OLYMPUS Study Results Show Clinical Benefit of UGN-101 in Low-Grade UTUC

Phillip Pierorazio, MD

Long-term follow-up data of the phase 3 OLYMPUS trial (NCT02793128) on the mitomycin-containing reverse thermal gel UGN-101(Jelmyto) revealed a median durability of response (DOR) of 28.9 months in adult patients with low-grade upper tract urothelial cancer (UTUC), according to UroGen Pharma Ltd.¹

The rollover study included patients with low-grade UTUC who completed OLYMPUS. At the data cutoff, data were available for 16 of 23 patients who had remained in a complete response (CR) at the end of the OLYMPUS study.

Along with a median DOR of 28.9 months (14.6-47.6 months) among the 16 patients, 13 remained in CR, and 2 had recurrence of low-grade UTUC which was on the same side as treated in OLYMPUS. Additionally, 1 patient underwent radical nephroureterectomy (RNU)to ureteral stricture without evidence of UTUC at the time of surgery and no patients progressed to high-grade disease.

“The clinical benefit of [UGN-101] was demonstrated in the phase 3 OLYMPUS study and data presented today highlighted the long-term durability of that benefit,” said Phillip Pierorazio, MD, chief, section of urology at Penn Presbyterian Medical Center, Philadelphia, Pennsylvania, in the press release. “[UGN-101] provides an effective and durable kidney-sparing treatment option and should be considered as primary therapy for adult patients with [low-grade] UTUC.”

In the multicenter, open-label, single-arm, phase 3, OLYMPUS study, investigators assessed the safety, tolerability, and tumor ablative effect of the UGN-101 in patients with low-grade UTUC.²

Patients were required to have at least 1 measurable papillary low-grade tumor, evaluated visually, ≤ 15 mm, at least 1 remaining papillary low-grade tumor evaluated visually with a diameter of at least 5 mm, and the absence of high-grade urothelial cancer that was diagnosed not more than 2 months prior to the screening. Patients with bilateral low-grade UTUC are eligible for enrollment if at least 1 side meets the inclusion criteria for the trial and if the other kidney does not require further treatments.

Once enrolled, patientswere treated once a week for a total of 6 times with installations of UGN-101 administered in a retrograde fashion. After 4-6 since the last installation, patients underwent a primary disease evaluation (PDE) to determine CR, which was the primary end point of the study. Other end points included long-term durability of CR, durability or CR, clinical benefit for patients with a partial response at the PDE visit, pharmacokinetics, and safety.

If patients achieved a CR at the PDE time point, they were eligible for the maintenance phase of the trial. Here, they could receive monthly maintenance treatment with UGN-101 for up to 12 months. Patients at the PDE time point were also assessed quarterly to determine the durability of response with the agent.

Findings from OLYMPUSshowed that the outcomes of interest, including DOR in patients who remain in CR at the end of the trial, events of disease recurrence and progression, post-study treatments and death, were promising.

Treatment with UGN-101 led to CRs in over 50% of patients with low-grade UTUC, each of which were maintained at 1 year. Then, 56.1% of patients who achieved a CR with the agent maintained that response at 12 months, which correlated to an 81.8% probability of maintaining a CR at the 12-month visit.

Regarding safety, ureteric stenosis was observed in 58% (n = 41) of patients receiving treatment with UGN-101. Further, only 17% (n = 12) of patients experienced a grade 3 event.

“[UGN-101] is an important addition to the urologist’s tool kit for treating LG-UTUC,” said Mark Schoenberg, MD, chief medical officer of UroGen, in the press release.. “These data are the first to show the potential for long-term recurrence free survival in patients treated with [UGN-101]. We look forward to additional independent validation of this important observation.”

_REFERENCES:

1. _{UroGen announces new data from the OLYMPUS trial that shows median durability of response of 28.9 months for JELMYTO®, the only non-surgical, chemoablative treatment for adults with low-grade upper tract urothelial cancer. News release. UroGen Pharma Ltd. December 1, 2022. Accessed December 6, 2022. https://bit.ly/3UQ4dWF}
2. _{The OLYMPUS study - optimized delivery of mitomycin for primary UTUC study (Olympus). ClinicalTrials.gov. Updated December 20, 2022. Accessed December 6, 2022. https://clinicaltrials.gov/ct2/show/NCT02793128}