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

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Bladder Cancer; Urothelial Carcinoma Bladder; Urothelial Carcinoma
• Intervention / Treatment: Drug: UGN-103

Detailed Description

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, 15 months after the first instillation), 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.

• Study Type: Interventional
• Enrollment (Estimated): 87
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Karrie Hilsinger; Phone Number: +1 609-256-8316; Email: karrie.hilsinger@urogen.com
• Study Contact Backup: Name: Renee Sumlin; Phone Number: +1 346-573-2671; Email: renee.sumlin@urogen.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: UGN-103; Patients will receive UGN-103 once weekly for 6 weeks (a total of 6 doses).

Drug: UGN-103; UGN-103 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-103 allow for local administration of mitomycin as a liquid under chilled conditions, with subsequent conversion to a semi-solid gel depot following instillation into the bladder. The UGN-103 admixture for intravesical instillations contains 75 mg mitomycin in 56 mL admixture (1.33 mg mitomycin per 1 mL).; Other Names: UGN-103 (mitomycin) for intravesical solution

What is the study measuring?

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 21 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 21 months
Incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of special interest, and abnormal clinical laboratory test results (hematology and serum chemistry)	The number of patients with each type of event will be summarized.	Up to 21 months
Mitomycin plasma concentrations	Mitomycin plasma concentrations will be assessed in a subset of patients treated with UGN-103	0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-103.
Mitomycin maximum plasma concentration (Cmax)	Mitomycin Cmax will be assessed in a subset of patients treated with UGN-103	0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-103.

Collaborators and Investigators

• Sponsor: UroGen Pharma Ltd.
• Investigators: Study Director: Sunil Raju, MBBS, UroGen Pharma

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: NMIBC; Non-muscle invasive bladder cancer; Mitomycin; UGN-102; Low-grade non-muscle invasive bladder cancer; Intermediate-risk non-muscle invasive bladder cancer; UGN-103
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Non-Muscle Invasive Bladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Alkylating Agents; Antibiotics, Antineoplastic; Mitomycins; Mitomycin
• Other Study ID Numbers: BL013

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No