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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Bladder Cancer; Urothelial Carcinoma Bladder; Urothelial Carcinoma
• Intervention / Treatment: Drug: UGN-102

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 Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University Vienna, Department of Urology
• Bulgaria
  • Blagoevgrad, Bulgaria, 2700
    • Multiprofile Hospital for Active Treatment - Blagoevgrad
  • Gabrovo, Bulgaria, 5300
    • Multiprofile Hospital for Active Treatment "Dr. Tota Venkova", Gabrovo, Department of Urology
  • Lom, Bulgaria, 3600
    • Multiprofile Hospital for Active Treatment "Sveti Nikolai Chudotvorets", Lom
  • Montana, Bulgaria, 3400
    • Multiprofile Hospital for Active Treatment "City Clinic - Sveti Georgi"
  • Pleven, Bulgaria, 5800
    • University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski", Pleven, Urology Clinic
  • Pleven, Bulgaria, 5800
    • University Multiprofile Hospital for Active Treatment "Sveta Marina" - Pleven, Department of Urology
  • Plovdiv, Bulgaria, 4002
    • University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv
  • Plovdiv, Bulgaria, 4003
    • University Multiprofile Hospital for Active Treatment, Plovdiv
  • Plovdiv, Bulgaria, 4109
    • Multiprofile Hospital for Active Treatment Park Hospital
  • Rousse, Bulgaria, 7000
    • University Multiprofile Hospital for Active Treatment 'Kanev', Ruse, Department of Urology
  • Shumen, Bulgaria, 9700
    • Multiprofile Hospital for Active Treatment - Shumen, Shumen, Department of Urology
  • Sofia, Bulgaria, 1606
    • University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Urology Clinic
  • Sofia, Bulgaria, 1527
    • University Multiprofile Hospital for Active Treatment "Tsaritsa Yoanna - ISUL", Sofia
  • Targovishte, Bulgaria, 7700
    • Multiprofile Hospital for Active Treatment - Targovishte
  • Varna, Bulgaria, 9000
    • Multiprofile Hospital for Active Treatment, Varna part of Military Medical Academy, Clinic of Urology
  • Varna, Bulgaria, 9002
    • Multiprofile Hospital for Active Treatment "Sveta Anna", Varna, Urology Clinic
  • Varna, Bulgaria, 8008
    • Multiprofile Hospital for Active Treatment "Life Hospital" Burgas
  • Yambol, Bulgaria, 8600
    • Multiprofile Hospital for Active Treatment "Sveti Pantaleymon", Yambol, Department of Urology
• Estonia
  • Kohtla-Järve, Estonia, 31025
    • East Viru Central Hospital, Surgery Clinic
  • Tallinn, Estonia, 10138
    • East Tallinn Central Hospital Ltd., Surgery Clinic, Centre of Urology
  • Tallinn, Estonia, 10617
    • West Tallinn Central Hospital Ltd., Department of Urology
  • Tallinn, Estonia, 13419
    • North Estonia Medical Centre Foundation Ltd., Surgery Clinic, General and Oncology Urology Centre
  • Tartu, Estonia, 50406
    • Tartu University Hospital, Surgery Clinic, Department of Urology and Kidney Transplantation
• Georgia
  • Tbilisi, Georgia, 0160
    • LTD Central University Clinic After Academic N. Kipshidze
  • Tbilisi, Georgia
    • JSC Jerarsi, Department of Urology
  • Tbilisi, Georgia
    • LTD Gidmedi, Urology Department
  • Tbilisi, Georgia
    • Pineo Medical Ecosystem Ltd., Department of Urology
  • Tbilisi, Georgia
    • Tbilisi State Medical University and Ingorokva High Technology Medical Center University Clinic LTD, Urology Department
• Latvia
  • Liepāja, Latvia, LV-3414
    • Liepajas Regional Hospital, Urology Department
  • Riga, Latvia, LV-1002
    • P. Stradins Clinical University Hospital, Center for Urology
  • Riga, Latvia, LV-1038
    • LLC Riga East University Hospital, Clinic of Urology and Oncologic Urology
  • Riga, Latvia, LV-5417
    • Daugavpils Regional Hospital, Urology Department
• Lithuania
  • Kaunas, Lithuania, LT-50161
    • Hospital of Lithuanian University of Health Sciences Kauno Klinikos
  • Klaipėda, Lithuania, LT-92288
    • Klaipeda university hospital
  • Vilnius, Lithuania, 08661
    • Vilnius University Hospital Santaros Klinikos
• Poland
  • Gliwice, Poland, 44-100
    • AKMED
  • Krakow, Poland, 31-559
    • SCM sp. z o.o. (LLC)
  • Poznan, Poland, 61-737
    • Clinical Research Center Limited liability company Medic-R Limited partnership
  • Wieliszew, Poland, 05-135
    • Mazovian Oncology Hospital, Subdepartment of Urology
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia, Clinic of Urology
  • Belgrade, Serbia, 11080
    • Clinical Hospital Center Bezanijska Kosa, Clinic of Surgery, Department of Urology
  • Belgrade, Serbia, 11080
    • Clinical Hospital Center Zemun, Urology unit
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac, Clinic of Urology, Nephrology and Dialysis
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Bilbao, Spain, 48013
    • Hospital de Basurto
  • Madrid, Spain, 28046
    • La Paz University Hospital
  • Madrid, Spain, 28040
    • University Hospital Foundation Jimenez Diaz
  • Madrid, Spain, 28041
    • University Hospital 12 de Octubre
• United States
  • Arizona
    • Tucson, Arizona, United States, 85704
      • Arizona Urology Specialists
  • California
    • Loma Linda, California, United States, 92350
      • Loma Linda University Medical Center
    • San Diego, California, United States, 92123
      • Genesis Research
  • Kansas
    • Wichita, Kansas, United States, 67226
      • Wichita Urology Group
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • John Hopkins University
    • Hanover, Maryland, United States, 21076
      • Chesapeake Urology Research Associates
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health System
  • New York
    • Cheektowaga, New York, United States, 14225
      • Great Lakes Physician dba WNY Urology Associates
    • Garden City, New York, United States, 11530
      • AccuMed Research Associates
    • New York, New York, United States, 10016
      • NYU Langone Health
    • New York, New York, United States, 10029
      • Mount Sinai
    • New York, New York, United States, 10016
      • Manhattan Medical Research
  • Tennessee
    • Nashville, Tennessee, United States, 37209
      • Urology Associates, P.C.
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Research Institute
  • Washington
    • Spokane, Washington, United States, 99202
      • Spokane Urology, P.S.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Drug: UGN-102; 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 under chilled conditions, with subsequent conversion to a semi-solid gel depot following instillation into the bladder.; Other Names: UGN-102 (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 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.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) in Patients Who Achieved CR at the 3-month Visit	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.	Up to 60 months
Durable Complete Response (DCR) Rate in Patients Who Achieved CR at the 3-month Visit	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.	Up to 60 months
Disease-free Survival (DFS) in Patients Who Achieved CR at the 3-month Visit	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.	Up to 63 months
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest	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.	Up to 21 months
Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values	The number of patients with each type of event is summarized.	6 months
Number of Participants With Post-baseline PCS Chemistry Values	The number of patients with each type of event is summarized.	6 months

