A Phase 3 Single-arm Study of UGN-104 for the Treatment of Low-grade Upper Tract Urothelial Cancer

April 28, 2026 updated by: UroGen Pharma Ltd.

A Phase 3, Single-arm, Multicenter Study to Evaluate the Efficacy and Safety of UGN-104, a Novel Formulation of UGN-101, for the Treatment of Patients With Low-grade Upper Tract Urothelial Cancer (LG-UTUC)

This study will evaluate the efficacy and safety of UGN-104, a new formulation of UGN-101 (approved in the United States and Israel as JELMYTO [mitomycin] for pyelocalyceal solution), instilled in the upper urinary tract (UUT) of patients with low-grade upper tract urothelial cancer (LG-UTUC).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Eligible patients will be treated with UGN-104 once weekly for 6 weeks (a total of 6 doses).

Efficacy will be assessed by the complete response rate (CRR) at the Primary Disease Evaluation (PDE) Visit (approximately 3 months after the first instillation). Response will be determined based on central laboratory interpretation of UUT wash urine cytology and visual evaluation (ureteroscopy). Biopsy of any remaining or new lesions will be performed where technically feasible and the central laboratory histopathology assessment will also be used in the response determination, if applicable.

Patients who have a complete response (CR) at the PDE Visit, defined as having no detectable disease (NDD), will enter the Follow-up Period of the study. During the Follow-up Period, patients may receive UGN-104 as maintenance treatment at the discretion of the investigator. The maintenance regimen is once monthly for 11 months (a total of 11 doses) and should start as soon as possible (no longer than 3 weeks) after CR is determined at the PDE Visit.

All patients in the Follow-up Period, regardless of whether they receive maintenance treatment, will return to the clinic every 3 months for evaluation of response and will remain on study for 12 months after the PDE Visit or until disease recurrence, disease progression, or death, whichever occurs first.

Patients who have a non-complete response (NCR) at the PDE Visit will be considered to have completed the study.

Study Type

Interventional

Enrollment (Estimated)

70

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Bulgaria
      • Haskovo, Bulgaria, 6300
        • Recruiting
        • MHAT Haskovo AD
        • Contact:
        • Principal Investigator:
          • Ivan Nikolov
      • Sofia, Bulgaria, 1000
        • Recruiting
        • University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov," Sofia, Clinic of Urology
        • Contact:
        • Principal Investigator:
          • Boris Mladenov
  • Georgia
      • Tbilisi, Georgia, 0144
        • Recruiting
        • LTD "Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic"
        • Contact:
        • Principal Investigator:
          • Shalva Chovelidze
      • Tbilisi, Georgia, 0112
        • Recruiting
        • LTD "Israel-Georgian Medical Research Clinic "Healthycore"
        • Principal Investigator:
          • Ekaterine Arkania
        • Contact:
      • Tbilisi, Georgia, 0137
        • Recruiting
        • JSC "Vian"-I.Bokeria University Hospital
        • Contact:
        • Principal Investigator:
          • Koba Kiknavelidze
      • Tbilisi, Georgia, 0144
        • Recruiting
        • LTD "Geo Hospitals"
        • Contact:
        • Principal Investigator:
          • Giorgia Adeishvili
  • Hungary
      • Debrecen, Hungary, 4032
        • Recruiting
        • University of Debrecen Clinical Center, Department of Urology
        • Contact:
        • Principal Investigator:
          • Tibor Flasko, MD
  • Israel
      • Haifa, Israel, 3436212
        • Recruiting
        • Carmel Medical Center
        • Contact:
        • Principal Investigator:
          • Yuval Freifeld
      • Kefar Sava, Israel, 4428164
        • Recruiting
        • Meir Medical Center, Department of Urology
        • Contact:
        • Principal Investigator:
          • Omri Schwarztuch Gildor
      • Petah Tikva, Israel, 4937211
        • Recruiting
        • Rabin Medical Center - Hasharon Hospital
        • Contact:
        • Principal Investigator:
          • David Lifshitz
      • Ramat Gan, Israel, 5262000
        • Recruiting
        • Sheba Medical Center
        • Principal Investigator:
          • Nir Kleinmann
        • Contact:
      • Ẕerifin, Israel, 70500
        • Recruiting
        • Assaf Harofeh hospital, Shamir Medical Center
        • Contact:
        • Principal Investigator:
          • Amnon Zisman
  • Poland
      • Bydgoszcz, Poland, 85-048
        • Recruiting
        • IN-VIVO Limited Liability Company
        • Principal Investigator:
          • Piotr Piasecki
        • Contact:
      • Katowice, Poland, 40-073
        • Recruiting
        • NZOZ Silesian Urology Hospital
        • Contact:
        • Principal Investigator:
          • Igal Mor
      • Lublin, Poland, 20-090
        • Recruiting
        • St. John of Dukla Oncology Center of Lublin Land
        • Principal Investigator:
          • Robert Klijer, MD
        • Contact:
      • Olsztyn, Poland, 10-228
        • Recruiting
        • Clinical Hospital of the Ministry of Internal Affairs and Administration with Warmia and Mazury Oncology Centre in Olsztyn
        • Contact:
        • Principal Investigator:
          • Roman Sosnowski, MD
      • Szczecin, Poland, 70-111
        • Recruiting
        • Independent Public Teaching Hospital #2
        • Contact:
        • Principal Investigator:
          • Marcin Slojewski, MD
      • Wroclaw, Poland, 50-556
        • Recruiting
        • Jan Mikulicz-Radecki University Clinical Hospital in Wroclaw
        • Contact:
        • Principal Investigator:
          • Anna Kołodziej
  • Romania
      • Cluj-Napoca, Romania, 400139
        • Recruiting
        • Municipal Clinical Hospital Cluj-Napoca
        • Contact:
        • Principal Investigator:
          • Ramona Doina Matei
      • Iași, Romania, 700483
        • Recruiting
        • Regional Institute of Oncology Iasi
        • Contact:
        • Principal Investigator:
          • Teodora Alexa Stratulat
      • Oradea, Romania, 410169
        • Recruiting
        • Bihor County Emergency Clinical Hospital
        • Contact:
        • Principal Investigator:
          • Mihail Claudius Berechet
      • Timișoara, Romania, 300723
        • Recruiting
        • Timisoara County Clinical Emergency Hospital Pius Brinzeu
        • Contact:
        • Principal Investigator:
          • Razvan Tiberiu Bardan
  • Spain
      • Cadiz, Spain, 11009
        • Recruiting
        • Hospital Universitario Puerta del Mar
        • Contact:
        • Principal Investigator:
          • Jesús Rosety Rodriguez
      • Córdoba, Spain, 14004
        • Recruiting
        • Hospital Universitario Reina Sofia
        • Contact:
        • Principal Investigator:
          • Juan Manuel Rubio Galisteo
      • Murcia, Spain, 30008
        • Recruiting
        • Hospital General Universitario Morales Meseguer
        • Contact:
        • Principal Investigator:
          • Tomás Fernández Aparicio
      • Seville, Spain, 41009
        • Recruiting
        • Hospital Universitario Virgen Macarena
        • Contact:
        • Principal Investigator:
          • Carlos González Cáliz
      • Valencia, Spain, 46010
        • Recruiting
        • Hospital Clínico Universitario de Valencia
        • Contact:
        • Principal Investigator:
          • Jose María Martinez Jabaloyas
    • Galicia
      • A Coruña, Galicia, Spain
        • Recruiting
        • 15006
        • Contact:
        • Principal Investigator:
          • Dario Vazquez-Martul
  • United States
    • Alabama
      • Homewood, Alabama, United States, 35209
        • Recruiting
        • Urology Centers of Alabama
        • Contact:
        • Principal Investigator:
          • Michael Eric Brewer
    • Arizona
      • Chandler, Arizona, United States, 85225
        • Recruiting
        • Arizona State Urological Research Institute, LLC ("ASURI")
        • Contact:
        • Principal Investigator:
          • Pratik Patel
      • Queen Creek, Arizona, United States, 85140
        • Recruiting
        • 1155 E. Combs Rd, Suite 105, Queen Creek, AZ, 85140, USA
        • Principal Investigator:
          • Harpreet Wadhwa, MD
        • Contact:
    • California
      • Bakersfield, California, United States, 93301
        • Recruiting
        • Michael G Oefelein Clinical Trials
        • Contact:
        • Principal Investigator:
          • Michael Oefelein
      • Orange, California, United States, 92868
        • Recruiting
        • University of California, Irvine
        • Contact:
        • Principal Investigator:
          • Edward Uchio
    • Florida
      • Aventura, Florida, United States, 33180
        • Recruiting
        • BioResearch Partners Aventura
        • Contact:
        • Principal Investigator:
          • Angelo Gousse
      • Gainesville, Florida, United States, 32610
        • Recruiting
        • UF Health Cancer Center University of Florida
        • Contact:
        • Principal Investigator:
          • Padraic O Malley
      • Hialeah, Florida, United States, 33013
        • Recruiting
        • BioResearch Partners Hialeah
        • Principal Investigator:
          • Luis Rangel
        • Contact:
      • Margate, Florida, United States, 33063
        • Recruiting
        • D&H National Research Centers - Cancer Research Center, LLC
        • Contact:
        • Principal Investigator:
          • Emilio Araujo-Mino, MD
    • Iowa
      • Clive, Iowa, United States, 50325
        • Recruiting
        • Urology Center of Iowa Research
        • Contact:
        • Principal Investigator:
          • Brian Gallagher
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Recruiting
        • The Urology Center, P.C.
        • Contact:
        • Principal Investigator:
          • Jennifer Dwyer
    • New York
      • The Bronx, New York, United States, 10461
        • Recruiting
        • Montefiore Medical Center - Bronx
        • Contact:
        • Principal Investigator:
          • Alexander Small, MD
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Recruiting
        • University of Cincinnati Medical Center (UCMC)
        • Contact:
        • Principal Investigator:
          • Alberto Maritini
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The James Cancer Hospital and Solove Research Institute
        • Contact:
        • Principal Investigator:
          • Ahmad Shabsigh, MD
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74146-5830
        • Recruiting
        • Urologic Specialists of Oklahoma
        • Principal Investigator:
          • John Forrest, MD
        • Contact:
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Recruiting
        • Penn State Milton S Hershey Medical Center
        • Principal Investigator:
          • Jay Raman
        • Contact:
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina
        • Contact:
        • Principal Investigator:
          • Matvey Tsivian
      • Myrtle Beach, South Carolina, United States, 29572
        • Recruiting
        • Carolina Urologic Research Center, LLC
        • Contact:
        • Principal Investigator:
          • Abhishek Srivastava
      • North Charleston, South Carolina, United States, 29406
        • Recruiting
        • Low county Urology Clinics
        • Contact:
        • Principal Investigator:
          • Justin Ellett
    • Texas
      • Amarillo, Texas, United States, 79106
        • Recruiting
        • Amarillo Urology Research
        • Contact:
        • Principal Investigator:
          • David Wilhelm
      • Arlington, Texas, United States, 76017
        • Recruiting
        • UPNT Research Institute, LLC
        • Contact:
        • Principal Investigator:
          • Harrison Abrahams
      • Austin, Texas, United States, 78705
        • Recruiting
        • Texas Urology Specialists-Austin
        • Contact:
        • Principal Investigator:
          • Kyle Keyes
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Recruiting
        • University of Virginia Comprehensive Cancer Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Tracy Krupski

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 and protocol.

  2. Naive or recurrent patients with LG, non-invasive UTUC in the pyelocalyceal system, with the following disease characteristics:

    1. At least 1 measurable papillary LG tumor, evaluated visually, ≤ 15 mm. The largest lesion should not exceed 15 mm. Debulking to ≤ 15 mm is permitted.
    2. Biopsy taken from at least 1 tumor located above the ureteropelvic junction revealing LG urothelial carcinoma (UC). Patients who have been biopsied within 8 weeks before Screening for this study and shown to have LG UC may have these historical biopsies used for enrollment into the study and do not require repeat biopsy during Screening.
    3. Patient should have at least 1 remaining papillary LG tumor evaluated visually with a diameter of at least 5 mm post-biopsy.
    4. Wash urine cytology sampled from the pyelocalyceal system documenting the absence of high-grade (HG) UC, diagnosed not more than 8 weeks before Screening.
    5. Patients with bilateral LG-UTUC may be enrolled if at least 1 side meets the inclusion criteria for the study and if the other kidney does not require further treatments. (The disease in the other kidney must be completely ablated before receiving treatment in the study.) Note: If both upper tracts meet inclusion criteria, the treating urologist in consultation with the sponsor's medical monitor can decide which side to treat in the study. The pyelocalyceal system not under study must be free of cancer before the first instillation on the side to be treated in the study.
  3. Patients with Eastern Cooperative Oncology Group (ECOG) performance status < 3 (with Karnofsky > 40).
  4. Patients with life expectancy > 24 months at time of Screening.

  5. Patients must have adequate organ and bone marrow function as determined by the following routine laboratory tests:

    1. Leukocytes ≥ 3,000/μL (≥ 3 × 10^9/L).
    2. Absolute neutrophil count ≥ 1,500/μL (≥ 1.5 × 10^9/L).
    3. Platelets ≥ 100,000/μL (≥ 100 × 10^9/L).
    4. Hemoglobin ≥ 9.0 g/dL.
    5. Total bilirubin ≤ 1.5 × upper limit of normal (ULN).
    6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN.
    7. Alkaline phosphatase ≤ 2.5 × ULN.
    8. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min.
  6. Patient has no active urinary tract infection (UTI) as confirmed by urine culture or urinalysis. Note: In case of a symptomatic UTI the patient will be treated with antibiotics and the instillation will be postponed until resolution. In the case of asymptomatic bacteriuria, the use of prophylactic antibiotics and postponement of treatment is at the discretion of the investigator.
  7. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for clinical study participants.

Female patients of childbearing potential (defined as premenopausal women who have not been sterilized) and male patients with female partners of childbearing potential must agree to use 2 acceptable forms of effective contraception from enrollment through 6 months post treatment. Sexually active male patients must agree to use a condom during intercourse for at least 48 hours after each instillation.

