A Study to Evaluate TAR-210 Versus Intravesical Chemotherapy Treatment in Participants With High Risk Non-Muscle-Invasive Bladder Cancer (MoonRISe-3)

Janssen (J&J Innovative Medicine)

Status and phase: Begins enrollment in 2 months; Phase 3

Conditions: Non-Muscle Invasive Bladder Neoplasms

Treatments: Drug: Mitomycin C; Drug: Gemcitabine; Drug: TAR-210

Study type: Interventional

Funder types: Industry

Identifiers

NCT06919965

42756493BLC3005 (Other Identifier)

2024-519493-39-00 (Registry Identifier)

Details and patient eligibility

About

The main purpose of this study is to compare the disease-free survival (the length of time after randomization that a participant survives without any signs or symptoms of the cancer returning, or progressing) between Bacillus Calmette-Guérin (BCG) treated participants receiving treatment with TAR-210 versus investigator's choice of intravesical chemotherapy for treatment of high-risk non-muscle-invasive bladder cancer (HR-NMIBC).

Enrollment: 220 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed diagnosis by local pathology of papillary-only HR-NMIBC (defined as high-grade Ta or any T1, no CIS). Mixed histology tumors are allowed if urothelial differentiation is predominant. However, neuroendocrine, and small cell variants will be excluded
• Have a susceptible fibroblast growth factor receptor (FGFR) mutation or fusion either by urine testing or tumor tissue testing (from TURBT tissue) as determined by central or local testing
• All visible tumor completely resected prior to randomization. Urine cytology must not be positive or suspicious for high grade UC before randomization. For participants with lamina propria invasion (T1) on the screening biopsy/TURBT, muscularis propria must be present to rule out MIBC
• Participants must have had either: a. Adequate Induction (5 of 6 doses) and either 2 of 3 doses of Maintenance or 2 of 6 doses of second Induction of BCG with high-grade T1 disease at first disease assessment after induction or high-grade Ta/any T1 disease within 6 months after last BCG (BCG-unresponsive population); b. had adequate induction (5 or 6 doses) with or without maintenance BCG with high-grade Ta/any T1 disease within 12 months after last BCG excluding BCG-unresponsive (BCG-experienced population); or c. been unable to complete an induction course of BCG with at least 5 doses due to grade >= 2 toxicity requiring BCG discontinuation (BCG intolerant population)
• Have an Eastern Cooperative Oncology Group (ECOG) performance status Grade of 0, 1, or 2
• Must be ineligible for or refusing radical cystectomy (RC)

Exclusion criteria

• Presence of CIS at any point from time of diagnosis of papillary-only HR-NMIBC recurrence to randomization. Additionally, presence or history of histologically confirmed, muscle-invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (that is [i.e.], T2, T3, T4, N+, and/or M+)
• Active malignancies (i.e., progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. Allowed recent second or prior malignancies: a. Any malignancy that was not progressing nor requiring treatment change in the last 12 months; b. Malignancies treated within the last 12 months and considered at very low risk for recurrence for example (e.g.): non-melanoma skin cancers (treated with curative therapy or localized melanoma treated with curative surgical resection alone), non-invasive cervical cancer, breast cancer (adequately treated lobular CIS or ductal CIS, localized breast cancer and receiving antihormonal agents), localized prostate cancer ([N0, M0] with a Gleason score less than or equal to [<=] 7a, treated locally only [radical prostatectomy/radiation therapy/focal treatment]) and other malignancy that is considered at minimal risk of recurrence
• 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 210
• A history of clinically significant polyuria with recorded 24 hour urine volumes greater than (>) 4,000 milliliters (mL)
• Indwelling catheters are not permitted; however, intermittent catheterization is acceptable

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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220 participants in 2 patient groups

Group A: TAR-210

Experimental group

Description:

Participants in Group A will have TAR-210 inserted in the bladder on Day 1. TAR-210 will be inserted over a treatment duration of approximately 2 years.

Treatment:

Drug: TAR-210

Group B: Mitomycin C (MMC) or Gemcitabine

Active Comparator group

Description:

Participants in Group B will receive intravesical mitomycin C (MMC) or gemcitabine (investigator's choice) once weekly for 4 to 6 induction doses followed by maintenance dosing once monthly for up to 1 year. An optional second year of additional maintenance can be added at the investigator's discretion.

Treatment:

Drug: Gemcitabine

Drug: Mitomycin C