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

NCT03016312 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: CO393852016-003092-22
• Study Type: interventional
• Target: 759
• Locations: 20 countries
• Sites: 155

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.

Conditions

Prostatic Neoplasms, Castration-Resistant

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Percentage of Participants Who Survived at Month 6 and 12

  Months 6, 12

• Time to First Symptomatic Skeletal Event (SSE)

  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

  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

  Months 6, 12

• 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)

Study Arms (2)

Atezolizumab + Enzalutamide

EXPERIMENTAL

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; Drug: Enzalutamide

Enzalutamide

ACTIVE COMPARATOR

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

Interventions

Atezolizumab DRUG

Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg), intravenous (IV) infusion on Day 1 of each 21-day cycle.

Also known as: Tecentriq®

Atezolizumab + Enzalutamide

Enzalutamide DRUG

Enzalutamide capsules will be administered orally at a dose of 160 mg daily.

Also known as: Xtandi®

Atezolizumab + Enzalutamide; Enzalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (158)

City of Hope Medical Grp Inc.

Duarte, California, 91010, United States

Location

University of California San Diego

La Jolla, California, 92037-1337, United States

Location

Kaiser Permanente San Diego - Los Angeles

Los Angeles, California, 90027, United States

Location

UC Irvine Medical Center

Orange, California, 92868, United States

Location

Pacific Hematology Oncology Associates

San Francisco, California, 94115, United States

Location

University of Colorado; Division of Medical Oncology

Aurora, Colorado, 80021, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06510-3206, United States

Location

Stamford Hospital; BCC, MOHR

Stamford, Connecticut, 06904, United States

Location

Lynn Cancer Institute/Boca Raton Regional Hospital

Boca Raton, Florida, 33486, United States

Location

SCRI Florida Cancer Specialists South

Fort Myers, Florida, 33916, United States

Location

Miami Cancer Institute of Baptist Health, Inc.

Miami, Florida, 33176, United States

Location

Florida Cancer Specialist, North Region

St. Petersburg, Florida, 33705, United States

Location

Investigative Clin Rsch of IN

Indianapolis, Indiana, 46260, United States

Location

Associates in Oncology/Hematology P.C.

Rockville, Maryland, 20850, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute..

Detroit, Michigan, 48201, United States

Location

Nebraska Cancer Specialists; Oncology Hematology West, PC

Omaha, Nebraska, 68130, United States

Location

Urology Cancer Center & GU Research Network

Omaha, Nebraska, 68130, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89128, United States

Location

MSKCC at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

New York Oncology Hematology, P.C.

Albany, New York, 12208, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Oncology Hematology Care, Inc.

Cincinnati, Ohio, 45230, United States

Location

James Cancer Hospital;Solove Research Institute

Columbus, Ohio, 43210, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Allegheny Cancer Center

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh Cancer Institute; Division of Medical Oncology

Pittsburgh, Pennsylvania, 15232, United States

Location

Miriam Hospital

Providence, Rhode Island, 02906, United States

Location

Charleston Oncology, P .A

Charleston, South Carolina, 29414, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Sarah Cannon Research Institute / Tennessee Oncology

Chattanooga, Tennessee, 37404, United States

Location

Texas Oncology Cancer Center

Austin, Texas, 78731, United States

Location

Texas Oncology - Methodist Dallas Cancer Center

Dallas, Texas, 75203, United States

Location

Texas Oncology, P.A. - Fort Worth

Fort Worth, Texas, 76104, United States

Location

Texas Oncology - Memorial City

Houston, Texas, 77024, United States

Location

Texas Oncology-Tyler

Irving, Texas, 75063, United States

Location

Virginia Cancer Specialists - Alexandria

Alexandria, Virginia, 22304, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Eastern Health; Cancer Services

Box Hill, New South Wales, 3128, Australia

Location

Concord Repatriation General Hospital; Concord Cancer Centre

Concord, New South Wales, 2139, Australia

Location

Macquarie University Hospital

Macquarie Park, New South Wales, 2113, Australia

Location

Royal Brisbane & Women's Hosp; Cancer Care Serv

Herston, Queensland, 4029, Australia

Location

Adelaide Cancer Centre

Kurralta Park, South Australia, 5037, Australia

Location

Monash Medical Centre; Oncology

Clayton, Victoria, 3168, Australia

Location

LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie

Graz, 8036, Austria

Location

Ordensklinikum Linz Elisabethinen; Abteilung für Urologie und Andrologie

Linz, 4020, Austria

Location

Medizinische Universität Wien; Universitätsklinik für Urologie

Vienna, 1090, Austria

Location

Onze Lieve Vrouwziekenhuis Aalst

Aalst, 9300, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

CHU Sart-Tilman

Liège, 4000, Belgium

Location

Tom Baker Cancer Centre-Calgary

Calgary, Alberta, T2N 4N2, Canada

Location

Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

Lakeridge Health Oshawa; Oncology

Oshawa, Ontario, L1G 2B9, Canada

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 1Z5, Canada

Location

Hopital Charles Lemoyne; Centre Integre de Lutte Contre Le Cancer de La Monteregie

