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Non-muscle Invasive Bladder CancerPhase 1NCT05375903

A Phase 1 Dose-escalation Study of UGN-301 in Patients With Recurrent Non-muscle Invasive Bladder Cancer (NMIBC)

A Phase 1 study testing UGN-301, UGN-201 and Gemcitabine in people with Non-muscle Invasive Bladder Cancer and NMIBC, run by UroGen Pharma Ltd. at 13 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is being conducted to evaluate the safety and determine the recommended Phase 2 dose (RP2D) of UGN-301 (zalifrelimab) administered intravesically as monotherapy and in combination with other agents in patients with recurrent NMIBC. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
UGN-301, UGN-201 and Gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
13 sitesin 3 countries
Study dates
1 Jun 2022to 9 Jan 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Able to give informed consent.
  • Arm A: Have confirmed recurrent NMIBC with HG Ta and/or T1 disease and/or CIS or recurrent IR LG Ta and/or T1 disease.
  • Arm B: Have confirmed recurrent NMIBC with HG Ta and/or T1 disease and/or CIS. Arm C: Have confirmed recurrent NMIBC with HG Ta and/or T1 disease and/or CIS.
  • Patients with HG Ta and/or T1 disease and/or CIS must meet one of the following criteria:
  • Have Bacillus Calmette-Guérin (BCG)-unresponsive disease, defined as 1) persistent or recurrent CIS alone or with recurrent Ta/T1 disease within 12 months of completion of adequate BCG therapy, or 2) recurrent HG Ta/T1 disease within 6 months of completion of adequate BCG therapy, or 3) HG T1 disease at the first evaluation following a BCG induction course.
  • Notes: Adequate BCG therapy is defined as at least 5 of 6 doses of an initial induction course plus 1) at least 2 of 3 doses of maintenance therapy or 2) at least 2 of 6 doses of a second induction course. Patients with BCG-unresponsive disease also must be unwilling or unfit to undergo radical cystectomy.
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  • Have otherwise failed adequate BCG therapy (eg, recurrence > 6 months [papillary] or > 12 months [CIS] after last BCG exposure).
  • Are BCG intolerant, defined as the inability to tolerate at least one full induction course of BCG.
  • Have HG Ta disease with tumors ≤ 3 cm and failed at least one previous course of therapy (eg, adjuvant intravesical chemotherapy).
  • Have all papillary tumors visible by white light resected, and obvious areas of CIS fulgurated during Screening or within 6 weeks before Screening. Note: Blue light cystoscopy is not permitted.
  • Eastern Cooperative Oncology Group (ECOG) status ≤ 2.
  • Absence of concomitant upper tract urothelial carcinoma (UTUC) or urothelial carcinoma (UC) within the prostatic urethra. Freedom from upper tract disease (if clinically indicated) as indicated by no evidence of upper tract tumor by either intravenous pyelogram, retrograde pyelogram, computerized tomography (CT) urogram with or without contrast, or magnetic resonance imaging (MRI) urogram with or without contrast performed within 6 months of enrollment.
  • Patients with prostate cancer on active surveillance at very low, low, or intermediate risk for progression, defined as Gleason Grade Group 1 or 2, Gleason score ≤ 7, with prostate-specific antigen < 20 ng/dL, and cT1-cT2b (NCCN, 2023) are permitted to be in the study at the discretion of the investigator (see exclusion criterion 8).
  • Female patients of childbearing potential must use maximally effective birth control during the period of therapy, must be willing to use contraception for 1 month following the last administration of study drug and must have a negative urine or serum pregnancy test upon entry into this study. Otherwise, female patients must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile. "Maximally effective birth control" means that the patient, if sexually active, should be using a combination of 2 methods of birth control that are approved and recognized to be effective by health authorities.
  • Male patients must be surgically sterile or willing to use 2 highly effective forms of birth control upon enrollment, during the course of the study, and for 1 month following the last study drug instillation.
  • Has adequate organ and bone marrow function within 14 days of treatment initiation as determined by routine laboratory tests outlined below:
  • Leukocytes ≥ 3,000/μL;
  • Absolute neutrophil count (ANC) ≥ 1,500/μL;
  • Platelets ≥ 100,000/μL;
  • Hemoglobin ≥ 9.0 g/dL;
  • Total bilirubin ≤ 1.5 × upper limit of normal (ULN);
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN;
  • Alkaline phosphatase (ALP) ≤ 2.5 × ULN;
  • Estimated creatinine clearance ≥ 30 mL/min calculated using the Cockcroft-Gault equation.
  • Has a life expectancy > 12 months.

