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-Guerin who are Ineligible for or Elected Not to Undergo Radical Cystectomy
- Conditions
- Bladder Cancer
- Registration Number
- JPRN-jRCT2071200086
- Lead Sponsor
- Fujikawa Ei
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 200
Histologically confirmed diagnosis of persistent or recurrent high-risk, non-muscle invasive bladder cancer (HR-NMIBC) (carcinoma in situ [CIS]; Tumour 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 adequate Bacillus Calmette-Guerin (BCG) therapy , in participants who have received adequate BCG. Mixed histology tumours are allowed if urothelial differentiation (transitional cell histology) is predominant (example, less than (<) 20 percent (%) variant histologic subtype). 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 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
- 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 nephrouretrectomy more than 24 months prior to randomization
- Participants with an active, known or suspected autoimmune disease. Participants with autoimmune disorders not requiring systemic treatment (example, skin conditions such as vitiligo, psoriasis, alopecia) or conditions requiring hormonal replacement therapies such as type 1 diabetes mellitus or hypothyroidism are permitted to enroll
- 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Cohort 1, 2, and 3:Overall Complete Clinical Response (CR) Rate<br><br>Up to 5 years<br><br>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.<br><br>Cohort 4:Disease-free Survival (DFS)<br><br>Up to 5 years<br><br>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.
- Secondary Outcome Measures
Name Time Method