A Phase 3 Single-arm Study of UGN-104 for the Treatment of Low-grade Upper Tract Urothelial Cancer

Inclusion Criteria

• •1. Provide written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and protocol.
• •2. Naive or recurrent patients with LG, non-invasive UTUC in the pyelocalyceal system, with the following disease characteristics:
• •1. At least 1 measurable papillary LG tumor, evaluated visually, ≤ 15 mm. The largest lesion should not exceed 15 mm. Debulking to ≤ 15 mm is permitted.
• •2. Biopsy taken from at least 1 tumor located above the ureteropelvic junction revealing LG urothelial carcinoma (UC). Patients who have been biopsied within 8 weeks before Screening for this study and shown to have LG UC may have these historical biopsies used for enrollment into the study and do not require repeat biopsy during Screening.
• •3. Patient should have at least 1 remaining papillary LG tumor evaluated visually with a diameter of at least 5 mm post-biopsy.
• •4. Wash urine cytology sampled from the pyelocalyceal system documenting the absence of high-grade (HG) UC, diagnosed not more than 8 weeks before Screening.
• •3. Patients with Eastern Cooperative Oncology Group (ECOG) performance status \< 3 (with Karnofsky \> 40).
• •4. Patients with life expectancy \> 24 months at time of Screening.
• •5. Patients must have adequate organ and bone marrow function as determined by the following routine laboratory tests:
• •1. Leukocytes ≥ 3,000/μL (≥ 3 × 10\^9/L).
• •2. Absolute neutrophil count ≥ 1,500/μL (≥ 1.5 × 10\^9/L).
• •3. Platelets ≥ 100,000/μL (≥ 100 × 10\^9/L).
• •4. Hemoglobin ≥ 9.0 g/dL.
• •5. Total bilirubin ≤ 1.5 × upper limit of normal (ULN).
• •6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN.
• •7. Alkaline phosphatase ≤ 2.5 × ULN.
• •8. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min.
• •6. Patient has no active urinary tract infection (UTI) as confirmed by urine culture or urinalysis. Note: In case of a symptomatic UTI the patient will be treated with antibiotics and the instillation will be postponed until resolution. In the case of asymptomatic bacteriuria, the use of prophylactic antibiotics and postponement of treatment is at the discretion of the investigator.
• •7. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for clinical study participants.
• •Female patients of childbearing potential (defined as premenopausal women who have not been sterilized) and male patients with female partners of childbearing potential must agree to use 2 acceptable forms of effective contraception from enrollment through 6 months post treatment. Sexually active male patients must agree to use a condom during intercourse for at least 48 hours after each instillation.
• •Acceptable methods of birth control considered to have a low failure rate (ie, less than 1% per year) when used consistently and correctly include implants, injectable, combined (estrogen/progesterone) oral contraceptives, intrauterine devices (only hormonal), condoms with spermicide, sexual abstinence\* or vasectomized partner.
• •\* Sexual abstinence is defined as refraining from intercourse from enrollment through 6 months post treatment. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is NOT an acceptable method of contraception.