Who cannot join

  • Current or previous evidence of muscle invasive, locally advanced nonresectable, or metastatic urothelial carcinoma (ie, T2, T3, T4 and/or stage IV).
  • Current systemic therapy for bladder cancer.
  • Prior therapy with an anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1), anti-PD-ligand 1 (L1) agent, or with an agent directed to another co-inhibitory T-cell receptor.
  • Active infection requiring systemic therapy including urinary tract infection (once satisfactorily treated, patients can enter the study).
  • Active systemic autoimmune disease that required systemic treatment in the past 2 years. Short courses of steroids (≤ 14 days) for medical reasons without anticancer intent (eg, atopic dermatitis, psoriasis, infection, allergic reaction) are permitted if the last dose was ≥ 4 weeks before the first dose of study treatment.
  • Women who are pregnant or nursing.
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  • Any medical psychological, familial, sociological, or geographical condition that, in the opinion of the Investigator, would preclude participation in the study.
  • History of malignancy of other organ system within the past 5 years, except previously treated UTUC, basal cell carcinoma or squamous cell carcinoma of the skin, and/or prostate cancer under active surveillance (see inclusion criterion 8).
  • Patients who cannot tolerate intravesical dosing or intravesical surgical manipulation.
  • Intravesical therapy within 4 weeks before starting study treatment.
  • Has participated in a study of an investigational agent and received study therapy or received investigational device within 4 weeks before the first dose of study treatment.
  • Has received an immune modulator therapy within 5 half-lives of starting study treatment.
  • Has received a vaccine within 2 weeks before starting study treatment.
  • Has a known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

Trial locations and contacts

13 sites in 3 countries.

13 sites in 3 countries

United States7 sites

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Arkansas Urology

    Little Rock, Arkansas, 72211

  • UCLA - University of California

    Los Angeles, California, 90095

  • Clinical Research Solutions

    Middleburg Heights, Ohio, 44130

  • Manhattan Medical Research

    New York, New York, 10016

  • Florida Urology Partners, LLC

    Tampa, Florida, 33615

Other trials in United States

Italy3 sites

  • I.R.C.C.S. Ospedale San Raffaele

    Milan

  • National Tumor Institute Fondazione G. Pascale

    Naples

  • Istituto Oncologico Veneto

    Padova

Other trials in Italy

Spain3 sites

  • NEXT Oncology IOB- Hospital Quironsalud Barcelona

    Barcelona, 08023

  • Hospital Clinic de Barcelona Instituto Clinic de Nefrologia y Urologia (ICNU)

    Barcelona, 08036

  • NEXT Oncology- Hospital Quironsalud Mardrid

    Madrid, 28223

Other trials in Spain

About this study

Official title: A Phase 1, Open-label, Dose-escalation Study to Investigate the Safety, Tolerability, and Pharmacokinetics of UGN-301 (Zalifrelimab) Administered Intravesically as Monotherapy and in Combination With Other Agents in Patients With Recurrent NMIBC

This study is being conducted to evaluate the safety and determine the recommended Phase 2 dose (RP2D) of UGN-301 (zalifrelimab) administered intravesically as monotherapy and in combination with other agents in patients with recurrent NMIBC.

Read the detailed description

This master protocol will comprise multiple treatment arms designed to independently investigate intravesical delivery of UGN-301 either as monotherapy or in combination with other agents. Initial study treatment arms will include:

  • UGN-301 monotherapy
  • UGN-301 + UGN-201 (imiquimod) in combination
  • UGN-301 + gemcitabine in combination

Additional study treatment arms investigating UGN-301 in combination with other agents may be added in the future.

The study will evaluate escalating doses of UGN-301 to determine the biologically effective dose (BED) and maximum tolerated dose (MTD) of UGN-301 either as monotherapy or in combination with other agents.

When evaluated in combination with other agents, the UGN-301 dose will begin at least 1 dose level lower than the highest dose level cleared in the monotherapy arm, or 1 dose level lower than the RP2D.

Eligible patients in each study treatment arm will enter a 12-week Induction Period.

Patients with noninvasive papillary carcinoma and/or tumor that invades the lamina propria (Ta and/or T1) who do not have disease recurrence and patients with carcinoma in situ (CIS) who have a complete response (CR) at 3 months after the start of treatment will return to the clinic for a Safety Follow-up Visit at 6 months after the start of treatment.

Ta/T1 patients without disease recurrence and CIS patients with CR at 6 months may enter an Optional Maintenance Period of up to 9 months.

Being tested
UGN-301, UGN-201, Gemcitabine
Medical subject headings
Non-Muscle Invasive Bladder Neoplasms, Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • UGN-301Drug

    Also called UGN-301 (zalifrelimab) intravesical solution

    Induction Period: Intravesical administration once weekly for 6 weeks.

