UGN-301 for Bladder Cancer

Not currently recruiting at 13 trial locations

Overseen By Christine Lentowski

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 1

Sponsor: UroGen Pharma Ltd.

Must not be taking: CTLA-4 inhibitors, PD-1 inhibitors

Disqualifiers: Muscle invasive cancer, Active infection, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests UGN-301, a new treatment for bladder cancer, specifically targeting non-muscle invasive bladder cancer (NMIBC) that recurs. The goal is to assess the safety of UGN-301 and determine the best dose for future studies. Participants will receive UGN-301 alone or in combination with other treatments like UGN-201 or gemcitabine. This trial suits those whose NMIBC has returned after treatments, especially if their cancer did not respond well to past therapies like BCG, or if they cannot or do not wish to have their bladder removed. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had intravesical therapy within 4 weeks before starting the study treatment, and you must not be on current systemic therapy for bladder cancer. It's best to discuss your specific medications with the study team.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on current systemic therapy for bladder cancer or have had certain immune therapies recently. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that UGN-301, also known as zalifrelimab, is generally safe for patients. Most side effects in studies were mild or moderate, meaning they were not too severe and could be managed easily. Importantly, no serious side effects prevented dose increases.

For those taking UGN-301 with UGN-201 or gemcitabine, safety remained good. Mild to moderate side effects were the most common, and no serious problems halted the treatments. Overall, early studies suggest that UGN-301, whether used alone or with other drugs, appears safe for patients so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about UGN-301 for bladder cancer because it offers a novel approach compared to standard treatments like BCG therapy and chemotherapy. UGN-301 is an innovative immune checkpoint inhibitor targeting CTLA-4, which helps unleash the body's immune system to attack cancer cells more effectively. Additionally, the combination arms with UGN-201 and gemcitabine could enhance immune response and improve treatment outcomes. These new strategies have the potential to offer better efficacy and safety profiles for patients with non-muscle invasive bladder cancer.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research shows that UGN-301, also known as zalifrelimab, may help treat a type of bladder cancer that recurs but does not invade muscle. Early results suggest it is generally safe, with mostly mild to moderate side effects. In this trial, participants may receive UGN-301 as a monotherapy or in combination with UGN-201 or gemcitabine to determine if these combinations can lead to better outcomes. Although specific efficacy data is not yet available, early studies on its safety are promising. This positions UGN-301 as a potential new option for patients with this type of bladder cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Sunil Raju, MBBS

Principal Investigator

UroGen Pharma

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

I am using or willing to use two effective birth control methods during and for 1 month after treatment, or I am not able to have children.

I cannot tolerate a full course of BCG treatment.

Exclusion Criteria

You have taken part in a study testing a new medication or device in the past 4 weeks.

I have not received any vaccines in the last 2 weeks.

I haven't had cancer in other organs except skin cancer or specific urinary cancers in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Period

Eligible patients enter a 12-week induction period to receive UGN-301 as monotherapy or in combination with other agents

12 weeks

Safety Follow-up

Patients with noninvasive papillary carcinoma and/or tumor that invades the lamina propria who do not have disease recurrence and patients with carcinoma in situ who have a complete response at 3 months will return for a safety follow-up visit

6 months

Optional Maintenance Period

Ta/T1 patients without disease recurrence and CIS patients with complete response at 6 months may enter an optional maintenance period

up to 9 months

What Are the Treatments Tested in This Trial?

Interventions

• Zalifrelimab (UGN-301)

Trial Overview 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.

How Is the Trial Designed?

Group I: UGN-301 monotherapy dose escalation (Arm A) Experimental Treatment 1 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 Treatment 2 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 Treatment 2 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.

Who Is Running the Clinical Trial?

UroGen Pharma Ltd.

