UGN-101 demonstrates long-term durability in low-grade UTUC

Primary chemoablation with UGN-101 (Jelmyto), a mitomycin reverse thermal gel, demonstrated favorable long-term durability in patients with low-grade upper tract urothelial carcinoma (UTUC), according to long-term data from the phase 3 OLYMPUS trial (NCT02793128) published in The Journal of Urology.¹

The real-world use of UGN-101 is being explored in the JELMYTO uTRACT Registry.

UGN-101 was approved by the FDA in April 2020 based on data from this study.

In total, the OLYMPUS trial enrolled 71 patients, of whom 42 achieved a complete response following 6 weekly doses of UGN-101. Of those, 41 continued to be followed for 12 months following the initial response.

At a median follow-up of 28.1 months, the median duration of response (DOR) was 47.8 months (95% CI 13.0, not estimable) among those who achieved an initial complete response.

Additionally, at study completion, 49% of patients (n = 20) opted to undergo long-term follow-up for up to 5 years until disease recurrence, progression, or death. The median follow-up among these patients was 53.3 months. Of these, 75% showed no evidence of recurrence at last follow-up. The median DOR was not estimable due to a low event rate.

“The median DOR of 47.8 months in patients who achieved complete response with JELMYTO provides evidence of robust durability in maintaining control of low-grade UTUC over an extended period,” said lead author Phillip Pierorazio, MD, chief in the Section of Urology at Penn Presbyterian Medical Center and professor of surgery at the Hospital of the University of Pennsylvania in Philadelphia, Pennsylanvia, in a news release on the findings.² “The AUA/SUO recommend that urologists use kidney-sparing techniques as the preferred management strategy for patients with low-grade UTUC when possible. JELMYTO, with this evidence for extended durability of complete response, offers the opportunity for durable recurrence-free intervals.”

Previous data from the OLYMPUS trial showed that 56% of patients (23/41) remained in complete response at 12-month follow-up.³ Of those, 6 of 12 (50%) patients did not receive any maintenance instillations and 17 of 29 (59%) patients received at least 1. The estimated durability of response was 82% (95% CI, 66-91) at 12 months, per Kaplan-Meier.

Regarding safety, the most common treatment-emergent adverse event (TEAE) was ureteric stenosis, reported in 44% (31/71) of all patients in the study. A higher number of UGN-101 instillations was associated with an increased incidence of urinary TEAEs.

Overall, the prospective, open-label, single-arm OLYMPUS trial enrolled patients with low-grade UTUC to assess the efficacy, safety, and tolerability of UGN-101. Participants were enrolled across clinical trial sites in the United States and Isreal.⁴

Those enrolled in the study received 6 once weekly instillations of the therapy in a retrograde fashion. Those who achieved a complete response continued to receive UGN-101 once monthly for up to 11 instillations or until the first recurrence.

The primary end point was the number of patients who achieved a complete response at the end of treatment period. Secondary end points included the durability of complete response, clinical benefit for patients who achieved a partial response, and pharmacokinetic measures.

UGN-101 is continuing to be explored in the JELMYTO uTRACT Registry (NCT05874921) to obtain longitudinal real-world usage data in patients with UTUC. As of July, 191 patients have been enrolled across 19 sites. Enrollment for the registry remains ongoing, with a goal of enrolling 400 patients.⁵ 

References

1. Pierorazio PM, Kleinmann N, Shabsigh A, et al. Long-Term Outcomes of Primary Chemoablation of Low-Grade Upper Tract Urothelial Carcinoma (LG UTUC) with UGN-101, A Mitomycin Reverse Thermal Gel. J Urol. 2024:101097JU0000000000004331. doi:10.1097/JU.0000000000004331

2. New data from a long-term follow-up study to the OLYMPUS trial show median duration of response of four years in patients who achieved a complete response with JELMYTO. News release. UroGen Pharma Ltd. Published online and accessed November 26, 2024. https://investors.urogen.com/news-releases/news-release-details/new-data-long-term-follow-study-olympus-trial-show-median

3. Matin SF, Pierorazio PM, Kleinmann N, et al. Durability of response to primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel: OLYMPUS trial final report. J Urol. 2022;207(4):779-788. doi:10.1097/JU.0000000000002350

4. The OLYMPUS Study - Optimized DeLivery of Mitomycin for Primary UTUC Study (Olympus). ClinicalTrials.gov. Last updated December 22, 2020. Accessed November 26, 2024. https://clinicaltrials.gov/study/NCT02793128

5. uTRACT Jelmyto Registry: A registry of patients with upper tract urothelial cancer (UTUC) treated with Jelmyto (uTRACT). ClinicalTrials.gov. Last updated December 5, 2023. Accessed November 26, 2024. https://clinicaltrials.gov/study/NCT05874921