    Optional Maintenance Period: Intravesical administration once every 3 months (at 6, 9, and 12 months after the start of treatment).

  • UGN-201Drug

    Also called UGN-201 (imiquimod) intravesical solution

    Induction Period: Intravesical administration once weekly for 6 weeks.

    Optional Maintenance Period: Intravesical administration once every 3 months (at 6, 9, and 12 months after the start of treatment).

  • GemcitabineDrug

    Induction Period: Intravesical administration once weekly for 6 weeks.

    Optional Maintenance Period: Intravesical administration once every 3 months (at 6, 9, and 12 months after the start of treatment).

Study groups in NCT05375903
Study groupRoleWhat they receive
UGN-301 monotherapy dose escalation (Arm A)ExperimentalDose escalation of UGN-301 monotherapy in patients with recurrent NMIBC with high grade (HG) Ta and/or T1 disease and/or CIS or recurrent intermediate risk (IR) low grade (LG) Ta and/or T1 disease.
Receives: Drug: UGN-301
UGN-301 dose escalation + UGN-201 combination (Arm B)ExperimentalDose escalation of UGN-301 in combination with a fixed dose of UGN-201 in patients with recurrent NMIBC with HG Ta and/or T1 disease and/or CIS.
Receives: Drug: UGN-301; Drug: UGN-201
UGN-301 dose escalation + gemcitabine combination (Arm C)ExperimentalDose escalation of UGN-301 in combination with a fixed dose of gemcitabine in patients with recurrent NMIBC with HG Ta and/or T1 disease and/or CIS.
Receives: Drug: UGN-301; Drug: Gemcitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs)

    The number of patients with each type of event will be summarized.

    Measured: Up to 15 months

  2. Concentration of UGN-301 in blood and urine

    Data will be summarized using descriptive statistics.

    Measured: 6 weeks

  3. Complete response rate (CRR)

    CRR is defined as the proportion of CIS patients who achieved CR at the Week 12 (3-month) Visit.

    Measured: 3 months

  4. Recurrence-free survival (RFS) rate

    RFS rate is defined as the proportion of patients with Ta/T1 disease who are recurrence-free at the Week 12 (3-month) Visit.

    Measured: 3 months

Secondary outcomes (12)

  1. Presence of anti-drug antibodies (ADA) in serum

    The number of patients with ADA will be summarized.

    Measured: 3 months

  2. UGN-301 maximum serum concentration (Cmax) following single and repeat dose administration

    Data will be summarized using descriptive statistics.

    Measured: 6 weeks

  3. UGN-301 area under the concentration-time curve (AUC) following single and repeat dose administration

    Data will be summarized using descriptive statistics.

    Measured: 6 weeks

  4. UGN-301 time to maximum serum concentration (tmax) following single and repeat dose administration

    Data will be summarized using descriptive statistics.

    Measured: 6 weeks

  5. UGN-301 terminal half-life (t1/2) following single and repeat dose administration

    Data will be summarized using descriptive statistics.

    Measured: 6 weeks

  6. UGN-301 concentration in serum at the end of a dosing interval (Ctau) following single and repeat dose administration

    Data will be summarized using descriptive statistics.

    Measured: 6 weeks

  7. Concentration of UGN-201 and its metabolites in blood and urine

    Data will be summarized using descriptive statistics.

    Measured: 6 weeks

  8. UGN-201 Cmax following single and repeat dose administration

    Data will be summarized using descriptive statistics.

    Measured: 6 weeks

  9. UGN-201 AUC following single and repeat dose administration

    Data will be summarized using descriptive statistics.

    Measured: 6 weeks

  10. UGN-201 tmax following single and repeat dose administration

    Data will be summarized using descriptive statistics.

    Measured: 6 weeks

  11. UGN-201 t1/2 following single and repeat dose administration

    Data will be summarized using descriptive statistics.

    Measured: 6 weeks

  12. UGN-201 Ctau following single and repeat dose administration

    Data will be summarized using descriptive statistics.

    Measured: 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2022
  2. Study start1 Jun 2022
  3. Primary completion9 Jan 2026
  4. Study completion9 Jan 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05375903
Sponsor's protocol ID
UR001
Status last verified
Jan 2026
First submitted
5 May 2022
Last updated
14 Jan 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing UGN-301, UGN-201 and Gemcitabine in people with Non-muscle Invasive Bladder Cancer and NMIBC, run by UroGen Pharma Ltd. at 13 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States, Italy, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs) (time frame: Up to 15 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05375903.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2026.

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