A Study of TAR-200 in Combination With Cetrelimab, TAR-200 Alone, or Cetrelimab Alone in Participants With Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Intravesical Bacillus Calmette-Guérin Who Are Ineligible for or Elected Not to Undergo Radical Cystectomy
- Conditions
- Urinary Bladder Neoplasms
- Interventions
- Registration Number
- NCT04640623
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to evaluate the overall complete response (CR) rate in participants treated with TAR-200 in combination with cetrelimab (Cohort 1), or TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3) with Carcinoma in Situ (CIS), with or without concomitant high-grade Ta or T1 papillary disease; and disease-free survival (DFS) in participants treated with TAR-200 alone with papillary disease only (Cohort 4).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 220
- Histologically confirmed diagnosis of persistent or recurrent high-risk non-muscle invasive bladder cancer (HR-NMIBC), (carcinoma in situ [CIS] or tumor in situ [Tis]), with or without papillary disease (T1, high-grade Ta) or papillary disease only (high-grade Ta or any T1 and absence of CIS), within 12 months of completion of the last dose of Bacillus Calmette-Guerin (BCG) therapy, in participants who have received adequate BCG. Mixed histology tumors are allowed if urothelial differentiation (transitional cell histology) is predominant. However, the presence of neuroendocrine, micropapillary, signet ring cell, plasmacytoid, or sarcomatoid features will make a participant ineligible. For participants with lamina propria invasion (T1) on the screening biopsy/ transurethral resection of bladder tumor (TURBT), muscularis propria must be present in order to rule out Muscle Invasive Bladder Cancer (MIBC)
- All visible papillary disease must be fully resected (absent) prior to randomization (residual CIS is acceptable for participants eligible for Cohorts 1, 2, and 3 only) and documented in the electronic case report form (eCRF) at screening cystoscopy. For participants with papillary disease only (Cohort 4), local urine cytology at screening must be negative or atypical (for High-Grade Urothelial Carcinoma [HGUC])
- Participants must be ineligible for or have elected not to undergo radical cystectomy
- BCG-unresponsive high-risk NMIBC after treatment with adequate BCG therapy defined as a minimum of 5 of 6 full doses of an induction course (adequate induction) plus 2 of 3 doses of a maintenance course, or at least 2 of 6 doses of a second induction course
- Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2
- Presence or history of histologically confirmed, muscle-invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (that is, T2, T3, T4, and/or Stage IV)
- Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder. Ta/T1/CIS of the upper urinary tract (including renal pelvis and ureter) is allowable if treated with complete nephroureterectomy more than 24 months prior to randomization
- Received a live virus vaccine within 30 days prior to the initiation of study treatment. Inactivated (non-live or non-replicating) vaccines approved or authorized for emergency use (for example, COVID-19) by local health authorities are allowed
- Active hepatitis B or C infection (for example, participants with history of hepatitis C infection but undetectable hepatitis C virus polymerase chain reaction (PCR) test and participants with history of hepatitis B infection with positive hepatitis B surface antigen (HBsAg) antibody and undetectable PCR are allowed)
- Prior therapy with an anti-programmed-cell death 1 (PD-1), anti-PD-ligand 2 (L2) agent, or with an agent directed to another co-inhibitory T-cell receptor
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 2: TAR-200 TAR-200 TAR-200 is placed into the bladder through a urinary placement catheter in participants with CIS, with or without papillary disease, on Day 0 and will be dosed Q3W for up to the first 24 weeks (6 months), then every 12 weeks through Week 99 (Year 2). Cohort 4: TAR-200 (Participants with Papillary Disease only) TAR-200 TAR-200 is placed into the bladder through a urinary placement catheter in participants with papillary disease only, on Day 0 and will be dosed Q3W for up to the first 24 weeks (6 months), then every 12 weeks through Week 99 (Year 2). Cohort 1: TAR-200 and Cetrelimab TAR-200 TAR-200 is placed into the bladder through a urinary placement catheter in participants with carcinoma in situ (CIS), with or without papillary disease, on Day 0 and will be dosed every 3 weeks (Q3W) for up to the first 24 weeks (6 months), then every 12 weeks through Week 99 (Year 2). In addition, Cetrelimab will be dosed Q3W through Week 78 (18 months). Cohort 3: Cetrelimab Cetrelimab Participants with CIS, with or without papillary disease, will receive Cetrelimab which will be dosed Q3W through Week 78 (18 months). Cohort 1: TAR-200 and Cetrelimab Cetrelimab TAR-200 is placed into the bladder through a urinary placement catheter in participants with carcinoma in situ (CIS), with or without papillary disease, on Day 0 and will be dosed every 3 weeks (Q3W) for up to the first 24 weeks (6 months), then every 12 weeks through Week 99 (Year 2). In addition, Cetrelimab will be dosed Q3W through Week 78 (18 months).
