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

Phase 3

Active, not recruiting

• Conditions: Bladder Cancer; Urothelial Carcinoma Bladder; Urothelial Carcinoma
• Interventions: Drug: UGN-102

• Registration Number: NCT05243550
• Lead Sponsor: UroGen Pharma Ltd.

Brief Summary

This Phase 3, multinational, single-arm study was designed to evaluate the efficacy and safety of UGN-102 as primary chemoablative therapy in patients with recurrent low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC).

Detailed Description

Eligible patients received 6 once-weekly intravesical instillations of UGN-102.

All patients returned to the clinic approximately 3 months after the first instillation for determination of response to treatment. Assessment of response was 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 had a complete response (CR) at the 3-month Visit, defined as having no detectable disease in the bladder, entered the Follow-up Period of the study. Patients who had a non-complete response (NCR) due to residual LG disease underwent investigator-designated standard of care (SOC) treatment of remaining lesions and then entered the Follow-up Period of the study.

During the Follow-up Period, patients 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 be followed 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 who had a disease recurrence during the Follow-up Period or a disease progression at any time underwent investigator-designated SOC treatment and had a separate End of Study (EOS) Visit performed. The timing of the EOS Visit was approximately 3 months after SOC treatment of disease recurrence or progression.

Study conduct is ongoing and data are summarized through a cutoff date of 04 Apr 2024. As of the data cutoff date, ongoing patients were followed through at least Study Month 15, with the earliest enrolled patients followed through Study Month 21.

Study Timeline

• Study First Submitted: 2022-02-07
• Study First Submitted QC: 2022-02-07
• Study First Posted: 2022-02-17
• Study Start: 2022-03-01
• Primary Completion: 2023-04-26
• Status Verified: 2024-10
• Results First Submitted: 2024-10-04
• Results First Submitted QC: 2024-10-30
• Last Update Submitted: 2024-10-30
• Results First Posted: 2024-11-04
• Last Update Posted: 2024-11-04
• Study Completion: 2028-02

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

1. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form 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 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.

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 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 and alanine aminotransferase ≤ 2.5 × ULN;
   • Alkaline phosphatase ≤ 2.5 × ULN;
   • Estimated glomerular filtration rate ≥ 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 treatment for urothelial carcinoma (UC) within 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 mitomycin 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 grading of T1.

8. Concurrent upper tract UC.

9. Evidence of active urinary tract infection 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 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
UGN-102	UGN-102	Patients will receive 6 once-weekly intravesical instillations of UGN-102 (75 mg mitomycin).

Primary Outcome Measures

Name	Time	Method
Complete Response Rate (CRR)	3 months	CRR is defined as the percentage of patients who achieved a complete response (CR) at the 3-month Visit. A patient was considered a CR if there was no detectable disease in the bladder based on visual observation (white light cystoscopy), biopsy of remaining lesions (if applicable), and voiding urine cytology.

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DOR) in Patients Who Achieved CR at the 3-month Visit	Up to 60 months	DOR is defined as the time from the first documented CR 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.
Durable Complete Response (DCR) Rate in Patients Who Achieved CR at the 3-month Visit	Up to 60 months	DCR rate at scheduled disease assessment time points is defined as the percentage of patients who had a CR at the 3-month Visit and maintained CR up to that particular follow-up visit.
Disease-free Survival (DFS) in Patients Who Achieved CR at the 3-month Visit	Up to 63 months	DFS is defined as the time from the first instillation 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest	Up to 21 months	The number of patients with each type of event is summarized. TEAEs were defined as adverse events (AEs) that started on or after the day of the first instillation of UGN-102 or pre-treatment AEs that worsened during the study.
Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values	6 months	The number of patients with each type of event is summarized.
Number of Participants With Post-baseline PCS Chemistry Values	6 months	The number of patients with each type of event is summarized.

Trial Locations

Locations (65)

Medical University Vienna, Department of Urology; 🇦🇹 Vienna, Austria

Hospital de Basurto; 🇪🇸 Bilbao, Spain

Hospital del Mar; 🇪🇸 Barcelona, Spain

La Paz University Hospital; 🇪🇸 Madrid, Spain

University Hospital Foundation Jimenez Diaz; 🇪🇸 Madrid, Spain

NYU Langone Health; 🇺🇸 New York, New York, United States

University Multiprofile Hospital for Active Treatment "Sveta Marina" - Pleven, Department of Urology; 🇧🇬 Pleven, Bulgaria

Urology Associates, P.C.; 🇺🇸 Nashville, Tennessee, United States

University Multiprofile Hospital for Active Treatment 'Kanev', Ruse, Department of Urology; 🇧🇬 Ruse, Bulgaria

Multiprofile Hospital for Active Treatment - Targovishte; 🇧🇬 Targovishte, Bulgaria

Chesapeake Urology Research Associates; 🇺🇸 Hanover, Maryland, United States

Multiprofile Hospital for Active Treatment "Dr. Tota Venkova", Gabrovo, Department of Urology; 🇧🇬 Gabrovo, Bulgaria

North Estonia Medical Centre Foundation Ltd., Surgery Clinic, General and Oncology Urology Centre; 🇪🇪 Tallinn, Estonia

