A Study of TAR-200 in Combination With Cetrelimab and Cetrelimab Alone in Participants With Muscle-Invasive Urothelial Carcinoma of the Bladder (SunRISe-4)

• ClinicalTrials.gov Identifier: NCT04919512
• Recruitment Status: Recruiting
• First Posted: June 9, 2021
• Last Update Posted: March 24, 2023
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: June 8, 2021
• First Posted Date: June 9, 2021
• Last Update Posted Date: March 24, 2023
• Actual Study Start Date: July 7, 2022
• Estimated Primary Completion Date: April 10, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 8, 2021)

Percentage of Participants with Pathologic Complete Response (pCR) [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 21, 2022)

• Recurrence-Free Survival (RFS) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: June 8, 2021)

• Recurrence-Free Survival (RFS) [ Time Frame: Up to Week 108 ]
  RFS is defined as the time from randomization 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) [ Time Frame: 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 [ Time Frame: 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of TAR-200 in Combination With Cetrelimab and Cetrelimab Alone in Participants With Muscle-Invasive Urothelial Carcinoma of the Bladder
• 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
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Urinary Bladder Neoplasms

Intervention

• Drug: TAR-200
  TAR-200 will be administered.
  Other Name: JNJ-17000139
• Biological: Cetrelimab
  Cetrelimab will be administered.
  Other Name: JNJ-63723283

Study Arms

• Experimental: Cohort 1: TAR-200 + Cetrelimab
  Participants will receive TAR-200 in combination with cetrelimab.
  Interventions:

  • Drug: TAR-200
  • Biological: Cetrelimab
• Experimental: Cohort 2: Cetrelimab
  Participants will receive cetrelimab.
  Intervention: Biological: Cetrelimab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 8, 2021): 160
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 17, 2025
• Estimated Primary Completion Date: April 10, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically proven, cT2-T4a N0, M0 infiltrating urothelial carcinoma of the bladder. Initial diagnosis must have been within 90 days of randomization date. Participants with variant histologic subtypes (example squamous differentiation) are allowed if urothelial (transitional cell) differentiation is predominant (example, less than [<]20 percent [%] variant histologic subtype). However, the presence of any neuroendocrine, micropapillary, signet ring cell, plasmacytoid, or sarcomatoid features will make a participant ineligible
• Participants with an individual intravesical tumor size of less than or equal to <=3 centimeter (cm) following transurethral resection of bladder tumor (TURBT) are eligible. Participants with persistent multifocal tumors at screening must undergo a second debulking, re-staging TURBT to reduce the tumor burden. Participants will be ineligible if any individual tumor is greater than (>)3 cm
• 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 date of 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 local 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

• Listed Location Countries: Belgium, France, Israel, Italy, Korea, Republic of, Spain, United Kingdom, United States
• Removed Location Countries: Germany, Netherlands

Administrative Information

• NCT Number: NCT04919512
• Other Study ID Numbers: CR109044; 2020-005565-13 ( EudraCT Number ); 17000139BLC2002 ( Other Identifier: Janssen Research & Development, LLC )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
• URL: https://www.janssen.com/clinical-trials/transparency

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: March 2023