A Phase 3 Single-arm Study of UGN-103 for the Treatment of LG IR NMIBC.

Phase 3

Active, not recruiting

• Conditions: Nonmuscle Invasive Bladder Cancer
• Interventions: Drug: UGN-103

• Registration Number: 2023-507261-25-00
• Lead Sponsor: Urogen Pharma Ltd.

Brief Summary

To evaluate the tumor ablative effect of UGN-103, a novel formulation of UGN-102, in patients with LG NMIBC.

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 Timeline

• Study First Posted: 2024-08-14
• Last Update Posted: 2025-04-23

Recruitment & Eligibility

• Status: Ongoing, recruitment ended
• Sex: Not specified
• Target Recruitment: 57

Inclusion Criteria

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

2. Patient must be ≥ 18 years of age at the time of informed consent.

3. Patient who has LG NMIBC (Ta) histologically confirmed by cold cup biopsy at Screening or within 8 weeks before Screening. Note: This is a diagnostic biopsy to demonstrate histopathology of tumor and resection of the tumor is not to be performed. Residual tumor must be present and documented after biopsy and before instillation of study treatment.

4. 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.

5. Has intermediate risk disease, defined as having 1 or 2 of the following: a. Presence of multiple tumors. b. Solitary tumor > 3 cm. c. Early or frequent recurrence (≥ 1 occurrence of LG NMIBC within 1 year of the current diagnosis at the initial Screening Visit) Note: Patients with all 3 factors are considered high risk and are not eligible to participate.

6. Negative voiding cytology for HG disease within 8 weeks before Screening

7. Has adequate organ and bone marrow function as determined by routine laboratory tests as below: • Leukocytes ≥ 3,000/μL (≥ 3 × 109/L). • Absolute neutrophil count ≥ 1,500/μL (≥ 1.5 × 109/L). • Platelets ≥ 100,000/μL (≥ 100 × 109/L). • Hemoglobin ≥ 9.0 g/dL. • Total bilirubin ≤ 1.5 × ULN. • AST and ALT ≤ 2.5 × ULN. • ALP ≤ 2.5 × ULN. • eGFR ≥ 30 mL/min.

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

9. Both male and female patients: Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Female partner of male patient: Willing to use 2 acceptable forms of effective contraception from enrollment through 6 months post treatment if the female partner is of childbearing potential (defined as premenopausal women who have not been sterilized). Acceptable methods of birth control which are considered to have a low failure rate (ie, less than 1% per year) when used consistently and correctly, such as 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, postovulation methods) is NOT an acceptable method of contraception. b. Female patient: Willing to use 2 acceptable forms of effective contraception from enrollment through 6 months post treatment if the patient is of childbearing potential (defined as premenopausal women who have not been sterilized)

Exclusion Criteria

1. Received BCG treatment for UC within the previous 1 year.

2. Is pregnant or breastfeeding

3. 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

4. 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

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

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

7. 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.

8. 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

9. 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

10. History of HG bladder cancer (papillary or CIS) in the past 2 years

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

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

13. History of: a. Neurogenic bladder. b. Active urinary retention. c. Any other condition that would prohibit normal voiding

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

15. Current tumor staging of T1

16. Concurrent UTUC

17. Evidence of active UTI that in the investigator’s opinion cannot be treated and resolved prior to biopsy and/or administration of study treatment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
UGN-103	UGN-103	Patients will receive UGN-103 (75 mg mitomycin) once weekly for 6 weeks (a total of 6 doses).

Primary Outcome Measures

Name	Time	Method
CRR, defined as the proportion of patients who achieved CR at the 3-month Visit (3 months after the first instillation of UGN-103) as determined by cystoscopy, for cause biopsy, and urine cytology.		CRR, defined as the proportion of patients who achieved CR at the 3-month Visit (3 months after the first instillation of UGN-103) as determined by cystoscopy, for cause biopsy, and urine cytology.

Secondary Outcome Measures

Name	Time	Method
1. DOR in patients who achieved CR at the 3-m Visit, defined as the time from the date of evidence of CR at the 3-m Visit to the earliest date of recurrence or progression as determined using the date of cystoscopy, for cause biopsy, or cytology, or death due to any cause, whichever occurred first.		1. DOR in patients who achieved CR at the 3-m Visit, defined as the time from the date of evidence of CR at the 3-m Visit to the earliest date of recurrence or progression as determined using the date of cystoscopy, for cause biopsy, or cytology, or death due to any cause, whichever occurred first.
2. Safety and tolerability will be evaluated through the reporting of AEs, including SAEs and AESIs, and through standard clinical and l laboratory tests (eg, hematology and chemistry, urinalysis, physical examination, and vital signs)		2. Safety and tolerability will be evaluated through the reporting of AEs, including SAEs and AESIs, and through standard clinical and l laboratory tests (eg, hematology and chemistry, urinalysis, physical examination, and vital signs)
3. Concentration data and PK parameters (Cmax, tmax, and AUC		3. Concentration data and PK parameters (Cmax, tmax, and AUC
Exploratory 1. Changes from baseline in patient scores on the QLQ-C30 and TSQM questionnaires		Exploratory 1. Changes from baseline in patient scores on the QLQ-C30 and TSQM questionnaires
Exploratory 2. DNA, RNA and/or protein biomarkers in tumor tissue		Exploratory 2. DNA, RNA and/or protein biomarkers in tumor tissue
Exploratory 3. Number (%) of response outcomes evaluated at the first disease assessment visit after SoC		Exploratory 3. Number (%) of response outcomes evaluated at the first disease assessment visit after SoC

Trial Locations

Locations (27)

University Multiprofessional Hospital For Active Treatment Plovdiv AD; 🇧🇬 Plovdiv, Bulgaria

Multiprofile Hospital For Active Treatment Dr. Tota Venkova AD; 🇧🇬 Gabrovo, Bulgaria

University Multiprofile Hospital For Active Treatment And Emergency Medicine N I Pirogov; 🇧🇬 Sofiya, Bulgaria

Multiprofile Hospital For Active Treatment - Shumen AD; 🇧🇬 Shumen, Bulgaria

University Multiprofile Hospital For Active Treatment Saint Georgi EAD; 🇧🇬 Plovdiv, Bulgaria

University Multiprofessional Hospital For Active Treatment Kanev AD; 🇧🇬 Ruse, Bulgaria

University Multiprofile Hospital For Active Treatment Dr. Georgi Stranski EAD; 🇧🇬 Pleven, Bulgaria

MBAL Varna EOOD; 🇧🇬 Varna, Bulgaria

Sihtasutus Ida-Viru Keskhaigla; 🇪🇪 Kohtla-Jarve Linn, Estonia

North Estonia Medical Centre Foundation; 🇪🇪 Tallinn, Estonia

Scroll for more (17 remaining)

University Multiprofessional Hospital For Active Treatment Plovdiv AD

🇧🇬Plovdiv, Bulgaria

Dimitar Shishkov

Site contact

+359876204556

drshishkov@abv.bg