Greenfield Park, Quebec, J4V 2H1, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke - Hopital Fleurimont

Sherbrooke, Quebec, J1H 5N4, Canada

Location

CHU de Québec - Université Laval - Hôtel-Dieu de Québec

Québec, G1J 1Z4, Canada

Location

Friendship Hospital, Capital Medical University

Beijing, 100050, China

Location

Jiangsu Cancer Hospital

Nanjing, 211100, China

Location

Zhongshan Hospital Fudan University

Shanghai, 200032, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200120, China

Location

Masarykuv onkologicky ustav

Brno, 656 53, Czechia

Location

Fakultni nemocnice u sv. Anny v Brne

Brno, 656 91, Czechia

Location

Thomayerova nemocnice

Praha 4 - Krc, 140 59, Czechia

Location

Aalborg Universitetshospital; Onkologisk Afdeling

Aalborg, 9000, Denmark

Location

Herlev Hospital; Afdeling for Kræftbehandling

Herlev, 2730, Denmark

Location

Odense Universitetshospital, Onkologisk Afdeling R

Odense C, 5000, Denmark

Location

Institut Sainte-Catherine; Oncologie

Avignon, 84082, France

Location

Centre Francois Baclesse; Oncologie

Caen, 14076, France

Location

Hopital Louis Pasteur; Medecine B

Colmar, 68024, France

Location

Centre Oscar Lambret; Chir Cancerologie General

Lille, 59000, France

Location

Clinique Chenieux; Oncology

Limoges, 87039, France

Location

Hopital Saint Louis, Service D Oncologie Medicale

Paris, 75475, France

Location

Hopital d'Instruction des Armees de Begin

Saint-Mandé, 94160, France

Location

Institut Claudius Regaud; Departement Oncologie Medicale

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Universitätsklinikum Freiburg; Chirurgische Klinik; Abteilung Urologie

Freiburg im Breisgau, 79106, Germany

Location

Medizinische Hochschule Hannover; Klinik für Urologie und Onkologische Urologie

Hanover, 30625, Germany

Location

Universitätsklinikum Münster, Klinik für Urologie und Kinderurologie

Münster, 48149, Germany

Location

Universitätsklinikum Tübingen; Klinik für Urologie

Tübingen, 72076, Germany

Location

Urologisches Zentrum Euregio; Würselen, Urologische Praxis am Wasserturm

Würselen, 52146, Germany

Location

Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine

Athens, 115 22, Greece

Location

Alexandras Hospital; Dept. of Clin. Therapeutics, Athens Uni School of Medicine

Athens, 115 28, Greece

Location

Athens Medical Center; Dept. of Oncology

Athens, 151 25, Greece

Location

IASO General Hospital of Athens

Athens, 155 62, Greece

Location

Agioi Anargyroi Cancer Hospital; 2Nd Oncology Dept.

Kifissia, 145 64, Greece

Location

University Hospital of Patras Medical Oncology

Pátrai, 265 04, Greece

Location

Papageorgiou General Hospital; Medical Oncology

Thessaloniki, 564 29, Greece

Location

Semmelwies University of Medicine; Urology Dept.

Budapest, 1082, Hungary

Location

Orszagos Onkologiai Intezet; "C" Belgyógyászati-Onkológiai és Klinikai Farmakológiai Osztály

Budapest, 1122, Hungary

Location

Debreceni Egyetem Klinikai Kozpont ; Department of Oncology

Debrecen, 4032, Hungary

Location

Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica

Bari, Apulia, 70124, Italy

Location

IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia

San Giovanni Rotondo, Apulia, 71013, Italy

Location

ISTITUTO NAZIONALE TUMORI IRCCS FONDAZIONE G. PASCALE; Dipartimento Uro-Ginecologico

