A Study of TAR-200 in Combination With Cetrelimab and Cetrelimab Alone in Participants With Muscle-Invasive Urothelial Carcinoma of the Bladder

Urinary Bladder Neoplasms Clinical Trial

— SunRISe-4  

Official title:

A Phase 2, Open-Label, Multi-Center, Randomized Study of TAR-200 in Combination With Cetrelimab and Cetrelimab Alone in Participants With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Scheduled for Radical Cystectomy and Are Ineligible for or Refusing Platinum-Based Neoadjuvant Chemotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04919512
• Other study ID #: CR109044
• Secondary ID: 2020-005565-1317
• Status: Recruiting
• Phase: Phase 2
• Start date: July 7, 2022
• Est. completion date: March 16, 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 anti-tumor effects of TAR-200 in combination with intravenous (IV) cetrelimab and IV cetrelimab alone.

Description:

Bladder cancer is the tenth most common malignancy worldwide. Approximately 25 percent (%) of all new bladder cancer participants present with muscle invasive bladder cancer (MIBC) at the time of diagnosis, and roughly 50% will ultimately develop distant metastases. The TAR-200/ gemcitabine (JNJ-17000139) product is an intravesical drug delivery system regulated as an investigational drug. The drug constituent consists of gemcitabine minitablets 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 standard of care in MIBC includes radical cystectomy (RC) with urinary diversion and is considered the preferred treatment option for participants who are considered surgical candidates. Study consists of a Screening phase, Treatment phase and follow-up phase. The total duration of study will be up to 2 years and 6 months. Efficacy, safety, pharmacokinetics (PK), and biomarkers will be assessed at specific time points during this study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: March 16, 2027
• Est. primary completion date: December 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically proven, cT2-T4a N0, M0 infiltrating urothelial carcinoma of the bladder. Initial diagnosis must have been within 120 days of randomization date. Participants with variant histologic subtypes are allowed if tumor(s) demonstrate urothelial predominance. However, the presence of small cell or neuroendocrine variants will make a participant ineligible

• Participants with no residual tumor, or intravesical tumor size of less than or equal to (<=)3 centimeter (cm) following transurethral resection of bladder tumor (TURBT) are eligible; debulking TURBT for any residual disease is encouraged but not mandated. Participants with persistent tumors greater than (>)3 cm at screening must undergo a second debulking, re-staging TURBT. Participants will be ineligible if any individual tumor is >3 cm after debulking TURBT

• Deemed eligible for and willing to undergo RC by the operating urologist

• Eastern Cooperative Oncology Group (ECOG) performance status Grade 0 or 1

• Thyroid function tests within normal range or stable on hormone supplementation per investigator assessment. Investigators may consult an endocrinologist for participant eligibility assessment in the case of equivocal or marginal tests results

• All adverse events associated with any prior surgery must have resolved to common terminology criteria for adverse events (CTCAE) version 5.0 Grade less than (<) 2 prior to randomization

Exclusion Criteria:

• Must not have received prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to starting study treatment

• Participants must not have evidence of cT4b, or N1-3, or M1 disease based on central radiology staging (chest, abdomen, and pelvis must be performed using computed tomography [CT] or magnetic resonance imaging [MRI]) within 42 days prior to randomization

• Presence of any bladder or urethral anatomic feature that, in the opinion of the Investigator, may prevent the safe placement, indwelling use, or removal of TAR-200

• Prior systemic chemotherapy for urothelial cell carcinoma of the bladder at any time

• Currently participating or has participated in a study of an investigational agent and received study therapy or investigational device within 4 weeks prior to enrollment

• Participants with evidence of bladder perforation during diagnostic cystoscopy. Participant is eligible if perforation has resolved prior to dosing

Related Conditions & MeSH terms

• Carcinoma, Transitional Cell
• Urinary Bladder Neoplasms

Intervention

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

Biological:
• Cetrelimab
Cetrelimab will be administered.

