UroGen Pharma Reports Positive Phase 1 Results for UGN-301 in Bladder Cancer

PRINCETON, NJ, USA, April 26, 2025 – UroGen Pharma Ltd. has released promising safety data from its Phase 1 dose-escalation trial of UGN-301 (zalifrelimab) intravesical solution, a drug under investigation for treating recurrent non-muscle invasive bladder cancer (NMIBC). UroGen, a biotech company, is focused on bringing innovative approaches to urothelial and specialty cancers. This recent study highlights the potential of UGN-301 as a targeted therapy with an acceptable safety profile.

According to Dr. Jay Raman, Professor and Chair of Urology at Penn State Cancer Institute, the initial safety and clinical activity results are encouraging. The innovative strategy of localized drug delivery paired with immune modulation could provide a novel approach to treating NMIBC.

The clinical trial was structured in multiple parts and involved up to 30 participants in each arm. The study aimed to evaluate the safety of UGN-301 and establish the recommended Phase 2 dosage, both as a single treatment and combined with other drugs. In the monotherapy section, the dose escalation was carried out to the highest feasible dose, without observing any dose-limiting toxicities or adverse events leading to discontinuation of treatment. The use of UGN-301 in UroGen’s proprietary reverse thermal gel (RTGel) ensured prolonged exposure of zalifrelimab in the bladder while keeping systemic exposure minimal. This approach reduces the risk of systemic immune-related toxicities commonly seen with CTLA-4 inhibition.

Clinically, the trial demonstrated promising results. Among the participants who received UGN-301, 46% of those with Ta/T1 disease and 33% of those with carcinoma in situ (CIS) ± Ta/T1 disease were free of recurrence or showed a complete response at the 12-week mark. Additionally, 60% of patients with Ta/T1 disease treated with a 300 mg dose remained recurrence-free at the 15-month assessment, including a patient with high-grade T1 disease. In the 500 mg group, 25% of patients with CIS and 33% of patients with Ta/T1 disease were disease-free at six months. These patients continue to participate in the study.

These outcomes underscore the potential of UGN-301 as a treatment option for NMIBC. The data from the combination arms of the study are expected to be presented later this year.

Mark Schoenberg, Chief Medical Officer at UroGen, expressed optimism about UGN-301’s unique formulation. The aim is to maximize therapeutic benefits while minimizing systemic side effects, a significant challenge in cancer immunotherapy. Although further clinical investigation is needed, the data so far is promising for patients with recurrent NMIBC.

Bladder cancer, the second most common urologic cancer in men in the U.S., primarily affects older populations. High-grade non-muscle invasive bladder cancer (HG-NMIBC) is a severe form of the disease that remains within the bladder’s inner layers but shows aggressive behavior. It accounts for about 30-40% of newly diagnosed NMIBC cases in the U.S. and poses a high risk of recurrence and progression, necessitating vigilant surveillance and intensive treatment. The standard treatment involves complete tumor resection followed by intravesical therapy such as Bacillus Calmette-Guérin (BCG). However, BCG has a 40-50% treatment failure rate, often leaving radical cystectomy as the only option. Given its high recurrence rate, HG-NMIBC presents substantial clinical challenges.

UGN-301, an anti-CTLA-4 monoclonal antibody licensed from Agenus Inc. in 2019, is formulated for intravesical administration to increase bladder drug concentrations without substantial systemic exposure. This formulation aims to reduce systemic toxicity associated with CTLA-4 blockade. UroGen is conducting a multi-arm Phase 1 study to evaluate UGN-301’s safety as monotherapy and in combination with other treatments for HG-NMIBC.