Clinical trial NCT04640623: 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
Official title: Phase 2b Clinical Study Evaluating Efficacy and Safety of TAR-200 in Combination With Cetrelimab, TAR-200 Alone, or Cetrelimab Alone in Participants With High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Intravesical Bacillus Calmette-Guérin (BCG) Who Are Ineligible for or Elected Not to Undergo Radical Cystectomy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Urinary Bladder Neoplasms
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-11-23
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Cohort 1, 2, and 3: Overall Complete Response (CR) Rate
timeFrame: Up to 5 years
measure: Cohort 4: Disease-free Survival (DFS)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Cohort 1, 2, and 3: Duration of Response (DOR)
timeFrame: Up to 5 years
measure: Overall Survival (OS)
timeFrame: Up to 5 years
measure: Cohort 1, 2, and 4: Concentrations of Gemcitabine and 2',2' difluorodeoxyuridine (dFdU) in Urine and Plasma
timeFrame: Up to Week 21
measure: Cohort 1 and 3: Serum Concentration of Anti-cetrelimab Antibodies
timeFrame: Predose, up to 3 years
measure: Number of Participants with Anti-cetrelimab Antibodies
timeFrame: Predose, up to 3 years
measure: Change from Baseline in European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ) -C30 Scores
timeFrame: Baseline, up to 3 years and 4 months
measure: Change from Baseline in EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24 Scores
timeFrame: Baseline, up to 3 years and 4 months
measure: Number of Participants with Adverse Events (AEs) by Severity Grades
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Urological Associates of Southern Arizona, P.C.
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Sherman Oaks
country: United States
facility: Genesis Healthcare Partners - Genesis Research Greater Los Angeles
state: California
city: Denver
country: United States
facility: The Urology Center of Colorado
state: Colorado
city: Golden
country: United States
facility: Foothills Urology - Golden Off
state: Colorado
city: Lisle
country: United States
facility: DuPage Medical Group
state: Illinois
city: Greenwood
country: United States
facility: Urology of Indiana
state: Indiana
city: Wichita
country: United States
facility: Wichita Urology Group
state: Kansas
city: Troy
country: United States
facility: Michigan Institute of Urology
state: Michigan
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Syracuse
country: United States
facility: Associated Medical Professionals
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Cincinnati
country: United States
facility: The Urology Group
state: Ohio
city: Bala-Cynwyd
country: United States
facility: Urologic Consultants of Southeastern Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Nashville
country: United States
facility: Urology Associates, PC
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Urology Austin
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: San Antonio
country: United States
facility: Urology San Antonio Research
state: Texas
city: Spokane
country: United States
facility: Spokane Urology
state: Washington
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
city: Box Hill
country: Australia
facility: Eastern Health Research
city: Sydney
country: Australia
facility: Macquarie University Hospital
city: Assebroek
country: Belgium
facility: Algemeen Ziekenhuis Sint-Jan
city: Brugge
country: Belgium
facility: AZ St.-Jan Brugge-Oostende AV
city: Brussel
country: Belgium
facility: Hopital Erasme
city: Gent
country: Belgium
facility: Algemeen ziekenhuis Maria Middelares
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Roeselare
country: Belgium
facility: Algemeen Ziekenhuis Delta
city: Sint-Niklaas
country: Belgium
facility: AZ Nikolaas
city: Abbotsford
country: Canada
facility: Exdeo Clinical Research Inc
state: British Columbia
city: Brampton
country: Canada
facility: William Osler Health System
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital- UHN
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Sherbrooke
country: Canada
facility: Universite de Sherbrooke
state: Quebec
city: Bordeaux
country: France
facility: Hopital Pellegrin CHU Bordeaux
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Acquitaine
city: Grenoble
country: France
facility: CHU Grenoble
city: Hyeres
country: France
facility: Clinique Sainte Marguerite
city: Limoges
country: France
facility: Polyclinique de Limoges - Francois Chenieux
city: Lyon Cedex 03
country: France
facility: Hôpital Edouard Herriot
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Montpellier
country: France
facility: Centre de Cancerologie du Grand Montpellier
city: Nimes
country: France
facility: CHU Nimes
city: Paris Cedex 13
country: France
facility: Hôpital Universitaire Pitié-Salpêtrière
city: Paris
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Hopital Europeen Georges-Pompidou
city: Paris
country: France
facility: Groupe Hospitalier Diaconesses Croix Saint Simon
city: Paris
country: France
facility: Hopital Bichat Claude Bernard
city: Quint-Fonsegrives
country: France
facility: Clinical La Croix Du Sud - Ramsay Santé
city: Rennes cedex 9
country: France
facility: Hopital Pontchaillou
city: Saint Gregoire
country: France
facility: CHP Saint Gregoire
city: Strasbourg
country: France
facility: Institut de Cancerologie Strasbourg Europe ICANS
