The purpose of this study is to compare event-free survival (EFS) in participants with Bacillus Calmette-Guerin (BCG)-naive high-risk non-muscle invasive bladder cancer (HR-NMIBC), including high-grade papillary Ta, any T1, or carcinoma in situ (CIS), between TAR-200 plus cetrelimab (Group A) and TAR-200 alone (Group C) versus intravesical BCG (Group B).

A Study of TAR-200 in Combination With Cetrelimab or TAR-200 Alone Versus Intravesical Bacillus Calmette-Guérin (BCG) in Participants With BCG-naïve High-risk Non-muscle Invasive Bladder Cancer (HR-NMIBC)

Bladder Cancer

Urinary Bladder Neoplasms

Genitourinary Cancer

Advanced Solid Tumors

Prostate Neoplasms

Cancer

Advanced Solid Malignancies

Advanced Solid Tumor

Solid Tumor, Adult

Neoplasms

Adenocarcinoma

Advanced Stage Solid Tumors

Bladder cancer is the tenth most common malignancy worldwide. About 75 percent (%) of bladder cancers are non-muscle invasive at diagnosis with approximately 25% of NMIBC patients have HR, NMIBC. The TAR-200/gemcitabine (JNJ-17000139) product is an intravesical drug delivery system regulated as an investigational drug. The drug constituent consists of gemcitabine and osmotic minitablets. Cetrelimab (JNJ-63723283) is a fully human immunoglobulin G4 (IgG4) kappa monoclonal antibody (mAb) that binds programmed-cell death protein (PD)-1. The mainstay of treatment for HR-NMIBC is transurethral resection of bladder tumor, followed by intravesical treatment with BCG. In this study metronomic dosing of intravesical gemcitabine, delivered via TAR-200, alone or in combination with cetrelimab will be evaluated and compared against intravesical BCG. The study consists of a Screening phase, Treatment phase, and Follow-up phase. The total duration of the study will be up to 5 years and 2 months. Efficacy, Safety, pharmacokinetics (PK), and biomarkers will be assessed at specific time points during the study.

Cetrelimab

TAR-200

BCG Vesiculture

A Phase 3, Open-Label, Multi-Center, Randomized Study Evaluating the Efficacy and Safety of TAR-200 in Combination With Cetrelimab or TAR-200 Alone Versus Intravesical Bacillus Calmette-Guérin (BCG) in Participants With BCG-naïve High-Risk Non-Muscle Invasive Bladder Cancer

EFS is defined as the time from randomization to either the time of the first recurrence of high-risk disease, progression, or death due to any cause, whichever occurs first. For participants with carcinoma In-situ (CIS), persistent disease at 6 months (Week 24) is also considered an EFS event. Progression is defined as: an increase of stage from Ta to T1 or from CIS to T1 or progression to muscle invasive bladder cancer (MIBC) (T greater than or equal to [>=] 2) or to lymph node (N+) or to distant disease (M+), whichever occurs first.

Overall CR will be measured by determining the percentage of participants with CIS who have no presence of high-risk disease at 6 months.

Duration of CR is defined from the time of first CR achieved to first evidence of recurrence, progression or death due to any cause (whichever occurs first) for participants who achieve a CR.

RFS is defined as the time from randomization to the time of the first recurrence of high-risk disease, or death due to any cause, whichever occurs first.

TTP is defined as the time from randomization to the date of first documented evidence of disease progression or death due to disease progression, whichever occurs first.

OS is defined as the time from randomization to death, due to any cause.

CSS is defined as the time from randomization to the date of death due to bladder cancer.

Number of participants with AEs by severity grade as assessed by CTCAE version 5 will be reported. Grade refers to the severity of AE as follows: Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life-threatening; Grade 5- Death related to adverse event.

Number of participants with AEs will be reported. An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product.

Number of participants with change from baseline in laboratory abnormalities will be reported. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1- Mild, Grade 2- Moderate, Grade 3- Severe, Grade 4- Life-threatening, and Grade 5- Death related to adverse event.

Number of participants with change from baseline in vital signs (blood pressure [systolic and diastolic], heart rate, temperature, and weight) abnormalities will be reported.

EORTC QLQ-NMIBC 24 is a 24-item questionnaire for evaluating the Health-related quality of life (HRQoL) of participants with superficial (non-muscle-invasive) bladder cancer. The questionnaire is designed to supplement the quality of life questionnaire (QLQ-C30) and incorporates 6 multi-item scales and 5 single items. Ratings for each item range from 1 (not at all) to 4 (very much).

