UGN-101 shows promising real-world chemo-ablative effect in UTUC

UGN-101 (Jelmyto) demonstrated similar rates of rendered disease free (RDF) among patients who underwent complete ablation, partial ablation, and biopsy only for low-grade upper tract urothelial carcinoma (LG-UTUC), according to findings from the first real-world sub-analysis of the mitomycin-containing reverse thermal gel.^1,2

For the study, 116 patients with low-grade UTUC were treated with UGN-101 across 15 high-volume centers.

The data were published in Urologic Oncology.

“Implementing Jelmyto earlier in real-world scenarios for LG-UTUC may offer appropriate low-risk patients the choice of minimal ablation or biopsy alone for renal preservation. This kidney-sparing approach aligns with the first-ever UTUC [American Urological Association]/[Society of Urologic Oncology] Guideline, which includes Jelmyto and strongly recommends tumor ablation as the initial management approach for low-grade favorable UTUC,” said lead author Hristos Z. Kaimakliotis, MD, in a news release on the findings. Kaimakliotis is an associate professor of urology at Indiana University Medical Center in Indianapolis.

For the study, 116 patients with low-grade UTUC and tumors that appeared to impede renal preservation were treated with UGN-101 across 15 high-volume centers. The primary end point was RDF rate upon initial ureteroscopy (URS) following treatment. RDF was defined as a “complete response or partial response with minimal mechanical ablation to endoscopically clear the upper tract of visible disease,” according to the authors.

In total, 50 renal units underwent complete ablation, 42 underwent partial ablation, and 20 underwent biopsy alone. Tumor size was less than 1 cm for complete ablation, 1 to 3 cm for partial ablation, and greater than 3 cm for biopsy alone.

At first URS following UGN-101, the data showed an RDF rate of 78.6% among those who underwent complete ablation, compared with an RDF rate of 57.6% among those who underwent partial ablation and 66.7% among those who received biopsy alone (P = .15). There was no significant impact of tumor size prior to induction on RDF rates (P = .17).

“The findings are encouraging and provide evidence in support of a new treatment strategy utilizing Jelmyto for reducing the volume of larger low-grade tumors to help spare the kidney,” said Chief Medical Officer of UroGen, Mark Schoenberg, MD, in the news release.

Further research into long-term outcomes with UGN-101 is being conducted in the prospective and retrospective uTRACT registry, which is currently enrolling participants.

Additional UGN-101 data from OLYMPUS

The phase 3 OLYMPUS trial (NCT02793128) was an open-label, single-arm, multicenter study assessing the safety and durability of response to UGN-101 in patients with low-grade UTUC.³

For the study, UGN-101 was administered to patients in 6 once-weekly instillations via retrograde catheter. In total, 71 patients initiated treatment. The primary end point was the number of patients who achieved a complete response by the end of treatment, defined as the complete absence of tumor as confirmed by a negative ureteroscopic evaluation, negative cytology, and negative for-cause biopsy.

Among all patients, 58% experienced a complete response to treatment. Of those, 56% remained in complete response after 12 months, including 50% of patients who did not receive any maintenance instillations and 59% of patients who had received at least 1 maintenance instillation.

In regard to safety, 44% of patients experienced ureteric stenosis, the most common treatment-emergent adverse event reported.

References

1. Kaimakliotis HZ, Tachibana I, Woldu S, et al. The ablative effect of mitomycin reverse thermal gel: Expanding the role for nephron preservation therapy in low grade upper tract urothelial carcinoma. Urol Oncol. Published online May 26, 2023. Accessed July 12, 2023. doi:10.1016/j.urolonc.2023.04.010

2. Retrospective study finds JELMYTO use effective following partial ablation or biopsy in larger volume low-grade upper tract urothelial tumors that impede kidney preservation. News release. UroGen Pharma. July 10, 2023. Accessed July 12, 2023. https://www.businesswire.com/news/home/20230710759851/en/Retrospective-Study-Finds-JELMYTO%C2%AE-Use-Effective-Following-Partial-Ablation-or-Biopsy-in-Larger-Volume-Low-Grade-Upper-Tract-Urothelial-Tumors-that-Impede-Kidney-Preservation

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