Clinical Hospital Center Zemun, Urology unit; 🇷🇸 Belgrade, Serbia

Atlantic Health System; 🇺🇸 Morristown, New Jersey, United States

John Hopkins University; 🇺🇸 Baltimore, Maryland, United States

University Multiprofile Hospital for Active Treatment, Plovdiv; 🇧🇬 Plovdiv, Bulgaria

University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Urology Clinic; 🇧🇬 Sofia, Bulgaria

Multiprofile Hospital for Active Treatment "Sveti Pantaleymon", Yambol, Department of Urology; 🇧🇬 Yambol, Bulgaria

Multiprofile Hospital for Active Treatment "Sveta Anna", Varna, Urology Clinic; 🇧🇬 Varna, Bulgaria

Multiprofile Hospital for Active Treatment - Blagoevgrad; 🇧🇬 Blagoevgrad, Bulgaria

University Multiprofile Hospital for Active Treatment "Tsaritsa Yoanna - ISUL", Sofia; 🇧🇬 Sofia, Bulgaria

SCM sp. z o.o. (LLC); 🇵🇱 Kraków, Poland

Clinical Hospital Center Bezanijska Kosa, Clinic of Surgery, Department of Urology; 🇷🇸 Belgrade, Serbia

Clinical Center Kragujevac, Clinic of Urology, Nephrology and Dialysis; 🇷🇸 Kragujevac, Serbia

Multiprofile Hospital for Active Treatment "Life Hospital" Burgas; 🇧🇬 Varna, Bulgaria

University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv; 🇧🇬 Plovdiv, Bulgaria

Multiprofile Hospital for Active Treatment Park Hospital; 🇧🇬 Plovdiv, Bulgaria

Multiprofile Hospital for Active Treatment - Shumen, Shumen, Department of Urology; 🇧🇬 Shumen, Bulgaria

Tartu University Hospital, Surgery Clinic, Department of Urology and Kidney Transplantation; 🇪🇪 Tartu, Estonia

LTD Central University Clinic After Academic N. Kipshidze; 🇬🇪 Tbilisi, Georgia

JSC Jerarsi, Department of Urology; 🇬🇪 Tbilisi, Georgia

LTD Gidmedi, Urology Department; 🇬🇪 Tbilisi, Georgia

Vilnius University Hospital Santaros Klinikos; 🇱🇹 Vilnius, Lithuania

Tbilisi State Medical University and Ingorokva High Technology Medical Center University Clinic LTD, Urology Department; 🇬🇪 Tbilisi, Georgia

Clinical Research Center Limited liability company Medic-R Limited partnership; 🇵🇱 Poznań, Poland

Clinical Center of Serbia, Clinic of Urology; 🇷🇸 Belgrade, Serbia

LLC Riga East University Hospital, Clinic of Urology and Oncologic Urology; 🇱🇻 Riga, Latvia

Daugavpils Regional Hospital, Urology Department; 🇱🇻 Riga, Latvia

Hospital of Lithuanian University of Health Sciences Kauno Klinikos; 🇱🇹 Kaunas, Lithuania

Klaipeda University Hospital; 🇱🇹 Klaipėda, Lithuania

Arizona Urology Specialists; 🇺🇸 Tucson, Arizona, United States

Wichita Urology Group; 🇺🇸 Wichita, Kansas, United States

Spokane Urology, P.S.; 🇺🇸 Spokane, Washington, United States

Multiprofile Hospital for Active Treatment "Sveti Nikolai Chudotvorets", Lom; 🇧🇬 Lom, Bulgaria

University Hospital 12 de Octubre; 🇪🇸 Madrid, Spain

Loma Linda University Medical Center; 🇺🇸 Loma Linda, California, United States

Genesis Research; 🇺🇸 San Diego, California, United States

University of Missouri; 🇺🇸 Columbia, Missouri, United States

Great Lakes Physician dba WNY Urology Associates; 🇺🇸 Cheektowaga, New York, United States

AccuMed Research Associates; 🇺🇸 Garden City, New York, United States

Manhattan Medical Research; 🇺🇸 New York, New York, United States

Mount Sinai; 🇺🇸 New York, New York, United States

Houston Methodist Research Institute; 🇺🇸 Houston, Texas, United States

Multiprofile Hospital for Active Treatment "City Clinic - Sveti Georgi"; 🇧🇬 Montana, Bulgaria

University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski", Pleven, Urology Clinic; 🇧🇬 Pleven, Bulgaria

Multiprofile Hospital for Active Treatment, Varna part of Military Medical Academy, Clinic of Urology; 🇧🇬 Varna, Bulgaria

East Viru Central Hospital, Surgery Clinic; 🇪🇪 Kohtla-Järve, Estonia

East Tallinn Central Hospital Ltd., Surgery Clinic, Centre of Urology; 🇪🇪 Tallinn, Estonia

West Tallinn Central Hospital Ltd., Department of Urology; 🇪🇪 Tallinn, Estonia

Pineo Medical Ecosystem Ltd., Department of Urology; 🇬🇪 Tbilisi, Georgia

P. Stradins Clinical University Hospital, Center for Urology; 🇱🇻 Riga, Latvia

Liepajas Regional Hospital, Urology Department; 🇱🇻 Liepāja, Latvia

AKMED; 🇵🇱 Gliwice, Poland

Mazovian Oncology Hospital, Subdepartment of Urology; 🇵🇱 Wieliszew, Poland