A Phase 3 Study of UGN-103 for Treatment of Patients With Low-grade Intermediate-risk Non-muscle Invasive Bladder Cancer

A Phase 3, Single-arm, Multicenter Study to Evaluate the Efficacy and Safety of UGN-103, a Novel Formulation of UGN-102, for the Treatment of Patients With Low-grade (LG) Non-muscle Invasive Bladder Cancer (NMIBC) at Intermediate-risk (IR) of Recurrence

This Phase 3, single-arm, multicenter study will evaluate the efficacy and safety of UGN-103, a novel formulation of UGN-102, instilled in the urinary bladder of patients with low-grade non-muscle invasive bladder cancer (LG-NMIBC).

Eligible patients will be treated with UGN-103 once weekly for 6 weeks (a total of 6 doses).

Efficacy will be assessed by the complete response rate (CRR) at the 3-month Visit (approximately 3 months after the first instillation). Response will be determined based on visual observation (white light cystoscopy), histopathology of any remaining or new lesions by central pathology lab (if applicable), and interpretation of urine cytology by central pathology lab.

Patients who have a complete response (CR) at the 3-month Visit, defined as having no detectable disease (NDD) in the bladder, will enter the Follow-up Period of the study. During the Follow-up Period, patients will return to the clinic every 3 months for evaluation of response. Patients will remain on study until disease recurrence, disease progression, death, or the last patient completes 12 months of follow-up (ie, 12 months after the 3-month Visit), whichever occurs first.

Patients who have a non-complete response (NCR) at the 3-month Visit will undergo investigator designated standard of care (SOC) and have a separate End of Study (EOS) Visit performed.

Inclusion Criteria:

1. Provide written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and the protocol.

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

3. History of at least 1 prior episode of NMIBC. Note: This refers to a previous episode(s) and not to the current episode for which the patient is being screened.

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

   • Presence of multiple tumors.
   • Solitary tumor > 3 cm.
   • Early or frequent recurrence (≥ 1 occurrence of LG-NMIBC within 1 year of the current diagnosis at the initial Screening Visit).

5. Negative voiding cytology for high-grade (HG) disease within 8 weeks before Screening.

6. Has adequate organ and bone marrow function as determined by routine laboratory tests:

   • Leukocytes ≥ 3,000/μL.
   • Absolute neutrophil count ≥ 1,500/μL.
   • Platelets ≥ 100,000/μL.
   • Hemoglobin ≥ 9.0 g/dL.
   • Total bilirubin ≤ 1.5 × 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.

7. Has an anticipated life expectancy of at least the duration of the trial.

8. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 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. Received Bacillus Calmette-Guérin (BCG) treatment for urothelial carcinoma (UC) within the previous 1 year.

2. History of HG bladder cancer (papillary or carcinoma in situ) in the past 2 years.

3. Known allergy or sensitivity to any component of the study treatment (including excipients) that in the investigator's opinion cannot be readily managed.

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

5. History of:

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

6. Past or current muscle invasive bladder cancer (ie, T2, T3, T4) or metastatic UC.

7. Current tumor stage of T1.

8. Concurrent upper tract urothelial carcinoma (UTUC).

9. Evidence of active urinary tract infection (UTI) that in the investigator's opinion cannot be treated and resolved prior to biopsy and/or administration of study treatment.

10. Is pregnant or breastfeeding.

11. 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.

12. History of prior treatment with an intravesical chemotherapeutic agent in the past 2 years except for a single dose of chemotherapy immediately after any previous transurethral resection of bladder tumors (TURBT).

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

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

15. Has any other active malignancy requiring treatment with systemic anticancer therapy (eg, chemotherapy, immunotherapy, radiation therapy). Superficial cancers such as cutaneous basal cell or squamous cell carcinomas that can be treated locally are allowed.

16. Has any other clinically significant medical or surgical condition that in the investigator's opinion could compromise patient safety or the interpretation of study results.

17. Where applicable per country regulation, the patient must not be currently committed to an institution by virtue of an order issued by either judicial or administrative authorities.