Non-Muscle-Invasive Urothelial Carcinoma (NMIBC) of the Bladder MedDRA version: 20.0 Level: LLT Classification code 10046714 Term: Urothelial carcinoma bladder System Organ Class: 100000004864 MedDRA version: 21.0 Level: LLT Classification code 10046720 Term: Urothelial carcinoma bladder stage II System Organ Class: 100000004864 MedDRA version: 21.0 Level: LLT Classification code 10046721 Term: Urothelial carcinoma bladder stage III System Organ Class: 100000004864 MedDRA version: 21.0 Level
Conditions
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years male or female (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent. 2. Histologically confirmed diagnosis of high-risk, non-muscle invasive urothelial carcinoma in situ (CIS; Tis) [AJCC, 2017], with or without papillary disease (T1, high-grade Ta) within 12 months of completion of adequate BCG therapy. 3. Visible papillary disease must be fully resected (absent) prior to randomization (residual CIS acceptable) and documented at screening cystoscopy. 4. Participants must be willing to undergo all study procedures (e.g., multiple cystoscopies from Screening through the end of study and TURBT/bladder biopsy for assessment of recurrence/progression). 5. Participants must be ineligible for or have elected not to undergo radical cystectomy. 6. BCG-unresponsive high-risk NMIBC after treatment with adequate BCG therapy defined as a minimum of 5 of 6 doses of an induction course (adequate induction) plus 2 of 3 doses of a maintenance course, or 2 of 6 doses of a second induction course. 7. All adverse events associated with any prior surgery and/or intravesical therapy must have resolved to CTCAE version 5.0 Grade =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Histologically confirmed, muscle-invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (i.e., T2, T3, T4, and/or Stage IV). 2. Concurrent extra-vesical (i.e., urethra, ureter, or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium. 3. Active malignancies (i.e., progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. 4. 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. 5. Evidence of bladder perforation during diagnostic cystoscopy. 6. Bladder post-void residual (PVR) volume > 350mL at Screening after second voided urine. 7. Participants should not have a history of acute ischemic heart disease within 30 days of cohort assignment, or history of uncontrolled cardiovascular disease. 8. A history of clinically significant polyuria with recorded 24-hour urine volumes greater than 4000 mL. 9. Participants with an active, known or suspected autoimmune disease. Participants with autoimmune disorders not requiring systemic treatment (e.g. 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. 10. Received a live virus vaccine within 30 days of planned start of study treatment. 11. Active infection requiring systemic therapy. 12. Has had an allogeneic tissue/solid organ transplant. 13. Currently participating or has participated in a study of an investigational agent and received study therapy or investigational device within 4 weeks prior to screening. 14. Indwelling catheters are not permitted; however, intermittent catheterization is acceptable. 15. Received intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy/Transurethral Resection of Bladder Tumor (TURBT) to starting study treatment. Immediate post-operative intravesical chemotherapy prior to signing the ICF is allowed per local standard of care. 16. 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. 17. Participants with a history of Grade =3 toxic effects when using anti-TNF or anti-IL-6 agents are excluded. 18. Not recovered from toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration). 19. Participants who require immunosuppressive medications including but not limited to systemic corticosteroid at doses >10 mg/day of prednisone or its equivalence, methotrexate, cyclosporine, azathioprine, and TNF a blockers. 20. Participants must not have clinically significant liver disease that precludes participant treatment regimens prescribed on the study. 21. Known human immunodeficiency virus (HIV) infection, unless the participant has been on a stable anti-retroviral therapy regimen for the last 6 months or more and has had no opportunistic infections and a CD4 count of >350 in the last 6 months. 22. Known active hepatitis B or C infection. 23. Concurrent urinary tract infection (UTI), defined as a symptomatic infection with a positive urine culture with a bacterial count of =105 colony forming units (CFU)/mL in urine voided from women, or >104 CFU/mL in urine voided from men, or in straight-catheter urine from women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: - To evaluate the durability of CR in participants treated with TAR-200 in combination with cetrelimab (Cohort 1), or TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3) with CIS (with or without concomitant Ta or T1 papillary disease) who achieve a CR. - To determine the overall survival (OS) in all participants. - To evaluate the pharmacokinetics (PK) of gemcitabine and major metabolite 2’,2’-difluorodeoxyuridine (dFdU) in urine and plasma in TAR-200 in combination with cetrelimab (Cohort 1), or TAR-200 alone (Cohort 2). - To evaluate the PK and immunogenicity of cetrelimab in serum in combination with TAR-200 (Cohort 1), or cetrelimab alone (Cohort 3). - To evaluate health-related quality of life (HRQoL) in all participants. - To assess the safety and tolerability of participants receiving TAR-200 in combination with cetrelimab (Cohort 1), or TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3).;Primary end point(s): Overall CR rate will be measured by determining the proportion of participants without presence of high-grade disease using results from cystoscopy and centrally read urine cytology at any time point.;Timepoint(s) of evaluation of this end point: date of disease progression/death | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Durability of response. - OS - Gemcitabine and dFdU concentrations in urine and plasma. - Serum concentration and incidence of anti-cetrelimab antibodies. - Change from baseline and time to symptom deterioration in EORTC QLQ-C30 and EORTC QLQ-NMIBC24. - Frequency and grade of adverse events (AEs) (according to Common Terminology Criteria for Adverse Events [CTCAE] version 5). - Laboratory abnormalities: CTCAE grades comparing baseline to the worst post-baseline value; other safety data, such as vital signs, will be considered as appropriate. - assessment of product quality compliants.;Timepoint(s) of evaluation of this end point: - 12 months after achievement of a CR - date of disease progression/death - Week 24 and 48 | — |
Countries
Australia, Belgium, Canada, European Union, France, Germany, Greece, Italy, Japan, Korea, Republic of, Netherlands, Portugal, Russian Federation, Spain, Turkey, Ukraine, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International NV
Outcome results
None listed