EORTC QLQ-NMIBC 24 is a 24-item questionnaire for evaluating the HRQoL of participants with superficial (non-muscle-invasive) bladder cancer. The questionnaire is designed to supplement the QLQ-C30 and incorporates 6 multi-item scales and 5 single items. Ratings for each item range from 1 (not at all) to 4 (very much).

Participants will receive intravesical TAR-200 once every 3 weeks (Q3W) and cetrelimab.

Participants will receive intravesical BCG once every week for 6 weeks (induction) and then followed by once every week for 3 weeks starting at Weeks 12, 24, 48, 72, and 96 (maintenance).

Participants will receive intravesical TAR-200 alone once Q3W.

The purpose of this study is to compare event-free survival (EFS) in participants with
      Bacillus Calmette-Guerin (BCG)-naive high-risk non-muscle invasive bladder cancer (HR-NMIBC),
      including high-grade papillary Ta, any T1, or carcinoma in situ (CIS), between TAR-200 plus
      cetrelimab (Group A) and TAR-200 alone (Group C) versus intravesical BCG (Group B).

A Study of TAR-200 in Combination With Cetrelimab or TAR-200 Alone Versus Intravesical Bacillus Calmette-Guérin (BCG) in Participants With BCG-naïve High-risk Non-muscle Invasive Bladder Cancer

Bladder cancer is the tenth most common malignancy worldwide. About 75 percent (%) of bladder
      cancers are non-muscle invasive at diagnosis with approximately 25% of NMIBC patients have
      HR, NMIBC. The TAR-200/gemcitabine (JNJ-17000139) product is an intravesical drug delivery
      system regulated as an investigational drug. The drug constituent consists of gemcitabine and
      osmotic minitablets. Cetrelimab (JNJ-63723283) is a fully human immunoglobulin G4 (IgG4)
      kappa monoclonal antibody (mAb) that binds programmed-cell death protein (PD)-1. The mainstay
      of treatment for HR-NMIBC is transurethral resection of bladder tumor, followed by
      intravesical treatment with BCG. In this study metronomic dosing of intravesical gemcitabine,
      delivered via TAR-200, alone or in combination with cetrelimab will be evaluated and compared
      against intravesical BCG. The study consists of a Screening phase, Treatment phase, and
      Follow-up phase. The total duration of the study will be up to 5 years and 2 months.
      Efficacy, Safety, pharmacokinetics (PK), and biomarkers will be assessed at specific time
      points during the study.

Arkansas Urology

Genesis Research, LLC - West Coast Urology

Genesis Research

Providence Medical Foundation

Colorado Clinical Research

Urological Research Network

Blessing Hospital

Urology of Indiana

First Urology

AMR Kansas City Oncology

Wichita Urology Group

Chesapeake Urology Research Associates

The Urology Center, PC

Associated Medical Professionals of Ny

SUNY Upstate Med Univ

Vidant Urology - Greenville

Centers for Advanced Urology, LLC; d/b/a MidLantic Urology

Carolina Urologic Research Center

Urology Associates

Houston Metro Urology

Urology San Antonio Research

George E. Wahlen VAMC

Urology Of Virginia, Pllc

Spokane Urology

Hospital Italiano de Buenos Aires

Sociedade Beneficente de Senhoras - Hospital Sírio Libanês

Centro Urologico Profesor Bengio

Hospital Privado - Centro Medico de Cordoba

Cemaic - Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica

Hospital Privado de la Comunidad

Instituto Médico Río Cuarto

Austin Health

Macquarie University Hospital

Hollywood Private Hospital

Mater Hospital Brisbane

ZNA Middelheim

AZ Sint-Jan

AZ Maria Middelares

UZ Gent

Centre Hospitalier de l'Ardenne

AZ Delta

Vitaz

GZA Ziekenhuizen- Campus St Augustinus

Fundacao Pio XII

NAIC - Nair Antunes Instituto do Câncer

Universidade Estadual De Campinas

Liga Paranaense de Combate ao Cancer

Hospital Regional do Câncer - Hospital de Esperança

Hospital Ana Nery Santa Cruz do Sul

Real e Benemérita Associação Portuguesa de Beneficência

Fundacao Antonio Prudente - A.C. Camargo Cancer Center

Nova Scotia Health Authority

St Josephs Healthcare Hamilton

Princess Margaret Cancer Centre University Health Network

CHUM - Centre hospitalier universitaire de Montreal

CHU de Quebec-Universite Laval-Hopital de l'Enfant-Jesus

Peking University First Hospital

Beijing Luhe Hospital, Capital Medical University

The First Bethune Hospital of Jilin University

West China Hospital Sichuan University

Chongqing University Cancer Hospital

People's Hospital of Deyang City

Sun Yat-Sen University Cancer Center

Zhejiang Provincial People's Hospital

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Nanjing Drum Tower Hospital

The First Affiliated Hospital of Ningbo University

Ruijing Hospital Affiliated To Shanghai Jiaotong University School Of Medicine

Huadong Hospital Affiliated to Fudan University

Shengjing Hospital of China Medical University

The Second Hospital of Tianjin Medical University

The First Affiliated Hospital of Wenzhou Medical University

TongJi Hospital of TongJi Medical College of Huazhong University of Science & Technology

