UGN-102 Yields Enduring 18-Month Responses in Low-Grade NMIBC

In patients with low-grade intermediate-risk non-muscle invasive bladder cancer who achieved a CR at 3 months with UGN-102, the 18-month DOR was 80.6%.

UGN-102 (mitomycin) demonstrated “compelling” duration of response (DOR) data in patients with low-grade, intermediate-risk non-muscle invasive bladder cancer who achieved a complete response (CR) at 3 months in the phase 3 ENVISION trial (NCT05243550), according to a press release from the developer, UroGen.¹

With a median follow-up of 18.7 months, the 18-month DOR was 80.6% (95% CI, 74.0%-85.7%) by Kaplan-Meier estimates; at 12 months, DOR was 82.5% (95% CI, 76.1%-87.3%).

Currently, UGN-102 is under review by the FDA in the indicated population, as they accepted a new drug application (NDA) in October 2024 and assigned a Prescription Drug User Fee Act date of June 13, 2025.²

Subgroup analysis results from the multinational, single-arm ENVISION trial were presented in a poster session at the 2025 ASCO Genitourinary Cancer Symposium (ASCO GU).³ They showed that, of patients with recurrent disease, 79.6% (95% CI, 73.9%-84.5%) achieved a CR at 3 months, and the estimated 12-month DOR rate was 82.3% (95% CI. 75.9%-87.1%).

“The progress with UGN-102 for low-grade intermediate-risk non-muscle invasive bladder cancer, including completion of the submission of our NDA ahead of schedule and compelling DOR data from the phase 3 ENVISION trial, further positions us to launch a product that we believe will represent a paradigm shift in care, if approved,” Liz Barrett, president and chief executive officer of UroGen, stated in the press release.¹ “UGN-102 is supported by a compelling body of clinical data, and we are very pleased to report today the 18-month DOR of 80.6% from the ENVISION trial, maintaining [DOR] consistent with 12-month DOR of 82.5% after a 3-month CR was achieved.”

The ENVISION trial evaluated the efficacy and safety of UGN-102 as the primary chemoablative therapy in those with recurrent low-grade intermediate-risk non-muscle invasive bladder cancer.⁴ A total of 240 patients were enrolled and received intravesical instillations of UGN-102 in the form of 75 mg of mitomycin via urinary catheter in an outpatient setting for 6 once-weekly instillations.

Eligibility criteria included disease histologically confirmed by cold cup biopsy at screening or within 8 weeks before screening; history of disease requiring treatment with transurethral resection of bladder tumors; intermediate-risk disease defined as presence of multiple tumors, a solitary tumor greater than 3 centimeters, or early or frequent recurrence; adequate organ function; a life expectancy of at least the trial’s duration; and negative voiding cytology for high-grade disease within 8 weeks of screening.⁴

History of high-grade bladder cancer; Bacillus Calmette-Guerin treatment for urothelial carcinoma within the previous year; known allergy or sensitivity to mitomycin; significant urethral stricture that precludes passage of a urethral catheter; current tumor grading of T1; concurrent upper tract urothelial carcinoma; and previous participation in a UGN-102 trial were among the reasons for study exclusion.

The trial’s primary end point was the CR rate at 3 months. Secondary end points included DOR of patients who achieved CR at 3 months, durable CR rate of patients who achieved CR at 3 months, disease-free survival in patients who achieved CR at 3 months, and safety.

A second poster shared at 2025 ASCO GU showed that, in patients with multiple and single tumors, the respective 3-month CR rates were 79.3% and 82.9%; the rates of recurrence at 15 months were 18.5% and 11.8%.⁵ Additionally, when tumor burden was 3 cm or less and greater than 3 cm, the 3-month CR rates were 82.8% and 73.2%, and 15.4% and 20.0%, respectively, experienced recurrence of low-grade disease, progression, or death by 15 months.

Regarding safety, previous analysis showed that treatment-emergent adverse effects (TEAEs) included dysuria (23.0%), hematuria (8.3%), urinary tract infection (7.1%), pollakiuria (6.7%), fatigue (5.4%), urinary retention (5.0%), urethral stenosis (4.6%), COVID-19 (3.8%), constipation (3.8%), nausea (3.8%), and micturition urgency (3.8%).⁶

“Treatment with UGN-102 resulted in a high, clinically meaningful CR rate in patients with [low grade intermediate-risk non-muscle invasive breast cancer],” lead study author Sandip M. Prasad, MD, of Morristown Medical Center, Atlantic Medical Group in New Jersey, and coauthors wrote in one of the presentations.⁵ “UGN-102 may represent a valuable treatment option for many patients with [low-grade intermediate-risk non-muscle invasive bladder cancer].”

References

1. UroGen Pharma reports fourth quarter and full year 2024 financial results and announces updated 18-month duration of response (DOR) of 80.6% from the phase 3 ENVISION trial of UGN-102. News release. UroGen Pharma Ltd. March 10, 2025. Accessed March 11, 2025. https://tinyurl.com/4wuxznn7
2. UroGen announces FDA acceptance of its new drug application for UGN-102. News release. UroGen Pharma Ltd. October 15, 2024. Accessed March 11, 2025. https://tinyurl.com/2ev5mk95
3. Prasad SM, Hu B, Bjurlin M, et al. Treatment of low-grade intermediate-risk non-muscle-invasive bladder cancer with UGN-102: results of the phase 3 ATLAS and ENVISION studies. J Clin Oncol. 2025;43(suppl 5):777. doi:10.1200/JCO.2025.43.5_suppl.777
4. A phase 3 single-arm study of UGN-102 for treatment of low-grade intermediate-risk non-muscle invasive bladder cancer (ENVISION). ClinicalTrials.gov. Updated November 4, 2024. Accessed March 11, 2025. https://tinyurl.com/r6wpd7bu
5. Prasad SM, Shishkov D, Mihaylov NV, et al. Impact of tumor burden and focality in recurrent low-grade intermediate-risk non-muscle invasive bladder cancer on response to treatment with UGN-102: a subanalysis of the phase 3 ENVISION trial. J Clin Oncol. 2025;43(suppl 5):776. doi:10.1200/JCO.2025.43.5_suppl.776
6. Prasad SM, Shishkov D, Mihaylov NV, et al. Primary chemoablation of recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer with UGN-102: a single-arm, open-label, phase 3 trial (ENVISION). J Urol. 2025;213(2):205-216. doi:10.1097/JU.0000000000004296