UGN-103 Shows Promise in Recurrent Low-Grade Bladder Cancer

Recurrent low-grade, intermediate-risk non–muscle invasive bladder cancer (LG-IR-NMIBC) presents an ongoing clinical challenge. Despite standard surgical management with transurethral resection of bladder tumor (TURBT), patients frequently experience disease recurrence, emphasizing the need for effective intravesical treatment options.

UGN-102 (Zusduri; UroGen Pharma Ltd), an intravesical mitomycin reverse thermal hydrogel, was previously approved by the FDA for adults with recurrent LG-IR-NMIBC. Its approval was based on results from the phase 3 ENVISION trial (NCT05243550), which demonstrated a complete response (CR) rate of approximately 80% at 3 months and an 82% probability of remaining in response at 12 months from initial CR.

Building on that foundation, UGN-103 was developed as a novel formulation designed to simplify drug preparation and shorten manufacturing time, while preserving the therapeutic profile of its predecessor.

UTOPIA Trial

UTOPIA (NCT06331299) is an ongoing, multicenter, single-arm phase 3 study evaluating UGN-103 as primary treatment for adults with recurrent LG-IR-NMIBC. Eligible patients received 6 once-weekly intravesical instillations of UGN-103 (mitomycin 75 mg in 56 mL admixture). Disease assessment was conducted 3 months after treatment initiation via cystoscopy, for-cause biopsy, and urine cytology. Patients with no detectable disease at that time entered a follow-up period with evaluations every 3 months, continuing until recurrence, progression, death, or completion of the 12-month follow-up window.

The primary end point was CR rate at 3 months, defined as no evidence of disease. Secondary end points included durability of response, safety and tolerability, and pharmacokinetics.

Patients Achieve a CR of 78%

A total of 99 patients received at least 1 instillation of UGN-103, with 97% completing all 6 instillations—reflecting strong treatment adherence. The median patient age was approximately 71 years, with 78% of patients aged 65 or older. The cohort was predominantly male (72%) and White (99%). Most patients (90%) presented with multiple tumors; in 96% of cases, the largest tumor diameter was 3 cm or less.

At the 3-month assessment, 77 of 99 patients in the intent-to-treat population achieved a CR, yielding an approximate 78% rate (95% CI, 68%-86%). Among nonresponders, 16% had residual disease and 4% progressed to high-grade disease. Two patients had missing or indeterminate responses.

UGN-103 Shows Favorable Safety Profile

Treatment-emergent adverse events (TEAEs) were reported in 60% of patients. Dysuria was the most common, occurring in 10% or more of patients (19%). Serious TEAEs were reported in 2 patients and included atrial fibrillation, osteoarthritis, and respiratory failure, none of which were considered treatment-related. No TEAEs resulted in death.

Clinical Conclusions

Results from the UTOPIA trial indicate that UGN-103 demonstrates a safety and efficacy profile comparable to that of UGN-102, with a CR rate of 78% and a favorable tolerability profile. These findings support continued investigation of UGN-103 as a viable intravesical treatment option for patients with recurrent LG-IR-NMIBC.

REFERENCE

Srivastava A, Vjaters E, Kaimakliotis HZ, et al. UTOPIA: a phase 3 trial of UGN-103, an intravesical mitomycin reverse thermal hydrogel, in recurrent low-grade intermediate-risk non-muscle invasive bladder cancer. Presented at: 2026 American Society of Clinical Oncology Annual Meeting; May 29-June 2, 2026; Chicago, IL. Abstract 4604.