A Phase 3 Single-arm Study of UGN-104 for the Treatment of LG-UTUC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Urogen Pharma Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Oct 2025 → ongoing

Decision date (initial)

2025-10-10

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

UroGen Pharma Ltd.

External identifiers

EU CT number

2024-519343-15-00

WHO UTN

U1111-1315-1121

ClinicalTrials.gov

NCT06774131

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Therapy

Primary objective: To evaluate the tumor ablative effect of UGN-104, a novel formulation of UGN-101, in patients with LG-UTUC.

Secondary objectives 4

1. To evaluate the durability of response with respect to DOR and DCR rate at scheduled disease assessment time points.
2. To evaluate the safety and tolerability of UGN-104 in patients with LG-UTUC.
3. To assess the PK profile of mitomycin in plasma in a subgroup of patients treated with UGN-104.
4. Exploratory: To assess the effect of UGN-104 on PRO measures including quality of life, treatment satisfaction, and PGI-C.

Conditions and MedDRA coding

Low-grade Upper Tract Urothelial Cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

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. Naive or recurrent patients with LG, non-invasive UTUC in the pyelocalyceal system, with the following disease characteristics: a. 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. b. 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. c. Patient should have at least 1 remaining papillary LG tumor evaluated visually with a diameter of at least 5 mm post-biopsy. d. Wash urine cytology sampled from the pyelocalyceal system documenting the absence of high-grade (HG) UC, diagnosed not more than 8 weeks before Screening. e. 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 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.
4. Patients with Eastern Cooperative Oncology Group (ECOG) performance status < 3 (with Karnofsky > 40) (see Appendix 1).
5. Patients with life expectancy > 24 months at time of Screening.
6. Patients must have adequate organ and bone marrow function as determined by the following routine laboratory tests: a. Leukocytes ≥ 3,000/μL (≥ 3 × 109/L). b. Absolute neutrophil count ≥ 1,500/μL (≥ 1.5 × 109/L). c. Platelets ≥ 100,000/μL (≥ 100 × 109/L). d. Hemoglobin ≥ 9.0 g/dL. e. Total bilirubin ≤ 1.5 × upper limit of normal (ULN). f. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN. g. Alkaline phosphatase ≤ 2.5 × ULN. h. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min.
7. 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 PI.
8. 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 11

1. UC specific exclusions: a. Patient received Bacillus Calmette-Guérin (BCG) treatment for UC during the 6 months before enrollment. b. 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. c. Patient has a history of carcinoma in situ (CIS) in the urinary tract. d. Patient has a history of invasive UC in the past 5 years. e. 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: a. Basal or squamous cell skin cancers. b. Noninvasive cancer of the cervix. c. Any other cancer deemed to be of low risk for progression or patient morbidity during the study period.
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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary Endpoint: CRR, defined as the proportion of patients who achieve CR at the PDE Visit (5 ± 1 weeks after the sixth instillation of UGN-104) as determined by wash urine cytology, ureteroscopy, and for cause biopsy.

Secondary endpoints 6

1. DOR in patients who achieved CR at the PDE Visit, defined as the time from the date of evidence of CR at the PDE Visit to the earliest date of recurrence, progression or death as determined using the date of cytology, ureteroscopy, or for cause biopsy, or death due to any cause, whichever occurs first.
2. DCR rate at scheduled disease assessment time points, defined as the proportion of patients who achieve CR at the PDE Visit and maintain CR (ie, no detectable disease) up to that particular follow-up disease assessment.
3. Safety and tolerability will be evaluated through the reporting of AEs, including SAEs and AESIs, and through standard clinical and laboratory tests (eg, hematology and chemistry, urinalysis, physical examination, and vital signs).
4. Concentration data and PK parameters (Cmax, tmax, AUC, t1/2, and λZ).
5. Exploratory: Changes from baseline in patient scores on the QLQ-C30 and TSQM questionnaires.
6. Exploratory: Proportion of study participants reporting improvement at end of study on the PGI-C. The proportion reporting improvement over time will also be assessed to understand when change occurred.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Urogen Pharma Ltd.

Sponsor organisation

Urogen Pharma Ltd.

Address

9 Ha-Ta'Asiya

City

Ra'Anana

Postcode

4365405

Country

Israel

Scientific contact point

Organisation

Urogen Pharma Ltd.

Contact name

Sebastian Mirkin

Public contact point

Organisation

Urogen Pharma Ltd.

Contact name

Sebastian Mirkin

Third parties 1

Locations

6 EU/EEA countries · 41 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 90 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications