A research study of an investigational drug delivery system for adults with high-risk non-muscle invasive bladder cancer

INTERVENTION: Group A: Participants will receive TAR‐200 (225 mg gemcitabine intravesical drug delivery system) every 3 weeks through Week 24 (8 induction doses), with the last with the last TAR‐200 insertion at Week 21 and removal at Week 24. Maintenance dosing (si Xdoses) of TAR‐200 will then occur every 12 weeks. Beginning at week 36, through Week 99 (Year 2), with the last TAR‐200 insertion at Week 96 and removal at Week 99. TAR‐200 drug delivery system containing 225 mg gemcitabine will be administered to the participant intravesically Group B: For participants in Group B, Mitomycin C (MMC) or gemcitabine will be dosed weekly through Week 5 (6 induction doses). Maintenance dosing (10 doses) of MMC or gemcitabine will then occur QM, beginning at Week 8, through Week 44. This may be followed by an optional second year of additional maintenance at the Investigator’s discretion. Gemcitabine (2000 mg) or MMC (40 mg) will be administered to the participant intravesically CONDITION: Recurrent high‐risk non‐muscle‐invasive bladder cancer ; Cancer PRIMARY OUTCOME: Disease‐free survival (DFS), measured as the time from randomisation to the time of the first recurrence of HR‐NMIBC (HG Ta, any T1 or CIS), progression, or death due to any cause, whichever occurs first. Recurrence or progression of DFS events will be determined by central disease assessments of urine cytology, bladder biopsy, or imaging, as applicable. INCLUSION CRITERIA: 1. 18 or more years of age at the time of informed consent. 2. Histologically confirmed diagnosis by local pathology (within 90 days of documented informed consent) of recurrent, papillary‐only high‐risk non‐muscle‐invasive bladder cancer (HR‐NMIBC; defined as high‐grade [HG] Ta or any T1; no carcinoma in situ [CIS]). 3. Participants with variant histologic subtypes are allowed if tumour(s) demonstrate urothelial (transitional cell histology) predominance. However, neuroendocrine and small cell variants will be excluded. 4. All visible tumour completely resected prior to randomisation. Urine cytology must not be positive or suspicious for HG urothelial carcinoma (UC) before randomisation. For participants with lamina propria invasion (T1) on the Screening biopsy/ transurethral resection of bladder tumour (TURBT), muscularis propria must be present to rule out muscle‐invasive bladder cancer (MIBC). 5. Participants must have received at least 5 of 6 induct SECONDARY OUTCOME: 1. Recurrence‐Free Survival (RFS): The time from randomisation to the first recurrence of HR‐NMIBC, or death due to any cause, whichever occurs first.; 2. Time to Next Intervention (TTNI): The time from randomisation to the time of the next intervention for the treatment of bladder cancer.; 3. Time to Disease Worsening (TTDW): The time from randomisation to cystectomy, systemic therapy, or radiation therapy; 4. Time to Progression (TTP): The time from randomisation to the time of first documented evidence of disease progression, or death due to disease progression, whichever occurs first.; 5. Overall Survival (OS): The time from randomisation to death, due to any cause.; 6. Disease‐free survival (DFS) rate at 12 and 24 months: Percentage of participants with DFS at 12/24 months.; 7. Number of participants with adverse events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE) from the time the participant signs the consent form through to 30 days after the last treatment; 8. Number of participants with change from baseline in laboratory abnormalities at 12, 24, 36, 48, 60, 72, 84, 96, End of Treatment visit, 30‐day safety follow‐up visit; 9. Number of participants with change from baseline in vital signs abnormalities at 12, 24, 36, 48, 60, 72, 84, 96, End of Treatment visit, 30 day safety follow‐up visit; 10. Change from baseline in quality of life measured using the European Organisation for Research and Treatment of Cancer Quality‐of‐life Questionnaire (EORTC QLQ) ‐ C30 scores at [timepoints] 9, 12, 24, 36, 48 and 96 weeks during treatment, End of Treatment and during post‐treatment follow‐up; 11. Change from baseline in quality of life measured using the EORTC QLQ‐ Non‐Muscle‐Invasive Bladder Cancer (NMIBC) 24 scores at 9, 12, 24, 36, 48 and 96 weeks during treatment, End of Treatment and during post‐treatment follow‐up; 12. Proportion of participants with meaningful change in quality of life measured using the EORTC QLQ‐C30 and EORTC QLQ‐NMIBC24 scores at 9, 12, 24, 36, 48 and 96 weeks during treatment, End of Treatment and during post‐treatment follow‐up