city: Suresnes
country: France
facility: Hopital Foch
city: Toulouse
country: France
facility: Hopital Rangueil
city: Duisburg
country: Germany
facility: Urologicum Duisburg
city: Herne
country: Germany
facility: Klinikum Herne - Urologie
city: Köln
country: Germany
facility: Urologische Partnerschaft Koln UPK
city: Markkleeberg
country: Germany
facility: Matthias Schulze - Germany
city: Mettmann
country: Germany
facility: Urologie Neandertal Praxis Mettmann
city: Münster
country: Germany
facility: Universitatsklinikum Munster
city: Nürnberg
country: Germany
facility: Schön Klinik Nürnberg Fürth
city: Nürtingen
country: Germany
facility: Studienpraxis Urologie Nürtingen - Germany
city: Würselen
country: Germany
facility: Urologische Praxis am Wasserturm - Germany
city: Holargos
country: Greece
facility: Metropolitan General A E
city: Maroussi
country: Greece
facility: Athens Medical Center
city: Thessaloniki
country: Greece
facility: Bioclinic - Thessaloniki
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki G. Gennimatas
city: Thessaloniki
country: Greece
facility: Euromedica General Clinic
city: Thessaloniki
country: Greece
facility: Papageorgiou General Hospital Of Thessaloniki
city: Bari
country: Italy
facility: Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari
city: Bari
country: Italy
facility: Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Genova
country: Italy
facility: Ospedale San Martino
city: Milan
country: Italy
facility: Ospedale San Raffaele
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant Andrea
city: Rome
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
city: Torino
country: Italy
facility: Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi
city: Vicenza
country: Italy
facility: Ospedale San Bortolo
city: Iizuka
country: Japan
facility: Aso Co.,Ltd Iizuka Hospital
city: Kanagawa
country: Japan
facility: St Marianna University Hospital
city: Kashihara-shi
country: Japan
facility: Nara Medical University Hospital
city: Kisarazu-shi
country: Japan
facility: Kimitsu Chuo Hospital
city: Nagasaki-shi
country: Japan
facility: Nagasaki University Hospital
city: Osaka
country: Japan
facility: JOHAS Osaka Rosai Hospital
city: Tokyo
country: Japan
facility: Toranomon Hospital
city: Toyama-shi
country: Japan
facility: Toyama University Hospital
city: Toyoake
country: Japan
facility: Fujita Health University Hospital
city: Tsukuba-Shi
country: Japan
facility: University of Tsukuba Hospital
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Goyang si
country: Korea, Republic of
facility: National Cancer Center
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St Mary s Hospital
city: Yangsan Si
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Nijmegen
country: Netherlands
facility: Canisius-Wilhelmina Ziekenhuis
city: Utrecht
country: Netherlands
facility: The Julius Center - Utrecht Science Park - Stratenum
city: Almada
country: Portugal
facility: Hospital Garcia de Orta
city: Aveiro
country: Portugal
facility: Uls Regiao Aveiro - Hosp. Infante D. Pedro
city: Guimarães
country: Portugal
facility: Uls Alto Ave - Hosp. Sra. Da Oliveira Guimaraes
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Central
city: Lisbon
country: Portugal
facility: Fund. Champalimaud
city: Loures
country: Portugal
facility: Uls Loures Odivelas - Hosp. Loures
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia do Porto Francisco Gentil
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia Espinho E P E
city: Vila Real
country: Portugal
facility: Centro Hospitalar de Trás os Montes e Alto-Douro
city: Moscow
country: Russian Federation
facility: Hertzen Oncology Research Institute
city: Nizhny Novgorod
country: Russian Federation
facility: City Clinical Hospital #1
city: Novosibirsk
country: Russian Federation
facility: Avicenna Medical Center
city: Obninsk
country: Russian Federation
facility: A. Tsyb Medical Radiological Research Center
city: Omsk
country: Russian Federation
facility: BHI of Omsk region Clinical Oncology Dispensary
city: Pyatigorsk
country: Russian Federation
facility: Ultrasound Clinic 4D
city: Saratov
country: Russian Federation
facility: Saratov State Medical University
city: Tyumen
country: Russian Federation
facility: Multifunctional clinical medical center 'Medical city'
city: Ufa
country: Russian Federation
facility: Bashkir State Medical University
city: A Coruña
country: Spain
facility: Hosp Univ A Coruna
city: Badalona
country: Spain
facility: Hosp. Univ. Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Fund. Puigvert
city: Cadiz
country: Spain
facility: Hosp. Puerta Del Mar
city: Granada
country: Spain
facility: Hosp. Univ. Virgen de Las Nieves
city: Jerez De La Frontera
country: Spain
facility: Hosp. de Jerez de La Frontera
city: Madrid
country: Spain
facility: Hosp. Univ. Ramon Y Cajal
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Madrid
country: Spain
facility: Hosp. Univ. La Paz
city: Madrid
country: Spain
facility: Hosp. Univ. Hm Monteprincipe
city: Málaga
country: Spain
facility: Hosp Virgen de La Victoria
city: Sabadell
country: Spain
facility: Corporacio Sanitari Parc Tauli
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
city: Chernihiv
country: Ukraine
facility: Chernihivskyi oblasnyi onkolohichnyi dyspanser
city: Kiev
country: Ukraine
facility: Asklepion LLC
city: Sumy
country: Ukraine
facility: Sumy Regional Clinical Oncology Centre
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: