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

NCT06774131 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: UT0022024-519343-15-00
• Study Type: interventional
• Target: 70
• Locations: 8 countries
• Sites: 52

Brief Summary

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).

Conditions

Upper Urinary Tract Urothelial Carcinoma; Urothelial Carcinoma

Keywords

UTUC; Low Grade UTUC; Low-grade Upper Tract Urothelial Cancer; UGN-104; Mitomycin; Nephrostomy Tube; LG-UTUC; UGN-101

Outcome Measures

Primary Outcomes (1)

• Complete response rate (CRR)

  CRR is defined as the proportion of patients who achieved CR at the PDE Visit.

  3 months

Secondary Outcomes (8)

• Duration of response (DOR)

  12 months

• Durable complete response (DCR) rate

  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)

  15 months

• Mitomycin plasma concentrations

  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)

  0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-104

Study Arms (1)

UGN-104

EXPERIMENTAL

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

Interventions

UGN-104 DRUG

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.

Also known as: UGN-104 (mitomycin) for pyelocalyceal solution

UGN-104

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and protocol.
• Naive or recurrent patients with LG, non-invasive UTUC in the pyelocalyceal system, with the following disease characteristics:
• 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.
• 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.
• Patient should have at least 1 remaining papillary LG tumor evaluated visually with a diameter of at least 5 mm post-biopsy.
• Wash urine cytology sampled from the pyelocalyceal system documenting the absence of high-grade (HG) UC, diagnosed not more than 8 weeks before Screening.
• Patients with Eastern Cooperative Oncology Group (ECOG) performance status \< 3 (with Karnofsky \> 40).
• Patients with life expectancy \> 24 months at time of Screening.
• Patients must have adequate organ and bone marrow function as determined by the following routine laboratory tests:
• Leukocytes ≥ 3,000/μL (≥ 3 × 10\^9/L).
• Absolute neutrophil count ≥ 1,500/μL (≥ 1.5 × 10\^9/L).
• Platelets ≥ 100,000/μL (≥ 100 × 10\^9/L).
• Hemoglobin ≥ 9.0 g/dL.
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN.

You may not qualify if:

• Patient received Bacillus Calmette-Guérin (BCG) treatment for UC during the 6 months before enrollment.
• 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.
• Patient has a history of carcinoma in situ (CIS) in the urinary tract.
• Patient has a history of invasive UC in the past 5 years.
• Patient has a history of HG papillary UC in the urinary tract in the past 2 years.
• Patient is actively being treated or intends to be treated with systemic chemotherapy during the duration of the study.
• Any other malignancy diagnosed within 2 years before enrollment with the exception of:
• Basal or squamous cell skin cancers.
• Noninvasive cancer of the cervix.
• Any other cancer deemed to be of low risk for progression or patient morbidity during the study period in the opinion of the investigator.
• 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).
• Known allergy or sensitivity to any component of the study treatment (including excipients) that in the investigator's opinion cannot be readily managed.
• Patient has an intractable bleeding disorder (eg, coagulation factors deficiencies, Von Willebrand disease).
• 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.
• Patient was previously treated with JELMYTO (product code UGN-101) for UTUC.

Sponsors & Collaborators

• UroGen Pharma Ltd.: lead

Study Sites (52)

Urology Centers of Alabama

Homewood, Alabama, 35209, United States

RECRUITING

Arizona State Urological Research Institute, LLC ("ASURI")

Chandler, Arizona, 85225, United States

RECRUITING

1155 E. Combs Rd, Suite 105, Queen Creek, AZ, 85140, USA

Queen Creek, Arizona, 85140, United States

RECRUITING

Michael G Oefelein Clinical Trials

Bakersfield, California, 93301, United States

RECRUITING

University of California, Irvine

Orange, California, 92868, United States

RECRUITING

BioResearch Partners Aventura

Aventura, Florida, 33180, United States

RECRUITING

UF Health Cancer Center University of Florida

Gainesville, Florida, 32610, United States

RECRUITING

BioResearch Partners Hialeah

Hialeah, Florida, 33013, United States

RECRUITING

D&H National Research Centers - Cancer Research Center, LLC

Margate, Florida, 33063, United States

RECRUITING

Urology Center of Iowa Research

Clive, Iowa, 50325, United States

RECRUITING

The Urology Center, P.C.

Omaha, Nebraska, 68114, United States

RECRUITING

Montefiore Medical Center - Bronx

The Bronx, New York, 10461, United States

RECRUITING

University of Cincinnati Medical Center (UCMC)

Cincinnati, Ohio, 45219, United States

RECRUITING

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210, United States

RECRUITING

Urologic Specialists of Oklahoma

Tulsa, Oklahoma, 74146-5830, United States

RECRUITING

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Carolina Urologic Research Center, LLC

Myrtle Beach, South Carolina, 29572, United States

RECRUITING

Low county Urology Clinics

North Charleston, South Carolina, 29406, United States

RECRUITING

Amarillo Urology Research

Amarillo, Texas, 79106, United States

RECRUITING

UPNT Research Institute, LLC

Arlington, Texas, 76017, United States

RECRUITING

Texas Urology Specialists-Austin

Austin, Texas, 78705, United States

RECRUITING

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, 22908, United States

RECRUITING

MHAT Haskovo AD

Haskovo, 6300, Bulgaria

RECRUITING

University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov," Sofia, Clinic of Urology

Sofia, 1000, Bulgaria

RECRUITING

LTD "Israel-Georgian Medical Research Clinic "Healthycore"

Tbilisi, 0112, Georgia

RECRUITING

JSC "Vian"-I.Bokeria University Hospital

Tbilisi, 0137, Georgia

RECRUITING

LTD "Geo Hospitals"

Tbilisi, 0144, Georgia

RECRUITING

LTD "Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic"

Tbilisi, 0144, Georgia

RECRUITING

University of Debrecen Clinical Center, Department of Urology

Debrecen, 4032, Hungary

RECRUITING

Carmel Medical Center

Haifa, 3436212, Israel

RECRUITING

Meir Medical Center, Department of Urology

Kefar Sava, 4428164, Israel

RECRUITING

Rabin Medical Center - Hasharon hospital

Petah Tikva, 4937211, Israel

RECRUITING

Sheba Medical Center

Ramat Gan, 5262000, Israel

RECRUITING

Sheba Medical Center

Ramat Gan, 5262000, Israel

RECRUITING

Assaf Harofeh hospital, Shamir Medical Center

Ẕerifin, 70500, Israel

RECRUITING

IN-VIVO Limited Liability Company

Bydgoszcz, 85-048, Poland

RECRUITING

NZOZ Silesian Urology Hospital

Katowice, 40-073, Poland

RECRUITING

St. John of Dukla Oncology Center of Lublin Land

Lublin, 20-090, Poland

RECRUITING

Clinical Hospital of the Ministry of Internal Affairs and Administration with Warmia and Mazury Oncology Centre in Olsztyn

Olsztyn, 10-228, Poland

RECRUITING

Independent Public Teaching Hospital #2

Szczecin, 70-111, Poland

RECRUITING

Jan Mikulicz-Radecki University Clinical Hospital in Wroclaw

Wroclaw, 50-556, Poland

RECRUITING

Municipal Clinical Hospital Cluj-Napoca

Cluj-Napoca, 400139, Romania

RECRUITING

Regional Institute of Oncology Iasi

Iași, 700483, Romania

RECRUITING

Bihor County Emergency Clinical Hospital

Oradea, 410169, Romania

RECRUITING

Timisoara County Clinical Emergency Hospital Pius Brinzeu

Timișoara, 300723, Romania

RECRUITING

15006

A Coruña, Galicia, Spain

RECRUITING

Hospital Universitario Puerta del Mar

Cadiz, 11009, Spain

RECRUITING

Hospital Universitario Reina Sofía

Córdoba, 14004, Spain

RECRUITING

Hospital General Universitario Morales Meseguer

Murcia, 30008, Spain

RECRUITING

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

RECRUITING

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

Mitomycin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Derrick McKinley, MD

  UroGen Pharma

  STUDY DIRECTOR

Central Study Contacts

Renee Sumlin

CONTACT

346-573-2671; renee.sumlin@urogen.com

Yafit Makmal

CONTACT

yafit.makmal@urogen.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2025
• First Posted: January 14, 2025
• Study Start: August 6, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: April 29, 2026

Record last verified: 2026-04

Locations

BU (2); HU (1); IL (6); GE (4); PL (6); US (23); ES (6); RO (4)