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.

4604 Background: Management of recurrent low-grade (LG), intermediate-risk (IR) non-muscle invasive bladder cancer (NMIBC) remains challenging due to frequent recurrence following standard surgical management with transurethral resection of bladder tumor (TURBT). UGN-102 is an intravesical mitomycin reverse thermal hydrogel, approved by the Food and Drug Administration for treatment of adults with recurrent LG-IR-NMIBC based on the Phase 3 ENVISION trial demonstrating a complete response (CR) rate of 80% (95% confidence interval [CI]: 74, 85) at 3 months, with an 82% (95% CI: 76, 87) probability of remaining in response 12 months from initial CR. UGN-103 is a novel formulation of UGN-102 developed to simplify drug preparation and shorten manufacturing time. Methods: 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 provided written informed consent and received six once-weekly intravesical instillations of UGN-103 (mitomycin 75 mg in 56 mL admixture). Disease assessment was performed 3 months after start of treatment. Patients with no detectable disease entered a follow-up period, with evaluations every 3 months until recurrence, progression, death, or completion of follow-up (12 months after the 3-month visit). The primary endpoint was CR rate (defined as the proportion of patients assessed as having no evidence of disease at the 3-month visit) based on cystoscopy, for-cause biopsy, and urine cytology. Secondary endpoints include durability of response, safety and tolerability, and pharmacokinetics. Data cut off: September 3, 2025. Results: A total of 99 patients received ≥1 instillation of UGN-103; of these, 97% (n=96) received all 6 instillations. At baseline, median patient age was 71 years (range 46, 93), with 78% (n=77) being ≥65 years old. Most patients were male (72%; n=71) and 99% (n=98) were White. Most patients had multiple tumors (90%; n=87), with the longest tumor diameter being ≤3 cm in 96% (n=93). At 3 months, 77 of 99 patients in the intent-to-treat population achieved CR (CR rate: 78% [95% CI: 68, 86]). Non-CR outcomes included residual disease in 16% (n=16) and progression to high-grade disease in 4% (n=4). Two (2%) patients had missing/indeterminate responses. Treatment-emergent adverse events (TEAEs) were reported in 60% of patients (n=59), with the most common TEAE (≥10%) being dysuria (19%; n=19). Two (2%) patients had a total of 3 serious TEAEs, including atrial fibrillation, osteoarthritis, and respiratory failure; none were treatment related. No TEAE led to death. Conclusions: UGN-103 demonstrated a safety and efficacy profile similar to that observed with UGN-102 in patients with recurrent LG-IR-NMIBC, supporting continued evaluation of UGN-103 as an intravesical treatment option. Clinical trial information: NCT06331299 .