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

NCT05375903 | Completed Phase 1 FDA Drug

• 1 other identifier: UR001
• Study Type: interventional
• Target: 51
• Locations: 3 countries
• Sites: 13

Brief 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.

Conditions

Non-muscle Invasive Bladder Cancer; NMIBC; Carcinoma in Situ of Bladder; Bladder Cancer; Urothelial Carcinoma Bladder; Urothelial Carcinoma Recurrent

Outcome Measures

Primary Outcomes (4)

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

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

  Up to 15 months

• Concentration of UGN-301 in blood and urine

  Data will be summarized using descriptive statistics.

  6 weeks

• Complete response rate (CRR)

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

  3 months

• 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.

  3 months

Secondary Outcomes (12)

• Presence of anti-drug antibodies (ADA) in serum

  3 months

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

  6 weeks

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

  6 weeks

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

  6 weeks

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

  6 weeks

Study Arms (3)

UGN-301 monotherapy dose escalation (Arm A)

EXPERIMENTAL

Dose 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.

Drug: UGN-301

UGN-301 dose escalation + UGN-201 combination (Arm B)

EXPERIMENTAL

Dose 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.

Drug: UGN-301; Drug: UGN-201

UGN-301 dose escalation + gemcitabine combination (Arm C)

EXPERIMENTAL

Dose 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.

Drug: UGN-301; Drug: Gemcitabine

Interventions

UGN-301 DRUG

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).

Also known as: UGN-301 (zalifrelimab) intravesical solution

UGN-301 dose escalation + UGN-201 combination (Arm B); UGN-301 dose escalation + gemcitabine combination (Arm C); UGN-301 monotherapy dose escalation (Arm A)

UGN-201 DRUG

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).

Also known as: UGN-201 (imiquimod) intravesical solution

UGN-301 dose escalation + UGN-201 combination (Arm B)

Gemcitabine DRUG

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-301 dose escalation + gemcitabine combination (Arm C)

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• 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:

You may not qualify if:

• 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.
• Any medical psychological, familial, sociological, or geographical condition that, in the opinion of the Investigator, would preclude participation in the study.
• 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.

Sponsors & Collaborators

• UroGen Pharma Ltd.: lead

Study Sites (13)

Arkansas Urology

Little Rock, Arkansas, 72211, United States

Location

UCLA - University of California

Los Angeles, California, 90095, United States

Location

Florida Urology Partners, LLC

Tampa, Florida, 33615, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Manhattan Medical Research

New York, New York, 10016, United States

Location

Clinical Research Solutions

Middleburg Heights, Ohio, 44130, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

I.R.C.C.S. Ospedale San Raffaele

Milan, Italy

Location

National Tumor Institute Fondazione G. Pascale

Naples, Italy

Location

Istituto Oncologico Veneto

Padua, Italy

Location

NEXT Oncology IOB- Hospital Quironsalud Barcelona

Barcelona, 08023, Spain

Location

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

Barcelona, 08036, Spain

Location

NEXT Oncology- Hospital Quironsalud Mardrid

Madrid, 28223, Spain

Location

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms

Interventions

Imiquimod; Gemcitabine

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Sebastian Mirkin, MD

  UroGen Pharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2022
• First Posted: May 17, 2022
• Study Start: June 1, 2022
• Primary Completion: January 9, 2026
• Study Completion: January 9, 2026
• Last Updated: January 14, 2026

Record last verified: 2026-01

Locations

US (7); IT (3); ES (3)