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

Urinary Bladder Neoplasms Clinical Trial

— SunRISe-1  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04640623
• Other study ID #: CR108921
• Secondary ID: 2020-002646-1617
• Status: Recruiting
• Phase: Phase 2
• Start date: December 18, 2020
• Est. completion date: July 2, 2027

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: July 2, 2027
• Est. primary completion date: November 20, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Urinary Bladder Neoplasms

Intervention

Drug:
• TAR-200
TAR-200 will be administered transuretherally.

Biological:
• Cetrelimab
Cetrelimab will be administered.

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park
Australia	Eastern Health Research	Box Hill
Australia	Macquarie University Hospital	Sydney
Belgium	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
Canada	Exdeo Clinical Research Inc	Abbotsford	British Columbia
Canada	William Osler Health System	Brampton	Ontario
Canada	McGill University Health Centre	Montreal	Quebec
Canada	Universite de Sherbrooke	Sherbrooke	Quebec
Canada	Princess Margaret Hospital- UHN	Toronto	Ontario
France	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	Groupe Hospitalier Diaconesses Croix Saint Simon	Paris
France	Hopital Bichat Claude Bernard	Paris
France	Hopital Europeen Georges-Pompidou	Paris
France	Hopital Saint Louis	Paris
France	Hôpital Universitaire Pitié-Salpêtrière	Paris Cedex 13
France	Clinical La Croix Du Sud - Ramsay Santé	Quint-Fonsegrives
France	Hopital Pontchaillou	Rennes cedex 9
France	CHP Saint Gregoire	Saint Gregoire
France	Institut de Cancerologie Strasbourg Europe ICANS	Strasbourg
France	Hopital Foch	Suresnes
France	Hopital Rangueil	Toulouse
Germany	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	Schön Klinik Nürnberg Fürth	Nürnberg
Germany	Studienpraxis Urologie Nürtingen - Germany	Nürtingen
Germany	Urologische Praxis am Wasserturm - Germany	Würselen
Greece	Metropolitan General A E	Holargos
Greece	Athens Medical Center	Maroussi
Greece	Bioclinic - Thessaloniki	Thessaloniki
Greece	Euromedica General Clinic	Thessaloniki
Greece	General Hospital of Thessaloniki G. Gennimatas	Thessaloniki
Greece	Papageorgiou General Hospital Of Thessaloniki	Thessaloniki
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 di Circolo e Fondazione Macchi	Varese
Italy	Ospedale San Bortolo	Vicenza
Japan	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
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	The Catholic University of Korea Seoul St Mary s Hospital	Seoul
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan Si
Netherlands	NKI AVL Amsterdam	Amsterdam
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	Canisius-Wilhelmina Ziekenhuis	Nijmegen
Netherlands	The Julius Center - Utrecht Science Park - Stratenum	Utrecht
Portugal	Hospital Garcia de Orta	Almada
Portugal	Chbv - Hosp. Infante D. Pedro	Aveiro
Portugal	Hosp. Sra. Da Oliveira - Guimaraes	Guimarães
Portugal	Centro Hospitalar de Lisboa Central	Lisboa
Portugal	Fund. Champalimaud	Lisbon
Portugal	Hospital Beatriz Angelo	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
Russian Federation	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
Spain	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. 12 de Octubre	Madrid
Spain	Hosp. Univ. Hm Monteprincipe	Madrid
Spain	Hosp. Univ. La Paz	Madrid
Spain	Hosp. Univ. Ramon Y Cajal	Madrid
Spain	Hosp. Virgen de La Victoria	Málaga
Spain	Corporacio Sanitari Parc Tauli	Sabadell
Spain	Instituto Valenciano de Oncologia	Valencia
Ukraine	Chernihivskyi oblasnyi onkolohichnyi dyspanser	Chernihiv
Ukraine	Asklepion LLC	Kiev
Ukraine	Sumy Regional Clinical Oncology Centre	Sumy
United Kingdom	NHS Greater Glasgow and Clyde	Glasgow
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds
United States	Urology Austin	Austin	Texas
United States	Urologic Consultants of Southeastern Pennsylvania	Bala-Cynwyd	Pennsylvania
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	The Urology Group	Cincinnati	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	The Urology Center of Colorado	Denver	Colorado
United States	Foothills Urology - Golden Off	Golden	Colorado
United States	Urology of Indiana	Greenwood	Indiana
United States	DuPage Medical Group	Lisle	Illinois
United States	University of Southern California	Los Angeles	California
United States	Urology Associates, PC	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	NYU Langone Health	New York	New York
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Urology San Antonio Research	San Antonio	Texas
United States	Genesis Healthcare Partners - Genesis Research Greater Los Angeles	Sherman Oaks	California
United States	Spokane Urology	Spokane	Washington
United States	Associated Medical Professionals	Syracuse	New York
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Michigan Institute of Urology	Troy	Michigan
United States	Urological Associates of Southern Arizona, P.C.	Tucson	Arizona
United States	Wichita Urology Group	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Greece,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Portugal,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort 1, 2, and 3: Overall Complete Response (CR) Rate	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.	Up to 5 years
Primary	Cohort 4: Disease-free Survival (DFS)	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.	Up to 5 years
Secondary	Cohort 1, 2, and 3: Duration of Response (DOR)	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.	Up to 5 years
Secondary	Overall Survival (OS)	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.	Up to 5 years
Secondary	Cohort 1, 2, and 4: Concentrations of Gemcitabine and 2',2' difluorodeoxyuridine (dFdU) in Urine and Plasma	Concentrations of gemcitabine and its metabolite dFdU in urine and plasma will be assessed.	Up to Week 21
Secondary	Cohort 1 and 3: Serum Concentration of Anti-cetrelimab Antibodies	Serum concentration of anti-cetrelimab antibodies will be assessed using a validated immunoassay for anti-drug antibody (ADA) analysis.	Predose, up to 3 years
Secondary	Number of Participants with Anti-cetrelimab Antibodies	Number of participants with anti-cetrelimab antibodies will be reported.	Predose, up to 3 years
Secondary	Change from Baseline in European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ) -C30 Scores	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).	Baseline, up to 3 years and 4 months
Secondary	Change from Baseline in EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24 Scores	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).	Baseline, up to 3 years and 4 months
Secondary	Number of Participants with Adverse Events (AEs) by Severity Grades	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.	Up to 5 years