Acceptable methods of birth control considered to have a low failure rate (ie, less than 1% per year) when used consistently and correctly include 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, post-ovulation methods) is NOT an acceptable method of contraception.

Exclusion Criteria:

  1. UC specific exclusions:

    1. Patient received Bacillus Calmette-Guérin (BCG) treatment for UC during the 6 months before enrollment.
    2. The patient has untreated concurrent UC in locations other than the target area (unless treated and resolved during Screening); ie, ureteral and lower urinary tract tumors must be completely ablated before entry.
    3. Patient has a history of carcinoma in situ (CIS) in the urinary tract.
    4. Patient has a history of invasive UC in the past 5 years.
    5. Patient has a history of HG papillary UC in the urinary tract in the past 2 years.
  2. Patient is actively being treated or intends to be treated with systemic chemotherapy during the duration of the study.

  3. Any other malignancy diagnosed within 2 years before enrollment with the exception of:

    1. Basal or squamous cell skin cancers.
    2. Noninvasive cancer of the cervix.
    3. Any other cancer deemed to be of low risk for progression or patient morbidity during the study period in the opinion of the investigator.
  4. Patient with urinary obstruction such that there is an inability to deliver the study treatment to the pyelocalyceal system either via ureteral catheter (retrograde administration) or nephrostomy tube (antegrade administration).
  5. Known allergy or sensitivity to any component of the study treatment (including excipients) that in the investigator's opinion cannot be readily managed.
  6. Patient has an intractable bleeding disorder (eg, coagulation factors deficiencies, Von Willebrand disease).
  7. Patient is currently receiving any other investigational product, has participated in a research protocol involving administration of an investigational product in the past 30 days, or plans to participate in a research protocol involving administration of an investigational product during study conduct.
  8. Patient was previously treated with JELMYTO (product code UGN-101) for UTUC.
  9. Women who are pregnant (positive urine or serum pregnancy test), planning to become pregnant during the study period, or who are breastfeeding are not eligible to enroll.
  10. Patient has any other medical or mental condition(s) that make(s) his/her participation in the study unadvisable in the opinion of the investigator.
  11. 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: UGN-104

Patients will receive UGN-104 once weekly for 6 weeks (a total of 6 doses). The dose of UGN-104 to be instilled is 4 mg mitomycin per 1 mL sterile hydrogel via ureteral catheter (retrograde administration) or nephrostomy tube (antegrade administration).

Patients who have a CR at the PDE Visit will enter the Follow-up Period and may receive UGN-104 as maintenance treatment once monthly for 11 months (a total of 11 doses) at the discretion of the investigator.
Drug: UGN-104
UGN-104 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-104 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 UUT.
Other Names:
  • UGN-104 (mitomycin) for pyelocalyceal solution

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of response (DOR)
Time Frame: 12 months
DOR is defined as the time from the date of evidence of CR at the PDE Visit to the earliest date of recurrence, progression, or death due to any cause, whichever occurred first.
12 months
Durable complete response (DCR) rate
Time Frame: 12 months
DCR rate at scheduled disease assessment time points, defined as the proportion of patients who achieved CR at the PDE Visit and maintained CR (ie, no detectable disease) up to that particular follow-up disease assessment.
12 months
Incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of special interest, and abnormal clinical laboratory test results (hematology and serum chemistry)
Time Frame: 15 months
The number of patients with each type of event will be summarized.
15 months
Mitomycin plasma concentrations
Time Frame: 0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-104
Mitomycin plasma concentrations will be assessed in a subset of patients treated with UGN-104.
0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-104
Mitomycin maximum plasma concentration (Cmax)
Time Frame: 0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-104
Mitomycin Cmax will be assessed in a subset of patients treated with UGN-104.
0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-104
Mitomycin time to maximum plasma concentration (tmax)
Time Frame: 0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-104
Mitomycin tmax will be assessed in a subset of patients treated with UGN-104.
0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-104
Mitomycin area under the concentration-time curve (AUC)
Time Frame: 0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-104
Mitomycin AUC will be assessed in a subset of patients treated with UGN-104.
0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-104
Mitomycin terminal half-life (t1/2)
Time Frame: 0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-104
Mitomycin t1/2 will be assessed in a subset of patients treated with UGN-104.
0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-104

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UroGen Pharma Ltd.

Investigators

  • Study Director: Derrick McKinley, MD, UroGen Pharma

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 6, 2025

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

March 1, 2028

Study Registration Dates

First Submitted

January 8, 2025

First Submitted That Met QC Criteria

January 8, 2025

First Posted (Actual)

January 14, 2025

Study Record Updates

Last Update Posted (Actual)

April 29, 2026

Last Update Submitted That Met QC Criteria

April 28, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UT002
  • 2024-519343-15-00 (Ctis)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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