Napoli, Campania, 80131, Italy

Location

A.O. Universitaria Policlinico Di Modena; Oncologia

Modena, Emilia-Romagna, 41124, Italy

Location

Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica

Rome, Lazio, 00152, Italy

Location

IRCCS AOU San Martino - IST; Oncologia Medica 1

Genoa, Liguria, 16132, Italy

Location

A.O. Istituti Ospitalieri - Cremona; S.C. Oncologia

Cremona, Lombardy, 26100, Italy

Location

Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2

Milan, Lombardy, 20133, Italy

Location

Irccs Istituto Europeo Di Oncologia (IEO); Cure Mediche

Milan, Lombardy, 20141, Italy

Location

Ospedale Area Aretina Nord; U.O.C. Oncologia

Arezzo, Tuscany, 52100, Italy

Location

IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima

Padua, Veneto, 35128, Italy

Location

Nagoya City University Hospital

Aichi, 467-8602, Japan

Location

National Cancer Center East

Chiba, 277-8577, Japan

Location

Toho University Sakura Medical Center

Chiba, 285-8741, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

National Hospital Organization Hokkaido Cancer Center

Hokkaido, 003-0804, Japan

Location

Yokohama City University Medical Center

Kanagawa, 232-0024, Japan

Location

Kitasato University Hospital

Kanagawa, 252-0375, Japan

Location

University Hospital Kyoto Prefectural University of Medicine

Kyoto, 602-8566, Japan

Location

Nara Medical University Hospital

Nara, 634-8522, Japan

Location

Niigata University Medical & Dental Hospital

Niigata, 951-8520, Japan

Location

Kansai Medical University Hospital

Osaka, 573-1191, Japan

Location

Toranomon Hospital

Tokyo, 105-8470, Japan

Location

The Jikei University Hospital

Tokyo, 105-8471, Japan

Location

Nippon Medical School Hospital

Tokyo, 113-8603, Japan

Location

Woj. Wielospec. Centrum Onkologii i Traumatologii

?ód?, 93-513, Poland

Location

Medical University of Bialystok; Oncology clinic

Bialystok, 15-027, Poland

Location

Przychodnia Lekarska KOMED, Roman Karaszewski

Konin, 62-500, Poland

Location

Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii

Krakow, 30-688, Poland

Location

SPZOZ Opolskie Centrum Onkologii im. Prof. Tadeusza Koszarawskiego

Opole, 45-061, Poland

Location

Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina, Klinika Onkologii

Otwock, 05-400, Poland

Location

Szpital Sw. Elzbiety - Mokotowskie Centrum Medyczne Sp. z o.o.

Warsaw, 02-616, Poland

Location

Wojewodzki Szpital; Specjalistyczny ul.

Wroclaw, 51-124, Poland

Location

Russian Scientific Center of Roentgenoradiology

Moscow, Moscow Oblast, 117997, Russia

Location

P.A. Herzen Oncological Inst. ; Oncology

Moscow, Moscow Oblast, 125248, Russia

Location

SBEI HPE "The First St.Petersburg State Medical University n.a. acad. I.P.Pavlova"of MoH of RF

Saint Petersburg, Sankt-Peterburg, 197022, Russia

Location

National Cancer Center

Goyang-si, 10408, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Institut Catala d?Oncologia Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Insititut Catala D'Oncologia

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Corporacio Sanitaria Parc Tauli; Servicio de Oncologia

Sabadell, Barcelona, 8208, Spain

Location

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, Cordoba, 14004, Spain

Location

Clinica Universitaria de Navarra; Servicio de Oncologia

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitari Vall d'Hebron; Oncology

Barcelona, 08035, Spain

Location

Hospital Clínic i Provincial; Servicio de Oncología

Barcelona, 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia

Barcelona, 08041, Spain

Location

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, 28034, Spain

Location

Hospital Clinico San Carlos; Servicio de Oncologia

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, 28041, Spain

Location

Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia

Málaga, 29010, Spain

Location

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

Seville, 41013, Spain

Location

Inselspital Bern; Universitätsklinik für Medizinische Onkologie, Klinische Forschungseinheit

Bern, 3010, Switzerland

Location

Kantonsspital St. Gallen; Onkologie/Hämatologie

Sankt Gallen, 9007, Switzerland

Location

Taichung Veterans General Hospital; Division of Urology

Taichung, 407, Taiwan

Location

National Taiwan University Hospital, Department of Urology

Taipei, 10048, Taiwan

Location

TAIPEI VETERANS GENERAL HOSPITAL, Urology

Taipei, 11217, Taiwan

Location

Chang Gung Memorial Hospital-LinKou; Urology

Taoyuan District, 333, Taiwan

Location

Royal Blackburn Hospital

Blackburn, BB2 3HH, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

Barts and the London NHS Trust.

London, EC1A 7BE, United Kingdom

Location

Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Royal Marsden Hospital; Institute of Cancer Research

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35013615 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant

Interventions

atezolizumab; enzalutamide

Condition Hierarchy (Ancestors)

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2017
• First Posted: January 10, 2017
• Study Start: January 10, 2017
• Primary Completion: June 24, 2019
• Study Completion: December 20, 2022
• Last Updated: August 9, 2024
• Results First Posted: April 30, 2021

Record last verified: 2024-08

Locations

BE (3); CH (2); DK (3); DE (5); US (39); KR (4); AU (6); CZ (3); GR (7); CA (8); JP (14); IT (11); TW (4); HU (3); FR (9); ES (13); RU (3); PL (8); CN (4); GB (6)