für Urologie und Onkologische Urologie
  • Münster, Germany, 48149
    • Universitatsklinikum Munster, Klinik fur Urologie und Kinderurologie
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen; Klinik für Urologie
  • Würselen, Germany, 52146
    • Urologisches Zentrum Euregio; Würselen, Urologische Praxis am Wasserturm
• Greece
  • Athens, Greece, 115 22
    • Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine
  • Athens, Greece, 155 62
    • IASO General Hospital of Athens
  • Athens, Greece, 115 28
    • Alexandras Hospital; Dept. of Clin. Therapeutics, Athens Uni School of Medicine
  • Athens, Greece, 151 25
    • Athens Medical Center; Dept. of Oncology
  • Kifisia, Greece, 145 64
    • Agioi Anargyroi Cancer Hospital; 2Nd Oncology Dept.
  • Patras, Greece, 265 04
    • University Hospital of Patras Medical Oncology
  • Thessaloniki, Greece, 564 29
    • Papageorgiou General Hospital; Medical Oncology
• Hungary
  • Budapest, Hungary, 1082
    • Semmelwies University of Medicine; Urology Dept.
  • Budapest, Hungary, 1122
    • Orszagos Onkologiai Intezet; "C" Belgyógyászati-Onkológiai és Klinikai Farmakológiai Osztály
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont ; Department of Oncology
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • ISTITUTO NAZIONALE TUMORI IRCCS FONDAZIONE G. PASCALE; Dipartimento Uro-Ginecologico
  • Emilia-Romagna
    • Modena, Emilia-Romagna, Italy, 41124
      • A.O. Universitaria Policlinico Di Modena; Oncologia
  • Lazio
    • Roma, Lazio, Italy, 00152
      • Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica
  • Liguria
    • Genova, Liguria, Italy, 16132
      • IRCCS AOU San Martino - IST; Oncologia Medica 1
  • Lombardia
    • Cremona, Lombardia, Italy, 26100
      • A.O. Istituti Ospitalieri - Cremona; S.C. Oncologia
    • Milano, Lombardia, Italy, 20133
      • Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
    • Milano, Lombardia, Italy, 20141
      • Irccs Istituto Europeo Di Oncologia (IEO); Cure Mediche
  • Puglia
    • Bari, Puglia, Italy, 70124
      • Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica
    • San Giovanni Rotondo, Puglia, Italy, 71013
      • IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia
  • Toscana
    • Arezzo, Toscana, Italy, 52100
      • Ospedale Area Aretina Nord; U.O.C. Oncologia
  • Veneto
    • Padova, Veneto, Italy, 35128
      • IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima
• Japan
  • Aichi, Japan, 467-8602
    • Nagoya City University Hospital
  • Chiba, Japan, 285-8741
    • Toho University Sakura Medical Center
  • Chiba, Japan, 277-8577
    • National Cancer Center East
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Hokkaido, Japan, 003-0804
    • National Hospital Organization Hokkaido Cancer Center
  • Kanagawa, Japan, 252-0375
    • Kitasato University Hospital
  • Kanagawa, Japan, 232-0024
    • Yokohama City University Medical Center
  • Kyoto, Japan, 602-8566
    • University Hospital Kyoto Prefectural University of Medicine
  • Nara, Japan, 634-8522
    • Nara Medical University Hospital
  • Niigata, Japan, 951-8520
    • Niigata University Medical & Dental Hospital
  • Osaka, Japan, 573-1191
    • Kansai Medical University Hospital
  • Tokyo, Japan, 105-8470
    • Toranomon Hospital
  • Tokyo, Japan, 105-8471
    • The Jikei University Hospital
  • Tokyo, Japan, 113-8603
    • Nippon Medical School Hospital
• Korea, Republic of
  • Goyang-si, Korea, Republic of, 10408
    • National Cancer Center
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Poland
  • ?ód?, Poland, 93-513
    • Woj. Wielospec. Centrum Onkologii i Traumatologii
  • Bialystok, Poland, 15-027
    • Medical University of Bialystok; Oncology clinic
  • Konin, Poland, 62-500
    • Przychodnia Lekarska KOMED, Roman Karaszewski
  • Kraków, Poland, 30-688
    • Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii
  • Opole, Poland, 45-061
    • SPZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarawskiego
  • Otwock, Poland, 05-400
    • Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii
  • Warszawa, Poland, 02-616
    • Szpital Sw. Elzbiety - Mokotowskie Centrum Medyczne Sp. z o.o.
  • Wroclaw, Poland, 51-124
    • Wojewodzki Szpital; Specjalistyczny ul.
• Russian Federation
  • Moskovskaja Oblast
    • Moscow, Moskovskaja Oblast, Russian Federation, 117997
      • Russian Scientific Center of Roentgenoradiology
    • Moscow, Moskovskaja Oblast, Russian Federation, 125248
      • P.A. Herzen Oncological Inst. ; Oncology
  • Sankt Petersburg
    • Sankt-peterburg, Sankt Petersburg, Russian Federation, 197022
      • SBEI HPE "The First St.Petersburg State Medical University n.a. acad. I.P.Pavlova"of MoH of RF