First Affiliated Hospital of Medical College of Xi'an Jiaotong University

Yantai Yuhuangding Hospital

Fakultni nemocnice u sv. Anny v Brne

Fakultni nemocnice Hradec Kralove

Krajská nemocnice Liberec a.s.

Fakultní nemocnice Olomouc

Fakultni nemocnice v Motole

Thomayerova nemocnice, Onkologicka klinika

Fakultni nemocnice Kralovske Vinohrady

Polyclinique Bordeaux Nord Acquitaine

CHU Gabriel-Montpied

CHU Grenoble

Polyclinique de Limoges - Francois Chenieux

Hôpital Edouard Herriot

CHU de Nantes hotel-Dieu

CHU Nîmes

Centre Hospitalier Regional d'Orleans (CHRO) - Hopital La Source

Groupe Hospitalier Diaconesses Croix Saint Simon

Hopital Europeen Georges-Pompidou

APHP - Hopital Bichat - Claude Bernard

Clinical La Croix Du Sud - Ramsay Santé

Chu Rennes - Hopital Pontchaillou

CHU Rangueil

Urologicum Duisburg

Universitätsklinikum Erlangen

Universitatsklinikum Essen

Universitaetsklinikum Frankfurt

Eme Red Hospitalaria

VA NY Harbor Healthcare System

Sir Run Run Shaw Hospital Zhejiang University School of Medicine

Universitaetsklinikum Freiburg

Klinikum Nurnberg Nord

Medizinisches Versorgungszentrum - Urologie

Universitat Tubingen

Tata Memorial Hospital

Oncologico Potosino

Canisius-Wilhelmina Ziekenhuis

Radboud Umcn

Chungbuk National University Hospital

Kyungpook National University Chilgok Hospital

National Cancer Center

Chonnam National University Hwasun Hospital

Korea University Anam Hospital

Seoul National University Hospital

Kangbuk Samsung Hospital

Severance Hospital Yonsei University Health System

Hosp Univ A Coruna

Clinica Univ. de Navarra

Hosp. Univ. 12 de Octubre

Hosp. Univ. La Paz

Mayo Clinic

Orlando Health Cancer Institute

Duly Health and Care

Liga Norte Riograndense Contra O Cancer

Cedars Sinai Medical Center

UC Davis Comprehensive Cancer Center

VA Long Beach Health Care System

Providence Saint Johns Cancer Institute

Sarasota Memorial Hospital

Grady Memorial Hospital

The Emory Clinic Department of Urology

Northwestern University

Lahey Hospital & Medical Center

University of Michigan

University Of Minnesota

Mayo Clinic Rochester

Cooper Health System MD Anderson Cancer Center at Cooper

Icahn School of Medicine at Mt. Sinai

Cleveland Clinic

Central Ohio Urology Group

Centers for Advanced Urology LLC d b a MidLantic Urology

Thomas Jefferson University Hospital

UPMC Shadyside Hospital

Vanderbilt University Medical Center

Urology Austin

Urology Clinics of North Texas

Houston Methodist Hospital

Huntsman Cancer Institute

Sociedade Beneficente de Senhoras Hospital Sirio Libanes

Cemaic Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica

Hospital Privado Centro Medico de Cordoba

Instituto Medico Rio Cuarto

AZ Sint-Lucas

A Study of TAR-200 in Combination With Cetrelimab or TAR-200 Alone Versus Intravesical Bacillus Calmette-Guérin (BCG) in Participants With BCG-naïve High-risk Non-muscle Invasive Bladder Cancer (HR-NMIBC)

Trials at a glance

Trials at a glance

A Study of TAR-200 in Combination With Cetrelimab or TAR-200 Alone Versus Intravesical Bacillus Calmette-Guérin (BCG) in Participants With BCG-naïve High-risk Non-muscle Invasive Bladder Cancer (HR-NMIBC)

Outcome measures

Primary outcome measures

Secondary outcome measures