Lead Sponsor

Trials

20

Recruited

1,400+

Published Research Related to This Trial

Atezolizumab, an anti-PD-L1 therapy, showed long-term safety and efficacy in patients with metastatic urothelial carcinoma, with a median follow-up of 37.8 months and a low incidence of severe treatment-related adverse events (9%).

The treatment resulted in a 26% objective response rate, with a median duration of response of 22.1 months, and median overall survival of 10.1 months, particularly benefiting patients with higher PD-L1 expression on immune cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study. Petrylak, DP., Powles, T., Bellmunt, J., et al.[2022]

Whole-exome sequencing of tumor samples from 88 advanced bladder cancer patients revealed genetic factors, such as ARID1A mutations and tumor mutational burden, that correlate with improved survival outcomes after immune checkpoint blockade (ICB) therapy.

The study identified four distinct molecular subtypes of bladder cancer that show different sensitivities to ICB, which were validated in an independent cohort, suggesting that these subtypes can help tailor treatment strategies for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Genetic Subtypes of Urothelial Carcinoma With Differential Outcomes on Immune Checkpoint Blockade. Sarfaty, M., Golkaram, M., Funt, SA., et al.[2023]

In a phase 2 trial involving 310 patients with metastatic urothelial carcinoma who had previously failed platinum-based chemotherapy, treatment with atezolizumab resulted in a significant overall response rate of 15%, which is notably higher than the historical control rate of 10%.

Atezolizumab demonstrated good tolerability, with only 16% of patients experiencing grade 3-4 treatment-related adverse events, and no treatment-related deaths, indicating it is a safe option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Rosenberg, JE., Hoffman-Censits, J., Powles, T., et al.[2022]

In a study of 115 patients with metastatic urothelial carcinoma treated with atezolizumab (ATZ) after failing first-line chemotherapy, the objective response rate was 28.7%, indicating that ATZ is effective in this patient population.

The treatment was well tolerated, with 98% of patients experiencing adverse events, but only 21.2% had severe (grade 3-4) treatment-related adverse events, suggesting a manageable safety profile similar to previous clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. Tural, D., Ölmez, ÖF., Sümbül, AT., et al.[2022]

The combination of gemcitabine and irinotecan (Irinogem) showed promising efficacy in treating metastatic bladder cancer, with 8 out of 13 evaluable patients achieving an objective response, including 2 complete responses and 6 partial responses, and a median progression-free survival of 8.78 months.

The treatment was associated with manageable toxicity, with no toxic deaths reported, although some patients experienced significant side effects like neutropenia and diarrhea. However, the study's early closure due to funding issues limits the ability to draw definitive conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of gemcitabine and irinotecan in patients with locally advanced or metastatic bladder cancer. Chaudhary, UB., Verma, N., Keane, T., et al.[2022]

Five anti-PD-1/PD-L1 monoclonal antibodies have been approved by the FDA for treating advanced or metastatic urothelial carcinoma (UC) after first-line chemotherapy failure, highlighting a new treatment avenue for these patients.

The review details the mechanisms of action, clinical efficacy, recommended usage, and potential adverse events of these immune checkpoint inhibitors, emphasizing their role in improving treatment options for UC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comprehensive Review of US FDA-Approved Immune Checkpoint Inhibitors in Urothelial Carcinoma. Hsu, FS., Su, CH., Huang, KH.[2018]

In a study of 77 patients with advanced urothelial cell carcinoma (UCC) who had previously failed platinum-based therapy, vinflunine showed an overall response rate of 23.4% and a median overall survival of 7.7 months, indicating its efficacy in this patient population.

The treatment was associated with manageable safety concerns, with grade 3/4 toxicities occurring in a minority of patients, including leucopenia (16.9%) and anemia (6.5%), suggesting that vinflunine can be a viable option for patients in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinflunine in routine clinical practice for the treatment of advanced or metastatic urothelial cell carcinoma - data from a prospective, multicenter experience. Retz, M., de Geeter, P., Goebell, PJ., et al.[2022]

Recent studies have shown that immunotherapy agents targeting PD-1 and PD-L1, such as atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab, are effective and have manageable side effects for patients with metastatic urothelial carcinoma who have progressed after platinum-based chemotherapy.