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron; Oncology
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial; Servicio de Oncología
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Oncologia
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos; Servicio de Oncologia
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre; Servicio de Oncologia
  • Malaga, Spain, 29010
    • Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio; Servicio de Oncologia
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Institut Catala d?Oncologia Hospital Germans Trias i Pujol
    • Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Insititut Catala D'Oncologia
    • Sabadell, Barcelona, Spain, 8208
      • Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
  • Cordoba
    • Córdoba, Cordoba, Spain, 14004
      • Hospital Universitario Reina Sofia; Servicio de Oncologia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra; Servicio de Oncologia
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital Bern; Universitätsklinik für Medizinische Onkologie, Klinische Forschungseinheit
  • St. Gallen, Switzerland, 9007
    • Kantonsspital St. Gallen; Onkologie/Hämatologie
• Taiwan
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital; Division of Urology
  • Taipei, Taiwan, 10048
    • National Taiwan University Hospital, Department of Urology
  • Taipei, Taiwan, 11217
    • TAIPEI VETERANS GENERAL HOSPITAL, Urology
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital-LinKou; Urology
• United Kingdom
  • Blackburn, United Kingdom, BB2 3HH
    • Royal Blackburn Hospital
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute
  • London, United Kingdom, EC1A 7BE
    • Barts and the London NHS Trust.
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital; Institute of Cancer Research
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Grp Inc.
    • La Jolla, California, United States, 92037-1337
      • University of California San Diego
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente San Diego - Los Angeles
    • Orange, California, United States, 92868
      • UC Irvine Medical Center
    • San Francisco, California, United States, 94115
      • Pacific Hematology Oncology Associates
  • Colorado
    • Aurora, Colorado, United States, 80021
      • University of Colorado; Division of Medical Oncology
  • Connecticut
    • New Haven, Connecticut, United States, 06510-3206
      • Yale School of Medicine
    • Stamford, Connecticut, United States, 06904
      • Stamford Hospital; BCC, MOHR
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Lynn Cancer Institute/Boca Raton Regional Hospital
    • Fort Myers, Florida, United States, 33916
      • SCRI Florida Cancer Specialists South
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute of Baptist Health, Inc.
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialist, North Region
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Investigative Clin Rsch of IN
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Associates in Oncology/Hematology P.C.
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute..
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Urology Cancer Center & GU Research Network
    • Omaha, Nebraska, United States, 68130
      • Nebraska Cancer Specialists; Oncology Hematology West, PC
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Comprehensive Cancer Centers of Nevada
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • MSKCC at Basking Ridge
  • New York
    • Albany, New York, United States, 12208
      • New York Oncology Hematology, P.C.
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45230
      • Oncology Hematology Care, Inc.
    • Columbus, Ohio, United States, 43210
      • James Cancer Hospital;Solove Research Institute
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute; Division of Medical Oncology
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Miriam Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Charleston Oncology, P .A
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Sarah Cannon Research Institute / Tennessee Oncology
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology Cancer Center
    • Dallas, Texas, United States, 75203
      • Texas Oncology - Methodist Dallas Cancer Center
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology, P.A. - Fort Worth
    • Houston, Texas, United States, 77024
      • Texas Oncology - Memorial City
    • Irving, Texas, United States, 75063
      • Texas Oncology-Tyler
  • Virginia
    • Alexandria, Virginia, United States, 22304
      • Virginia Cancer Specialists - Alexandria
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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®

