UGN-101 Shows Durable Responses in Urothelial Cancer in 5-Year Follow-Up

Five-year follow-up findings from the phase 3 OLYMPUS trial (NCT02793128) indicate that UGN-101 (mitomycin gel; Jelmyto) can provide durable disease control for adults with low-grade upper tract urothelial carcinoma (LG-UTUC) who achieve a complete response following primary chemoablation.¹

The findings, published in Therapeutic Advances in Urology, provide additional evidence of the durability of responses to UGN-101, a kidney-sparing treatment option for patients with LG-UTUC. Among 41 patients who achieved a complete response after treatment in OLYMPUS, the median duration of response was 47.8 months, with a median follow-up of 28.1 months (95% CI, 13.1-60.1).

A subset of 20 patients entered the long-term follow-up study, with a median follow-up of 53.3 months (95% CI, 27.9-72.8). In this subset, the median duration of response was not estimable (95% CI, 43.5 months to not estimable), reflecting the low number of events. As of March 2025, 15 of 20 patients (75%) in the long-term follow-up cohort remained event-free. No progression to high-grade disease was reported during extended follow-up.

"These [5]-year findings further demonstrate the long-term durability of response achieved with [UGN-101] in adults with [LG-UTUC]," Phillip Pierorazio, MD, chief of urology at Penn Presbyterian Medical Center, professor of surgery at the Hospital of the University of Pennsylvania, and lead author, stated in a news release. "The sustained disease control observed during extended follow-up provides additional evidence supporting the long-term benefits of [UGN-101]."

OLYMPUS Study Design and Long-Term Outcomes

OLYMPUS was an open-label, single-arm, multicenter phase 3 trial evaluating UGN-101 as primary chemoablation for adults with primary or recurrent LG-UTUC. The study enrolled 74 patients, of whom 71 received at least 1 dose of treatment.³ Patients received 6 once-weekly instillations of UGN-101, administered into the renal pelvis and calyces through a retrograde catheter. Patients who achieved a complete response after induction therapy could receive up to 11 monthly maintenance instillations.

In the initial trial, 42 of 71 treated patients (59%) achieved a complete response 4 to 6 weeks after treatment. Complete response was defined by negative ureteroscopic evaluation, negative cytology, and a negative biopsy when performed for clinical indication. Of these patients, 41 were followed for response durability and were eligible for the subsequent long-term analysis if they met the study criteria.

The extended follow-up findings build on earlier OLYMPUS results by examining response duration among patients who initially responded to treatment. Because the long-term cohort included only 20 patients who achieved a complete response and entered extended follow-up, the findings do not represent outcomes for all patients who received UGN-101. The single-arm design also limits comparisons with other treatment approaches.

Treatment Considerations

UGN-101, approved in 2020, is a reverse thermal hydrogel formulation containing 4 mg of mitomycin per mL. The solution is liquid when cooled and becomes a semisolid gel at body temperature, allowing the drug to remain in the upper urinary tract for approximately 4 to 6 hours before dissolving and clearing through normal urine flow. The treatment is approved for adults with LG-UTUC and can be administered retrograde through a ureteral catheter or antegrade through a nephrostomy tube.

The kidney-sparing approach may be relevant for patients seeking an alternative to surgery that removes the kidney and ureter. However, treatment-related risks remain important when weighing this approach. In the original OLYMPUS trial, ureteric stenosis was reported in 31 of 71 treated patients (44%), making it the most frequently reported adverse event. Urinary tract infections occurred in 23 patients (32%), and hematuria occurred in 22 (31%).

The 5-year findings support continued assessment of response durability after UGN-101 treatment. The small long-term cohort and selection of patients who initially achieved a complete response should be considered when interpreting the results in clinical practice.

REFERENCES

1. Pierorazio PM, Hu B, Raman JD, et al. Five-year outcomes following primary chemoablation with UGN-101 in low-grade upper tract urothelial carcinoma: Evidence of durable complete response from an observational long-term follow-up of the phase 3 Olympus trial. Therapeutic Advances in Urology. 2026;18. doi:10.1177/17562872261493697

2. UroGen’s Final Results from Olympus Five-Year Follow-Up Study Reinforces Durable Response with JELMYTO in Patients with Low-Grade Upper Tract Urothelial Cancer. News release. UroGen. October 28, 2026. Accessed October 29, 2026. https://tinyurl.com/2wb6sx4m

3. The OLYMPUS Study - Optimized DeLivery of Mitomycin for Primary UTUC Study (Olympus). ClinicalTrials.gov. Updated December 22, 2020. Accessed October 29, 2026. https://clinicaltrials.gov/study/NCT02793128