UroGen Pharma Announces Promising Early Results from Phase 1 Study Evaluating UGN-301 for Non-Muscle Invasive Bladder Cancer
UroGen Pharma Ltd. (Nasdaq: URGN), a biotechnology company committed to developing and commercializing innovative therapies for urothelial and specialty cancers, today announced positive preliminary safety and clinical activity results from its ongoing Phase 1 dose-escalation study of UGN-301 (zalifrelimab) intravesical solution. This investigational therapy is being developed for the treatment of patients with recurrent non-muscle invasive bladder cancer (NMIBC), a disease known for its high recurrence rates and challenging management.
The Phase 1 trial was designed to assess the safety, tolerability, and optimal dosing of UGN-301 when administered locally into the bladder. UGN-301 is a CTLA-4 inhibitor delivered via UroGen’s proprietary reverse thermal gel (RTGel®) technology, which enables sustained exposure of the drug in the bladder while limiting systemic absorption. This novel approach is aimed at maximizing therapeutic benefits locally while reducing the systemic immune-related toxicities often associated with CTLA-4 checkpoint blockade therapies.
“The early safety profile and clinical activity data from this study are encouraging,” commented Dr. Jay Raman, Professor and Chair of Urology and Professor of Surgery at Penn State Cancer Institute. “The innovative approach of combining localized drug delivery with immune modulation represents a significant step forward in the treatment landscape for non-muscle invasive bladder cancer. These results merit further exploration in larger and more definitive clinical studies.”
Study Design and Safety Findings
The Phase 1 multi-part dose-escalation study enrolled up to 30 patients per treatment arm and was structured to determine the recommended Phase 2 dose (RP2D) of UGN-301 both as a monotherapy and in combination with other agents. In the monotherapy cohort, dose escalation continued up to the maximum feasible dose without encountering dose-limiting toxicities (DLTs). Importantly, no treatment-emergent adverse events (TEAEs) led to treatment discontinuation, further supporting the tolerability of UGN-301.
The trial’s data underscore the benefits of local delivery through the RTGel® technology, which solidifies at body temperature and allows for prolonged drug contact with the bladder lining. This innovative formulation helps achieve sustained exposure of zalifrelimab within the bladder while minimizing systemic drug levels. By restricting systemic exposure, UroGen aims to mitigate the risk of immune-related adverse events typically observed with systemic administration of checkpoint inhibitors, offering a potentially safer immunotherapy option for bladder cancer patients.
Clinical Activity Results
Early clinical activity signals were observed among the evaluable patients treated with UGN-301. Specifically, among patients with Ta/T1 disease — categories of NMIBC where the tumor has not invaded muscle tissue — 46% (6 out of 13) were recurrence-free at the 12-week evaluation. Additionally, among patients with carcinoma in situ (CIS) — a high-grade, flat, and aggressive form of bladder cancer — with or without concomitant Ta/T1 disease, 33% (2 out of 6) achieved a complete response at the same timepoint.
More notably, durability of response was observed in certain cohorts. Among patients with Ta/T1 disease treated with a 300 mg dose of UGN-301, 60% (3 out of 5) continued to remain recurrence-free at the 15-month disease assessment. This subgroup included a patient with high-grade T1 disease, suggesting that UGN-301 may have potential efficacy even in patients with more aggressive tumor features.
In the higher 500 mg dose cohort, although the sample size was small, durable responses were also observed. One out of four patients (25%) with CIS disease remained disease-free at six months, and one out of three patients (33%) with Ta/T1 disease similarly showed no evidence of disease at six months. Both of these patients continue to participate actively in the study, providing additional opportunities for long-term outcome assessment.
Future Directions and Combination Studies
The data presented thus far pertain only to the monotherapy arm of the study. UroGen plans to present results from the combination arms of the trial later this year. These arms are evaluating UGN-301 in conjunction with additional immunomodulatory or therapeutic agents, potentially enhancing efficacy by leveraging complementary mechanisms of action.
“Our hypothesis is that UGN-301’s unique formulation could potentially offer the dual benefits of maximizing therapeutic activity within the bladder while minimizing systemic side effects, which has historically been a major hurdle in cancer immunotherapy,” stated Dr. Mark Schoenberg, Chief Medical Officer at UroGen Pharma. “While these early results are promising, they require further validation through larger, randomized studies. Nevertheless, we are encouraged by the clinical activity observed to date and look forward to advancing UGN-301 as a potential new treatment option for patients with recurrent NMIBC.”
Dr. Schoenberg further emphasized that the company’s strategy is focused on addressing significant unmet needs in urothelial cancers, particularly for patients who may not respond adequately to existing therapies or who seek bladder-sparing treatment options.
Addressing an Unmet Need in Bladder Cancer Treatment
Bladder cancer remains one of the most common cancers worldwide, with NMIBC accounting for approximately 70–80% of newly diagnosed cases. While current treatment options such as intravesical Bacillus Calmette-Guérin (BCG) therapy are effective for some, many patients experience disease recurrence or progression, highlighting the need for innovative therapies with improved safety and efficacy profiles.
Checkpoint inhibitors targeting immune pathways such as PD-1, PD-L1, and CTLA-4 have transformed the management of many solid tumors, but their systemic use has been associated with significant immune-related toxicities. By delivering a checkpoint inhibitor directly to the bladder, UroGen aims to harness the power of immune activation while minimizing adverse effects — potentially offering patients a safer, yet effective, alternative.
If successful, UGN-301 could represent a paradigm shift in the management of NMIBC, offering a bladder-sparing option for patients who might otherwise face radical cystectomy, a surgery associated with significant morbidity and impact on quality of life.
The early results from UroGen Pharma’s Phase 1 study of UGN-301 are encouraging and lay the groundwork for continued clinical development. With a favorable safety profile, promising signs of clinical activity, and the innovative use of RTGel® technology for localized drug delivery, UGN-301 could emerge as a significant new option in the evolving landscape of bladder cancer therapy.
As the company prepares to report additional data later this year, including findings from combination therapy arms, the oncology community will be watching closely to see if UGN-301 can fulfill its potential as a groundbreaking treatment for patients with recurrent non-muscle invasive bladder cancer.