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Symptomatic Skeletal Event (SSE)	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.	Baseline up to end of study (up to approximately 42 months)
Radiographic Progression-Free Survival (rPFS), as Assessed by the Investigator and Adapted From the PCWG3 Criteria	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	Baseline until disease progression or death from any cause (up to approximately 42 months)
Percentage of Participants Who Are Radiographic Progression-Free, as Assessed by the Investigator and Adapted From the PCWG3 Criteria	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	Months 6, 12
Percentage of Participants With Greater Than (>) 50 Percent (%) Decrease in Prostate-Specific Antigen (PSA) From Baseline	PSA response rate, defined as a > 50% decrease in PSA from baseline that is confirmed after ≥ 3 weeks by a consecutive confirmatory PSA measurement	Baseline until disease progression (up to approximately 42 months)
Time to PSA Progression, Assessed as Per PCWG3 Criteria	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.	Baseline until disease progression (up to approximately 42 months)
Percentage of Participant With Objective Response, as Determined by the Investigator Through Use of PCWG3 Criteria	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	Baseline until disease progression or death from any cause (up to approximately 42 months)
Percentage of Participants Who Survived at Month 6 and 12	OS (Overall Survival is defined as the time from randomization to death from any cause) probability at 6 and 12 months	Months 6, 12
Percentage of Participants With Adverse Events	Verbatim description of adverse events will be coded to MedDRA preferred terms and graded according to NCI CTCAE v4.0.	Baseline up to end of study (up to approximately 42 month)
Minimum Observed Serum Concentration (Cmin) of Atezolizumab	Safety visit-Discontinued participants had these visits within approximately 120 days after the last dosing; Study Completion Pre-dose visit-Participants had these visits at the last treatment dosing, samples were taken before the last dosing; Early Discontinuation Pre-dose visit-Participants who discontinued the study had these visits within the 30 days after their last dosing but samples were takes before their last dosing; Study Completion visit-Participants had these visits at their last treatment dosing but samples were taken after their last dosing; Early Discontinuation visit-Participants who discontinued the study had the visits within the 30 days after their last dosing but samples were taken after their last dosing; Unscheduled and Unscheduled Pre-dose Visits- At these visits, participants' samples were collected without dosing event and before dosing dosing at a visit unscheduled per protocol respectively. Enzalutamide Arm had no Atezolizumab dosing.	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)
Maximum Observed Serum Concentration (Cmax) of Atezolizumab	Safety visit-Discontinued participants had these visits within approximately 120 days after the last dosing; Study Completion Pre-dose visit-Participants had these visits at the last treatment dosing, samples were taken before the last dosing; Early Discontinuation Pre-dose visit-Participants who discontinued the study had these visits within the 30 days after their last dosing but samples were takes before their last dosing; Study Completion visit-Participants had these visits at their last treatment dosing but samples were taken after their last dosing; Early Discontinuation visit-Participants who discontinued the study had the visits within the 30 days after their last dosing but samples were taken after their last dosing; Unscheduled and Unscheduled Pre-dose Visits- At these visits, participants' samples were collected without dosing event and before dosing dosing at a visit unscheduled per protocol respectively. Enzalutamide Arm had no Atezolizumab dosing.	Day Cycle 1 Day 1 0.5 hr post-infusion (infusion duration: 60 minutes [min])
Plasma Concentration of Enzalutamide	Safety visit-Discontinued participants had these visits within approximately 120 days after the last dosing; Study Completion Pre-dose visit-Participants had these visits at the last treatment dosing, samples were taken before the last dosing; Early Discontinuation Pre-dose visit-Participants who discontinued the study had these visits within the 30 days after their last dosing but samples were takes before their last dosing; Study Completion visit-Participants had these visits at their last treatment dosing but samples were taken after their last dosing; Early Discontinuation visit-Participants who discontinued the study had the visits within the 30 days after their last dosing but samples were taken after their last dosing; Unscheduled and Unscheduled Pre-dose Visits- At these visits, participants' samples were collected without dosing event and before dosing dosing at a visit unscheduled per protocol respectively. Enzalutamide Arm had no Atezolizumab dosing.	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 Concentration of N-Desmethyl Enzalutamide	Safety visit-Discontinued participants had these visits within approximately 120 days after the last dosing; Study Completion Pre-dose visit-Participants had these visits at the last treatment dosing, samples were taken before the last dosing; Early Discontinuation Pre-dose visit-Participants who discontinued the study had these visits within the 30 days after their last dosing but samples were takes before their last dosing; Study Completion visit-Participants had these visits at their last treatment dosing but samples were taken after their last dosing; Early Discontinuation visit-Participants who discontinued the study had the visits within the 30 days after their last dosing but samples were taken after their last dosing; Unscheduled and Unscheduled Pre-dose Visits- At these visits, participants' samples were collected without dosing event and before dosing dosing at a visit unscheduled per protocol respectively. Enzalutamide Arm had no Atezolizumab dosing.	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
Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab	The numbers and proportions of ADA-positive participants and ADA-negative participants at baseline (baseline prevalence) and after baseline (post-baseline incidence) will be summarized by treatment group. Enzalutamide Arm has no Atezolizumab dosing therefore no participants to include here for Atezolizumab ADA.	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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Powles T, Yuen KC, Gillessen S, Kadel EE 3rd, Rathkopf D, Matsubara N, Drake CG, Fizazi K, Piulats JM, Wysocki PJ, Buchschacher GL Jr, Alekseev B, Mellado B, Karaszewska B, Doss JF, Rasuo G, Datye A, Mariathasan S, Williams P, Sweeney CJ. Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. Nat Med. 2022 Jan;28(1):144-153. doi: 10.1038/s41591-021-01600-6. Epub 2022 Jan 10.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2017
• Primary Completion (Actual): June 24, 2019
• Study Completion (Actual): December 20, 2022

Study Registration Dates

• First Submitted: January 9, 2017
• First Submitted That Met QC Criteria: January 9, 2017
• First Posted (Estimated): January 10, 2017

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 8, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Atezolizumab
• Other Study ID Numbers: CO39385; 2016-003092-22 (EudraCT Number)

Drug and device information, study documents

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