A Phase 3 Study of UGN-102 for Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer

A Randomized, Controlled, Open-Label Study of the Efficacy, Durability, and Safety of UGN-102 With or Without TURBT in Patients With Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer (LG-IR-NMIBC)

This global, randomized, controlled, open-label Phase 3 study was designed to assess the long-term efficacy and safety of UGN-102 (mitomycin) for intravesical solution with or without (±) transurethral resection of bladder tumors (TURBT) versus TURBT alone for the treatment of patients with low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC).

Eligible patients were randomized in a 1:1 ratio to UGN-102 ± TURBT or TURBT alone. Randomization was stratified by the presence of a previous LG-NMIBC episode within 1 year of the current diagnosis (yes or no). Starting on Day 1, patients randomized to the UGN-102 ± TURBT arm will receive 6 weekly intravesical instillations of UGN-102 and patients randomized to the TURBT alone arm underwent TURBT.

All patients returned to the clinic approximately 3 months after the start of treatment for a disease assessment visit. Response to treatment was determined based on visual observation (white light cystoscopy), histopathology of any remaining or new lesions, and voiding urine cytology. Patients confirmed to have a complete response (CR), defined as having no detectable disease (NDD) in the bladder, received no further treatment and entered the Follow-up Period of the study. Patients confirmed to have a non-complete response (NCR) due to residual LG disease in either treatment arm underwent TURBT of any remaining lesions and then entered the Follow-up Period of the study.

During the Follow-up Period, patients returned to the clinic every 3 months to determine if they remained disease free. Patients remained on study until completion of all follow-up visits or until disease recurrence, disease progression, or death was documented, whichever occurred first. Patients determined to have a protocol-defined recurrence or progression at any follow-up or unscheduled visit were considered to have completed the study and released to the care of their treating physician.

Study enrollment was stopped early by the sponsor to pursue an alternative development strategy for UGN-102 in the treatment of bladder cancer. Patients who had consented at the time the trial terminated were permitted to continue, but follow-up was terminated once the last patient had been followed for 15 months after the start of treatment.

Inclusion Criteria:

1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.

2. Patient who has newly diagnosed or historic LG-NMIBC (Ta) histologically confirmed by cold cup biopsy at Screening or within 8 weeks of Screening.

3. Has intermediate risk disease, defined as having 1 or 2 of the following:

   • Presence of multiple tumors;
   • Solitary tumor > 3 cm;
   • Recurrence (≥ 1 occurrence of LG-NMIBC within 1 year of the current diagnosis).

4. Negative voiding cytology for HG disease within 6 weeks of Screening.

5. Has adequate organ and bone marrow function as determined by the following routine laboratory tests:

   • Leukocytes ≥ 3,000 cells per μL;
   • Absolute neutrophil count ≥ 1,500 cells per μL;
   • Platelets ≥ 100,000 per μL;
   • Hemoglobin ≥ 9.0 g/dL;
   • Total bilirubin ≤ 1.5 x upper limit of normal (ULN);
   • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN;
   • Alkaline phosphatase (ALP) ≤ 2.5 × ULN;
   • Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min.

6. Has no evidence of active urinary tract infection (UTI).

7. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for clinical study participants. Women of childbearing potential (defined as premenopausal women who have not been sterilized), including female patients and female partners of male patients, must be willing to use 2 acceptable forms of effective contraception from enrollment through 6 months post-treatment.

Exclusion Criteria:

1. History of carcinoma in situ (CIS) on preliminary cystoscopy within 5 years of enrollment.

2. Received Bacillus Calmette-Guérin (BCG) treatment for urothelial carcinoma (UC) within previous 1 year.

3. History of HG papillary UC in the past 2 years.

4. Known allergy or sensitivity to mitomycin that in the investigator's opinion cannot be readily managed.

5. Clinically significant urethral stricture that would preclude passage of a urethral catheter.

6. History of pelvic radiotherapy.

7. History of:

   • Neurogenic bladder;
   • Active urinary retention;
   • Any other condition that would prohibit normal voiding.

8. Past or current muscle invasive (ie, T2, T3, T4) or metastatic UC or concurrent upper tract UC.

9. Current tumor stage of T1.

10. Has an underlying substance abuse or psychiatric disorder such that, in the opinion of the investigator, the patient would be unable to comply with the protocol.

11. History of prior treatment with an intravesical chemotherapeutic agent except for a single dose of chemotherapy immediately after any previous TURBT.

12. Has previously participated in a study in which they received UGN-102.

13. Has participated in a study with an investigational agent or device within 30 days of randomization.