Locations

Country	Name	City	State
Belgium	Algemeen Ziekenhuis Sint-Jan	Brugge
Belgium	AZ Sint-Jan Brugge-Oostende AV	Brugge
Belgium	Ziekenhuis Oost-Limburg	Genk
Belgium	Hopital de Jolimont	Haine Saint Paul La Louviere
Belgium	ZNA Jan Palfijn	Merksem
Belgium	Centre Interuniversitaire Ambroise Pare - Ambroise Paré	Mons
France	Clinique Tivoli Ducos	Bordeaux
France	ICH Hopital A. Morvan	Brest
France	Hopital Henri Mondor	Creteil
France	Hôpital Privé Le Bois	Lille
France	Polyclinique de Limoges - Francois Chenieux	Limoges
France	Hopital de la Timone	Marseille
France	CHU Montpellier	Montpellier
France	CHU Nîmes	Nimes
France	Hopital Europeen Georges-Pompidou	Paris
France	Hopital Bichat Claude Bernard	Paris Cedex 18
France	Hospices Civils de Lyon HCL	Pierre Bénite
France	Clinical La Croix Du Sud - Ramsay Santé	Quint-Fonsegrives
France	HIA se Sainte-Anne - Toulon	Toulon
France	Clinique Pasteur	Toulouse
Germany	Vivantes Klinikum Am Urban	Berlin-Kreuzberg
Germany	Staedtisches Klinikum Braunschweig	Braunschweig
Germany	Agaplesion Frankfurter Diakonie Kliniken GmbH, Markus Krankenhaus	Frankfurt am Main
Germany	Universitaetsklinikum Halle Saale	Halle Saale
Germany	Marien hospital Herne	Herne
Germany	Universitatsklinikum Munster	Muenster
Israel	Carmel Medical Center	Haifa
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Rabin Medical Center - Hasharon Hospital	Petah Tikva
Israel	The Chaim Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv Yafo
Italy	Ospedale San Giuseppe Moscati di Avellino	Avellino
Italy	Ospedale Civile Ramazzini	Carpi
Italy	SPDC Villa Scassi	Genova
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	Istituto Dei Tumori Di Milano	Milano
Italy	Istituto Europeo di Oncologia	Milano
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	ASL Napoli 2 Nord-SM delle Grazie Hospital	Pozzuoli
Italy	Istituto Nazionale Tumori Regina Elena	Roma
Italy	IRCCS Istituto Clinico Humanitas	Rozzano
Italy	Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino	Torino
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	Samsung Medical Center	Gangnam Gu
Korea, Republic of	National Cancer Center	Goyang-Si
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Korea University Anam 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	Ziekenhuisgroep Twente	Almelo
Netherlands	Haga ziekenhuis	Den Haag
Netherlands	Canisius-Wilhelmina Ziekenhuis	Nijmegen
Netherlands	Radboud Umcn	Nijmegen
Spain	Hosp. Univ. A Coruna	A Coruna
Spain	Fund. Puigvert	Barcelona
Spain	Hosp. Univ. San Cecilio	Granada
Spain	Clinica Univ. de Navarra	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hosp. Virgen de La Victoria	Málaga
Spain	Hosp. Univ. Marques de Valdecilla	Santander
United Kingdom	Barts Health NHS Trust	London
United Kingdom	Lancashire Teaching Hospitals NHS Foundation Trust Royal Preston Hospital	Preston
United States	Mount Sinai Queens Infusion Center	Astoria	New York
United States	Winship Cancer Institute Emory University	Atlanta	Georgia
United States	MidLantic Urology	Bala-Cynwyd	Pennsylvania
United States	Penn Medicine - PerelmanCenter for Advanced Medicine	Baltimore	Maryland
United States	University Of Maryland Medical Center	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Ellis Fischel Cancer Center	Columbia	Missouri
United States	The Ohio State University	Columbus	Ohio
United States	City of Hope	Duarte	California
United States	Colorodo Urology- St. Anthony Hospital	Golden	Colorado
United States	Houston Metro Urology	Houston	Texas
United States	Urology of Indiana	Indianapolis	Indiana
United States	Mayo Clinic	Jacksonville	Florida
United States	University of Florida Health Jacksonville	Jacksonville	Florida
United States	First Urology	Jeffersonville	Indiana
United States	DuPage Medical Group	Lisle	Illinois
United States	Arkansas Urology	Little Rock	Arkansas
United States	UAMS Winthrop P. Rockefeller Cancer Institute	Little Rock	Arkansas
United States	University of Louisville - James Graham Brown Cancer Center	Louisville	Kentucky
United States	Baptist Hospital of Miami	Miami	Florida
United States	University Of Minnesota	Minneapolis	Minnesota
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Urology Associates	Nashville	Tennessee
United States	Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	New York University Langone Medical Center	New York	New York
United States	University of Pittsburgh Medical Center (UPMC) - Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	David C. Pratt Cancer Center	Saint Louis	Missouri
United States	Washington University School Of Medicine - Center For Advanced Medicine (CAM)	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Urology San Antonio Research	San Antonio	Texas
United States	Genesis Research	San Diego	California
United States	University of Washington School of Medicine	Seattle	Washington
United States	Associated Medical Professionals	Syracuse	New York
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Michigan Institute of Urology, PC	Troy	Michigan
United States	Urological Associates of Southern Arizona, P.C.	Tucson	Arizona
United States	Wake Forest University Baptist Medical Center (WFUBMC) - Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Pathologic Complete Response (pCR)	Percentage of participants with a pathologic complete response (pCR) or no evidence of pathologic intravesical disease and nodal involvement (ypT0N0) derived from analysis of radical cystectomy (RC) bladder specimen will be reported.	Up to Week 15
Secondary	Recurrence-Free Survival (RFS)	RFS is defined as the time from first dose of any study treatment to first radiologic (as assessed by response evaluation criteria in solid tumors [RECIST] 1.1 criteria) or histologic evidence of nodal or metastatic disease or death due to any cause.	Up to Week 108
Secondary	Number of Participants with Adverse Events (AEs) by Grades According to Common Terminology Criteria for Adverse Events (CTCAE)	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.	Up to Week 108
Secondary	Number of Participants with Change from Baseline in Laboratory Abnormalities	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.	Up to Week 108