What side effects are associated with this type of intervention?

Common treatments for bladder cancer, particularly those involving immune checkpoint inhibitors like CTLA-4 inhibitors (e.g., UGN-301 or Zalifrelimab), PD-1 inhibitors (e.g., pembrolizumab, nivolumab), and traditional chemotherapy, have various side effects. Immune checkpoint inhibitors can cause immune-related adverse events such as skin reactions, endocrine disorders, and gastrointestinal symptoms. Traditional chemotherapy often leads to side effects like nausea, fatigue, and increased risk of infections. Specific to CTLA-4 inhibitors, patients may experience immune-mediated side effects including colitis, hepatitis, and dermatitis.

What prior FDA approvals exist?

The FDA has approved several immune checkpoint inhibitors for the treatment of bladder cancer. Notably, Atezolizumab and Pembrolizumab, which target PD-L1 and PD-1 respectively, have been approved for patients with locally advanced or metastatic urothelial carcinoma. While Tremelimumab, another CTLA-4 inhibitor like UGN-301, has shown clinical activity in urothelial carcinoma, it has not yet received FDA approval specifically for bladder cancer. These approvals highlight the growing role of immunotherapy in treating bladder cancer, with ongoing studies like the one involving UGN-301 aiming to expand these options.

What other types of research exist?

Promising novel alternatives to UGN-301 (Zalifrelimab) for bladder cancer patients include: 1) Pembrolizumab (Keytruda) - a PD-1 inhibitor, which has shown efficacy in various stages of bladder cancer. 2) Atezolizumab (Tecentriq) - a PD-L1 inhibitor, used for patients ineligible for cisplatin-based chemotherapy. 3) Enfortumab vedotin (Padcev) - an antibody-drug conjugate targeting Nectin-4, approved for advanced urothelial carcinoma. 4) Erdafitinib (Balversa) - an FGFR inhibitor for patients with specific FGFR genetic alterations. These treatments offer different mechanisms of action and have shown promising results in clinical trials.

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Monoclonal Antibodies

UGN-301 for Bladder Cancer

Phase 1

Recruiting

Research Sponsored by UroGen Pharma Ltd.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Arm A: Have confirmed recurrent NMIBC with HG Ta disease and/or CIS or recurrent IR LG Ta disease.

Patients with HG Ta 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 disease within 12 months of completion of adequate BCG therapy, or 2) recurrent HG Ta disease within 6 months of completion of adequate BCG therapy. Notes: Adequate BCG therapy is defined as at least 5 of 6 doses of an initial induction course plus at least 2 of 3 doses of maintenance therapy or 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.

Must not have

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.

Timeline

Screening 7 days

Treatment 6 weeks

Follow Up 12 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests UGN-301, a drug delivered directly into the bladder, alone or with other drugs. It targets patients with a specific type of recurrent bladder cancer. The goal is to find the safest and most effective dose by adjusting based on early findings.

Who is the study for?

This trial is for adults with recurrent non-muscle invasive bladder cancer who have tried BCG therapy without success and are not candidates for or willing to undergo radical cystectomy. They should expect to live more than a year, have no muscle-invasive or metastatic cancer, and be free of certain other cancers in the last five years. Participants must also have proper organ function, not be pregnant or nursing, use effective birth control if applicable, and cannot have autoimmune diseases requiring treatment within the past two years.

What is being tested?

The study tests UGN-301 (zalifrelimab), alone or with other agents, administered directly into the bladder to determine its safety and optimal dose for Phase 2 trials in patients whose bladder cancer has come back after previous treatments. It's an early-stage trial where doses increase gradually to find out how much can be given safely.

What are the potential side effects?

While specific side effects of UGN-301 aren't listed as it's a new treatment under investigation, similar therapies often cause irritation at the administration site (bladder), potential allergic reactions, flu-like symptoms such as fever and chills, fatigue, urinary issues like discomfort during urination or increased frequency.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have a confirmed case of recurrent bladder cancer.

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My bladder cancer has not responded to BCG treatment and I cannot or do not want to have my bladder removed.

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I cannot tolerate a full course of BCG treatment.

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My bladder cancer is less than 3 cm and treatments before didn’t work.

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I can take care of myself and am up and about more than half of my waking hours.

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I don't have cancer in my upper urinary tract or prostate area.

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I am a man who is either surgically sterile or willing to use two effective birth control methods during and for a month after the study.

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My recent blood tests meet the required levels for treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My bladder cancer has spread deeply or to other parts of my body.

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I am currently receiving treatment for bladder cancer.

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My cancer is classified as T1.

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I have been treated with specific immune system drugs before.

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I am not pregnant or nursing.

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I cannot tolerate treatments directly into my bladder or bladder surgery.

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I have not had bladder treatments within the last 4 weeks.

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I haven't taken immune therapy recently.

Timeline

Screening ~ 7 days1 visit

Treatment ~ 6 weeks8 visits

Follow Up ~ 12 months4 visits

Screening ~ 7 days

Treatment ~ 6 weeks

Follow Up ~12 months

This trial's timeline: 7 days for screening, 6 weeks for treatment, and 12 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Complete response rate (CRR)

Concentration of UGN-301 in blood and urine

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

+1 more

Secondary study objectives

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

Presence of anti-drug antibodies (ADA) in serum

UGN-201 AUC following single and repeat dose administration

+9 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: UGN-301 monotherapy dose escalation (Arm A)Experimental Treatment1 Intervention

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.

Group II: UGN-301 dose escalation + gemcitabine combination (Arm C)Experimental Treatment2 Interventions

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.

Group III: UGN-301 dose escalation + UGN-201 combination (Arm B)Experimental Treatment2 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Gemcitabine

2017

Completed Phase 3

~1920

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Bladder cancer treatments often include immunotherapy, chemotherapy, and targeted therapies. Immunotherapy, such as CTLA-4 inhibitors like Zalifrelimab, works by blocking immune checkpoints that cancer cells use to evade the immune system, thereby enhancing the body's ability to fight cancer. This is particularly important for bladder cancer patients as it offers a treatment option that can potentially lead to durable responses and long-term survival. Chemotherapy targets rapidly dividing cells, including cancer cells, but can also affect normal cells, leading to side effects. Targeted therapies aim at specific molecular pathways involved in cancer growth and spread, offering a more precise treatment approach. Understanding these mechanisms helps patients and doctors choose the most effective treatment strategy based on the cancer's characteristics and the patient's overall health.

Rationale and Outcomes for Neoadjuvant Immunotherapy in Urothelial Carcinoma of the Bladder.[Mechanism of action of intravesical BCG. Biological bases and clinical applicability.][The role of immunotherapy in the modern treatment of urothelial carcinoma].