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

Study Overview
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Brief Summary
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This Phase 3, multinational, single-arm, multicenter study will evaluate 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).

Detailed Description
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Eligible patients will receive 6 once-weekly intravesical instillations of UGN-102. All patients will return to the clinic approximately 3 months after the first instillation for determination of response to treatment. Assessment of response will be 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 confirmed to 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. Patients confirmed to have a non-complete response (NCR) will undergo Investigator designated standard of care (SOC) treatment of remaining lesions and then enter the Follow-up Period of the study. During the Follow-up Period, patients will return to the clinic every 3 months for up to 24 months (ie, 27 months after the first instillation) for evaluation of response. Patients who remain disease free at the 27-month Visit will continue to return to the clinic every 6 months for up to 36 months (ie, 63 months after the first instillation) or until disease recurrence, disease progression, death, or the study is closed by the Sponsor, whichever occurs first. Patients confirmed to have a disease recurrence during the Follow-up Period or a disease progression at the 3-month Visit or during the Follow-up Period will undergo Investigator designated SOC treatment and have a separate End of Study (EOS) Visit performed. The timing of the EOS Visit will be approximately 3 months after SOC treatment of disease recurrence or progression.

Official Title
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A Phase 3, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of UGN-102 as Primary Chemoablative Therapy in Patients With Low Grade (LG) Non-Muscle-Invasive Bladder Cancer (NMIBC) at Intermediate Risk (IR) of Recurrence

Conditions
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Bladder Cancer, Urothelial Carcinoma, Urothelial Carcinoma Bladder

Intervention / Treatment
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* Drug: UGN-102


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and the protocol. Patient who has LG NMIBC (Ta) histologically confirmed by cold cup biopsy at Screening or within 8 weeks before Screening. History of LG NMIBC requiring treatment with transurethral resection of bladder tumors (TURBT). Note: This refers to a previous episode(s) and not to the current episode for which the patient is being screened. 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). Negative voiding cytology for high grade (HG) disease within 8 weeks before Screening. 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 (ALP) ≤ 2.5 × ULN; Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min. Has an anticipated life expectancy of at least the duration of the trial. 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: Received Bacillus Calmette-Guérin (BCG) treatment for urothelial carcinoma (UC) within previous 1 year. History of HG bladder cancer (papillary or carcinoma in situ [CIS]) in the past 2 years. Known allergy or sensitivity to mitomycin that in the Investigator's opinion cannot be readily managed. Clinically significant urethral stricture that would preclude passage of a urethral catheter. History of: Neurogenic bladder; Active urinary retention; Any other condition that would prohibit normal voiding. Past or current muscle invasive bladder cancer (ie, T2, T3, T4) or metastatic UC. Current tumor grading of T1. Concurrent upper tract urothelial carcinoma (UTUC). 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. Is pregnant or breastfeeding. 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. 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 TURBT. Has participated in a study with an investigational agent or device within 30 days of enrollment. Has previously participated in a study in which they received UGN-102. 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UGN-102<br>Patients will receive 6 once-weekly intravesical instillations of UGN-102. | Drug: UGN-102<br>* UGN-102 consists of mitomycin and sterile hydrogel (a proprietary thermally responsive gel) that is used to reconstitute mitomycin before instillation. The reverse thermal properties of UGN-102 allow for local administration of mitomycin as a liquid, with subsequent conversion to a semi-solid gel depot following instillation into the bladder. The UGN-102 admixture for intravesical instillations contains 75 mg mitomycin in 56 mL admixture (1.33 mg mitomycin per 1 mL).<br>* Other names: UGN-102 (mitomycin) for intravesical solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate (CRR) | CRR is defined as the proportion of patients who achieved CR at the 3-month Visit. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response (DOR) | DOR is defined as the time from the date of evidence of CR at the 3-month Visit to the earliest date of recurrence or progression or death due to any cause, whichever occurred first. | Up to 63 months | 
| Durable complete response (DCR) rate | DCR rate at scheduled disease assessment time points, defined as the proportion of patients who achieved CR at the 3-month Visit and maintained CR (ie, no detectable disease) up to that particular follow-up disease assessment. | Up to 63 months | 
| Disease-free survival (DFS) | DFS in patients who achieved CR at the 3-month Visit, defined as the time from first dose to the earliest date of recurrence or progression or death due to any cause, whichever occurred first. | Up to 63 months | 
| Incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of special interest, and abnormal clinical laboratory test results (hematology, serum chemistry, and urinalysis). | The number of patients with each type of event will be summarized. | Up to 63 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-muscle invasive bladder cancer, Low grade non-muscle invasive bladder cancer, Intermediate risk non-muscle invasive bladder cancer, NMIBC, UGN-102, Mitomycin