A Phase 2b Study of UGN-102 for Low Grade Intermediate Risk Non-Muscle-Invasive Bladder Cancer

This Phase 2b, single-arm, multicenter study evaluated the efficacy and safety of UGN-102 as primary chemoablative therapy in patients with low grade intermediate risk non-muscle-invasive bladder cancer (LG IR NMIBC).

Eligible patients were treated with 6 once-weekly intravesical instillations of UGN-102.

The ablative effect of UGN-102 was evaluated at the 3-month Visit, which occurred 5 weeks ± 1 week after the last weekly instillation (3 months after initiation of study drug). Response was determined based on visual evaluation by cystoscopy (appearance, number, and size of the lesions) and, if there were remaining lesions, by histopathology of the remaining lesions. Complete response (CR) was defined as having no detectable disease (NDD) and was assessed visually during cystoscopy and also by urine cytology. In the event that the investigator was not sure, and there was suspect tissue, a small biopsy was taken from the suspect tissue to confirm CR in addition to cystoscopy and urine cytology.

Patients who achieved a CR continued to have monthly telephone contacts to document any adverse events (AEs) and changes in concomitant medications and were assessed at 6, 9, and 12 months after the first instillation of UGN-102 for evidence of disease recurrence. Patients who had a non-complete response (non-CR) discontinued the study and continued with standard of care according to their treating physician.

Safety was determined based on a review of AEs, laboratory assessments, and physical examination findings.

Eligibility Criteria:
Inclusion Criteria:

1. Willing and able to sign an informed consent and comply with the protocol.
2. Has newly diagnosed or historic LG NMIBC (Ta) histologically confirmed by cold cup biopsy at screening or within 6 weeks of screening.
3. Is at intermediate risk of recurrence, 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. Has negative voiding cytology for high grade (HG) disease at or within 6 weeks of enrollment.
5. Willing to use 2 acceptable forms of effective contraception from enrollment through 6 months post treatment if the participant is female or the female partner of a male participant and is of childbearing potential (defined as premenopausal women who have not been sterilized).
6. Has adequate organ and bone marrow function as determined by routine laboratory tests as below:

   * Leukocytes ≥ 3,000 per μL;
   * Absolute neutrophil count ≥ 1,500 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 ≤ 2.5 × ULN;
   * Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min.
7. Has no evidence of active urinary tract infection (UTI) at Screening and Baseline visits.

   * In the case of symptomatic UTI, the patient will be treated with a full course of antibiotics, and study drug will be postponed until resolution. In the case of asymptomatic bacteriuria, the use of prophylactic antibiotics and postponement of study drug is left to the discretion of the Principal Investigator (PI).

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 2 years.
3. History of HG papillary UC in the past 2 years.
4. Known allergy or sensitivity to mitomycin.
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 urothelial carcinoma (UTUC).
9. Has participated in a study with an investigational agent or device within 30 days of enrollment.
10. History of prior treatment with an intravesical chemotherapeutic agent with the exception of a single dose of chemotherapy immediately after any previous transurethral resection of bladder tumors (TURBT).
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.