These therapies may offer an overall survival advantage, particularly in patients with PD-L1-positive tumors, highlighting the need for better biomarkers to identify which patients will benefit most from these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Emerging Role of PD-1/PD-L1-Targeting Immunotherapy in the Treatment of Metastatic Urothelial Carcinoma. Gwynn, ME., DeRemer, DL.[2018]

Atezolizumab has been approved by the FDA as a treatment for advanced bladder cancer, specifically for patients who cannot receive cisplatin chemotherapy.

This approval provides a potentially more effective treatment option compared to carboplatin-based chemotherapy, particularly for frail and elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nod for Atezolizumab in Advanced Bladder Cancer. [2018]

In a study of 118 patients with advanced urothelial carcinoma treated with PD-1 inhibitors, 95% experienced adverse events (AEs), with 88% being mild (grade 1-2) and 51% being severe (grade 3-4), but no treatment-related deaths occurred.

Combination therapy with PD-1 inhibitors and chemotherapy resulted in better disease control (78% vs. 43% for monotherapy) but also significantly increased the incidence of severe AEs (89% vs. 32%), indicating that while effective, this approach requires careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Adverse Events of PD-1 Inhibitors in Patients With Advanced Urothelial Carcinoma From a Real-World Experience. Sun, F., Wang, D., Liu, A., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1078143924009165

133 a phase 1 dose-escalation study of ugn-301 ... A phase 1 study (UR001) was initiated to evaluate the safety and determine the recommended phase 2 dose (RP2D) of UGN-301 as monotherapy and in combination ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05375903

A Phase 1 Dose-escalation Study of UGN-301 in Patients ... This study is being conducted to evaluate the safety and determine the recommended Phase 2 dose (RP2D) of UGN-301 (zalifrelimab) administered intravesically as ...

3. onclive.com onclive.com/view/ugn-301-shows-early-tolerability-in-recurrent-non-muscle-invasive-bladder-cancer

UGN-301 Shows Early Tolerability in Recurrent ... - OncLive UGN-301 showed a favorable safety profile with mostly mild or moderate treatment-emergent adverse effects and no dose-limiting toxicities in ...

4. urotoday.com urotoday.com/conference-highlights/suo-2024/suo-2024-bladder-cancer/156750-suo-2024-a-phase-i-dose-escalation-study-of-ugn-301-zalifrelimab-as-monotherapy-and-in-combination-with-other-agents-in-patients-with-recurrent-non-muscle-invasive-bladder-cancer.html

SUO 2024: A Phase I Dose-Escalation Study of UGN-301 ... Approximately 15–30% of patients with high-grade NMIBC and over 50% of patients with intermediate-risk disease experience disease recurrence or ...

5. auajournals.org auajournals.org/doi/pdf/10.1097/01.JU.0001109740.05294.af.34

treatment of recurrent non-muscle invasive bladder cancer ... UGN-301 was well tolerated at all dose levels with a favorable safety profile. Evaluation of UGN-301 in combination with UGN-201 (Arm B) and gemcitabine (Arm C) ...

6. auajournals.org auajournals.org/doi/10.1097/01.JU.0001109740.05294.af.34

RESULTS OF A PHASE 1 DOSE-ESCALATION STUDY UGN-301 was well tolerated at all dose levels with a favorable safety profile. Evaluation of UGN-301 in combination with UGN-201 (Arm B) and ...

7. investors.urogen.com investors.urogen.com/news-releases/news-release-details/urogen-pharma-announces-encouraging-results-phase-1-dose

We strive to put patients first and preserve their future ... In the 500 mg cohort, 25% (1 of 4) of patients with CIS disease and 33% (1 of 3) of patients with Ta/T1 disease remained disease-free at six ...