- Primary Outcome Measures
Name Time Method Cohort 1, 2, and 3: Overall Complete Response (CR) Rate Up to 5 years Overall CR rate is defined as the percentage of participants achieving a CR at any time post-treatment. It will be measured by determining the percentage of participants without presence of high-grade disease using results from cystoscopy and centrally read urine cytology at any time point.
Cohort 4: Disease-free Survival (DFS) Up to 5 years DFS will be measured as the time from the date of first dose of study treatment to either the time of the first recurrence of high-risk disease, progression, or death due to any cause, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Cohort 1 and 3: Serum Concentration of Anti-cetrelimab Antibodies Predose, up to 3 years Serum concentration of anti-cetrelimab antibodies will be assessed using a validated immunoassay for anti-drug antibody (ADA) analysis.
Cohort 1, 2, and 3: Duration of Response (DOR) Up to 5 years DOR is defined from the date of first CR achieved to the date of first evidence of recurrence or progression or death (whichever is earlier) for participants who achieve a CR.
Overall Survival (OS) Up to 5 years OS, defined as the time from the date of first dose of study treatment to death; if a participant has not died at the time of analysis, the participant will be censored at the date last known alive.
Cohort 1, 2, and 4: Concentrations of Gemcitabine and 2',2' difluorodeoxyuridine (dFdU) in Urine and Plasma Up to Week 21 Concentrations of gemcitabine and its metabolite dFdU in urine and plasma will be assessed.
Number of Participants with Anti-cetrelimab Antibodies Predose, up to 3 years Number of participants with anti-cetrelimab antibodies will be reported.
Change from Baseline in European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ) -C30 Scores Baseline, up to 3 years and 4 months EORTC QLQ-C30 is a core 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies. It incorporates 5 functional scales (physical, role, cognitive, emotional, and social functioning), 3 symptom scales (fatigue, pain, and nausea or vomiting), and a global health status or HRQoL scale. Ratings for each item range from 1 (not at all) to 4 (very much).
Change from Baseline in EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24 Scores Baseline, up to 3 years and 4 months EORTC QLQ-NMIBC24 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).
Number of Participants with Adverse Events (AEs) by Severity Grades Up to 5 years An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity grades 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.
Trial Locations
- Locations (143)
Urological Associates of Southern Arizona, P.C.
🇺🇸Tucson, Arizona, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Genesis Healthcare Partners - Genesis Research Greater Los Angeles
🇺🇸Sherman Oaks, California, United States
The Urology Center of Colorado
🇺🇸Denver, Colorado, United States
Foothills Urology - Golden Off
🇺🇸Golden, Colorado, United States
DuPage Medical Group
🇺🇸Lisle, Illinois, United States
Urology of Indiana
🇺🇸Greenwood, Indiana, United States
Wichita Urology Group
🇺🇸Wichita, Kansas, United States
Michigan Institute of Urology
🇺🇸Troy, Michigan, United States
NYU Langone Health
🇺🇸New York, New York, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Associated Medical Professionals