Collaborators and Investigators

• Sponsor: UroGen Pharma Ltd.
• Investigators: Principal Investigator: Sandip Prasad, MD, Atlantic Health System

Publications and helpful links

General Publications

• Prasad SM, Shishkov D, Mihaylov NV, Khuskivadze A, Genov P, Terzi V, Kates M, Huang WC, Louie MJ, Raju S, Burger B, Meads A, Schoenberg M. Primary Chemoablation of Recurrent Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer With UGN-102: A Single-Arm, Open-Label, Phase 3 Trial (ENVISION). J Urol. 2025 Feb;213(2):205-216. doi: 10.1097/JU.0000000000004296. Epub 2024 Oct 24.
• Prasad SM, Shishkov D, Mihaylov NV, Genov P, Terzi V, Kates M, Huang WC, Louie MJ, Burger B, Meads A, Schoenberg M. UGN-102 for Recurrent Low-Grade Intermediate-Risk Non-Muscle-Invasive Bladder Cancer: A 24-Month Duration of Response Results From the Phase 3 ENVISION Trial. J Urol. 2026 Mar 25:101097JU0000000000005041. doi: 10.1097/JU.0000000000005041. Online ahead of print.
• Stover AM, Mueller D, Carda-Auten J, Hilton A, Tsurutis V, Smith AB. Perceived Impact on Patient Routines/Responsibilities for Surgery and a Nonsurgical Primary Treatment Option in Recurrent Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer: Findings From the ENVISION Phase 3 Trial. J Urol. 2025 Jul;214(1):18-31. doi: 10.1097/JU.0000000000004511. Epub 2025 Mar 6.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Actual): April 26, 2023
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: February 7, 2022
• First Submitted That Met QC Criteria: February 7, 2022
• First Posted (Actual): February 17, 2022

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: NMIBC; Non-muscle invasive bladder cancer; Mitomycin; Low grade non-muscle invasive bladder cancer; Intermediate risk non-muscle invasive bladder cancer; UGN-102
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indoles; Quinones; Azirines; Mitomycins; Indolequinones; Mitomycin
• Other Study ID Numbers: BL011

Drug and device information, study documents

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