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

Phase 2

Active, not recruiting

• Conditions: Urinary Bladder Neoplasms
• Interventions: Biological: Cetrelimab; Drug: TAR-200

• Registration Number: NCT04919512
• Lead Sponsor: Janssen Research & Development, LLC

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2021-06-08
• Study First Submitted QC: 2021-06-08
• Study First Posted: 2021-06-09
• Study Start: 2022-07-07
• Primary Completion: 2025-01-31
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-17
• Last Update Posted: 2025-07-18
• Study Completion: 2027-03-07

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 163

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 2: Cetrelimab	Cetrelimab	Participants will receive cetrelimab.
Cohort 1: TAR-200 + Cetrelimab	TAR-200	Participants will receive TAR-200 in combination with cetrelimab.
Cohort 1: TAR-200 + Cetrelimab	Cetrelimab	Participants will receive TAR-200 in combination with cetrelimab.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants with Pathologic Complete Response (pCR)	Up to Week 15	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.

Secondary Outcome Measures

Name	Time	Method
Recurrence-Free Survival (RFS)	Up to Week 108	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.
Number of Participants with Adverse Events (AEs) by Grades According to Common Terminology Criteria for Adverse Events (CTCAE)	Up to Week 108	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 Change from Baseline in Laboratory Abnormalities	Up to Week 108	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.

Trial Locations

Locations (108)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Urological Associates of Southern Arizona, P.C.; 🇺🇸 Tucson, Arizona, United States

UAMS Winthrop P. Rockefeller Cancer Institute; 🇺🇸 Little Rock, Arkansas, United States

Arkansas Urology; 🇺🇸 Little Rock, Arkansas, United States

City of Hope; 🇺🇸 Duarte, California, United States

Genesis Research; 🇺🇸 San Diego, California, United States

Colorodo Urology- St. Anthony Hospital; 🇺🇸 Golden, Colorado, United States

University of Florida Health Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Baptist Hospital of Miami; 🇺🇸 Miami, Florida, United States

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