🇺🇸Syracuse, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
The Urology Group
🇺🇸Cincinnati, Ohio, United States
Urologic Consultants of Southeastern Pennsylvania
🇺🇸Bala-Cynwyd, Pennsylvania, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Urology Associates, PC
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Urology Austin
🇺🇸Austin, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Urology San Antonio Research
🇺🇸San Antonio, Texas, United States
Spokane Urology
🇺🇸Spokane, Washington, United States
Flinders Medical Centre
🇦🇺Bedford Park, Australia
Eastern Health Research
🇦🇺Box Hill, Australia
Macquarie University Hospital
🇦🇺Sydney, Australia
Algemeen Ziekenhuis Sint-Jan
🇧🇪Assebroek, Belgium
AZ St.-Jan Brugge-Oostende AV
🇧🇪Brugge, Belgium
Hopital Erasme
🇧🇪Brussel, Belgium
Algemeen ziekenhuis Maria Middelares
🇧🇪Gent, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Algemeen Ziekenhuis Delta
🇧🇪Roeselare, Belgium
AZ Nikolaas
🇧🇪Sint-Niklaas, Belgium
Exdeo Clinical Research Inc
🇨🇦Abbotsford, British Columbia, Canada
William Osler Health System
🇨🇦Brampton, Ontario, Canada
Princess Margaret Hospital- UHN
🇨🇦Toronto, Ontario, Canada
McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
Universite de Sherbrooke
🇨🇦Sherbrooke, Quebec, Canada
Hopital Pellegrin CHU Bordeaux
🇫🇷Bordeaux, France
Polyclinique Bordeaux Nord Acquitaine
🇫🇷Bordeaux, France
CHU Grenoble
🇫🇷Grenoble, France
Clinique Sainte Marguerite
🇫🇷Hyeres, France
Polyclinique de Limoges - Francois Chenieux
🇫🇷Limoges, France
Hôpital Edouard Herriot
🇫🇷Lyon Cedex 03, France
Institut Paoli-Calmettes
🇫🇷Marseille, France
Centre de Cancerologie du Grand Montpellier
🇫🇷Montpellier, France
CHU Nîmes
🇫🇷Nimes, France
Hôpital Universitaire Pitié-Salpêtrière
🇫🇷Paris Cedex 13, France
Hopital Saint Louis
🇫🇷Paris, France
Hopital Europeen Georges-Pompidou
🇫🇷Paris, France
Groupe Hospitalier Diaconesses Croix Saint Simon
🇫🇷Paris, France
Hopital Bichat Claude Bernard
🇫🇷Paris, France
Hopital Pontchaillou
🇫🇷Rennes cedex 9, France
Clinical La Croix Du Sud - Ramsay Santé
🇫🇷Quint-Fonsegrives, France
CHP Saint Gregoire
🇫🇷Saint Gregoire, France
Institut de Cancerologie Strasbourg Europe ICANS
🇫🇷Strasbourg, France
Hopital Foch
🇫🇷Suresnes, France
Hopital Rangueil
🇫🇷Toulouse, France
Urologicum Duisburg
🇩🇪Duisburg, Germany
Klinikum Herne - Urologie
🇩🇪Herne, Germany
Urologische Partnerschaft Koln UPK
🇩🇪Köln, Germany
Matthias Schulze - Germany
🇩🇪Markkleeberg, Germany
Urologie Neandertal Praxis Mettmann
🇩🇪Mettmann, Germany
Universitatsklinikum Munster
🇩🇪Münster, Germany
Studienpraxis Urologie Nürtingen - Germany
🇩🇪Nürtingen, Germany
Schön Klinik Nürnberg Fürth
🇩🇪Nürnberg, Germany
Metropolitan General A E
🇬🇷Holargos, Greece
Athens Medical Center
🇬🇷Maroussi, Greece
Urologische Praxis am Wasserturm - Germany
🇩🇪Würselen, Germany
Bioclinic - Thessaloniki
🇬🇷Thessaloniki, Greece
General Hospital of Thessaloniki G. Gennimatas
🇬🇷Thessaloniki, Greece
Euromedica General Clinic
🇬🇷Thessaloniki, Greece
Papageorgiou General Hospital Of Thessaloniki
🇬🇷Thessaloniki, Greece
Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari
🇮🇹Bari, Italy
Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Italy
Ospedale San Martino
🇮🇹Genova, Italy
Ospedale San Raffaele
🇮🇹Milan, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Azienda Ospedaliera Sant Andrea
🇮🇹Roma, Italy
Istituto Nazionale Tumori Regina Elena
🇮🇹Rome, Italy
Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino
🇮🇹Torino, Italy
Ospedale San Bortolo
🇮🇹Vicenza, Italy
Ospedale di Circolo e Fondazione Macchi
🇮🇹Varese, Italy
Aso Co.,Ltd Iizuka Hospital
🇯🇵Iizuka, Japan
St Marianna University Hospital
🇯🇵Kanagawa, Japan
Nara Medical University Hospital
🇯🇵Kashihara-shi, Japan
Kimitsu Chuo Hospital
🇯🇵Kisarazu-shi, Japan
Nagasaki University Hospital
🇯🇵Nagasaki-shi, Japan
JOHAS Osaka Rosai Hospital
🇯🇵Osaka, Japan
Toranomon Hospital
🇯🇵Tokyo, Japan
Toyama University Hospital
🇯🇵Toyama-shi, Japan
Fujita Health University Hospital
🇯🇵Toyoake, Japan
University of Tsukuba Hospital
🇯🇵Tsukuba-Shi, Japan
Yokohama City University Medical Center
🇯🇵Yokohama, Japan
Inje University Haeundae Paik Hospital
🇰🇷Busan, Korea, Republic of
Kyungpook National University Chilgok Hospital
🇰🇷Daegu, Korea, Republic of
Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
National Cancer Center
🇰🇷Goyang si, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Gangnam Severance Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Seoul St Mary s Hospital
🇰🇷Seoul, Korea, Republic of
Antoni van Leeuwenhoek
🇳🇱Amsterdam, Netherlands
Catharina Ziekenhuis
🇳🇱Eindhoven, Netherlands
Pusan National University Yangsan Hospital
🇰🇷Yangsan Si, Korea, Republic of
Canisius-Wilhelmina Ziekenhuis
🇳🇱Nijmegen, Netherlands
The Julius Center - Utrecht Science Park - Stratenum
🇳🇱Utrecht, Netherlands
Uls Regiao Aveiro - Hosp. Infante D. Pedro
🇵🇹Aveiro, Portugal
Hospital Garcia de Orta
🇵🇹Almada, Portugal
Uls Alto Ave - Hosp. Sra. Da Oliveira Guimaraes
🇵🇹Guimarães, Portugal
Centro Hospitalar de Lisboa Central
🇵🇹Lisboa, Portugal
Fund. Champalimaud
🇵🇹Lisbon, Portugal
Uls Loures Odivelas - Hosp. Loures
🇵🇹Loures, Portugal
Instituto Portugues de Oncologia do Porto Francisco Gentil
🇵🇹Porto, Portugal
Centro Hospitalar de Vila Nova de Gaia Espinho E P E
🇵🇹Vila Nova de Gaia, Portugal
Centro Hospitalar de Trás os Montes e Alto-Douro
🇵🇹Vila Real, Portugal
Hertzen Oncology Research Institute
🇷🇺Moscow, Russian Federation
City Clinical Hospital #1
🇷🇺Nizhny Novgorod, Russian Federation
Avicenna Medical Center
🇷🇺Novosibirsk, Russian Federation
A. Tsyb Medical Radiological Research Center
🇷🇺Obninsk, Russian Federation
BHI of Omsk region Clinical Oncology Dispensary
🇷🇺Omsk, Russian Federation
Ultrasound Clinic 4D
🇷🇺Pyatigorsk, Russian Federation
Saratov State Medical University
🇷🇺Saratov, Russian Federation
Multifunctional clinical medical center 'Medical city'
🇷🇺Tyumen, Russian Federation
Bashkir State Medical University
🇷🇺Ufa, Russian Federation
Hosp Univ A Coruna
🇪🇸A Coruña, Spain
Hosp. Univ. Germans Trias I Pujol
🇪🇸Badalona, Spain
Fund. Puigvert
🇪🇸Barcelona, Spain
Hosp. Puerta Del Mar
🇪🇸Cadiz, Spain
Hosp. Univ. Virgen de Las Nieves
🇪🇸Granada, Spain
Hosp. de Jerez de La Frontera
🇪🇸Jerez De La Frontera, Spain
Hosp. Univ. Ramon Y Cajal
🇪🇸Madrid, Spain
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
Hosp. Univ. La Paz
🇪🇸Madrid, Spain
Hosp. Univ. Hm Monteprincipe
🇪🇸Madrid, Spain
Hosp Virgen de La Victoria
🇪🇸Málaga, Spain
Corporacio Sanitari Parc Tauli
🇪🇸Sabadell, Spain
Sumy Regional Clinical Oncology Centre
🇺🇦Sumy, Ukraine
NHS Greater Glasgow and Clyde
🇬🇧Glasgow, United Kingdom
Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain
Chernihivskyi oblasnyi onkolohichnyi dyspanser
🇺🇦Chernihiv, Ukraine
Asklepion LLC
🇺🇦Kiev, Ukraine
Leeds Teaching Hospitals NHS Trust
🇬🇧Leeds, United Kingdom