Jelmyto demonstrates durable responses in low-grade UTUC in final OLYMPUS analysis

Complete responses (CRs) to mitomycin-containing reverse thermal gel (Jelmyto) proved to be durable in patients with low-grade upper tract urothelial carcinoma (UTUC), according to the final results of the pivotal phase 3 OLYMPUS trial presented during the 2020 Society of Urologic Oncology (SUO) Annual Meeting.¹

Data for a key study secondary outcome measure reported at SUO showed that 56.1% of patients who achieved a CR to Jelmyto maintained that response at 12 months. This translated to an 81.8% probability of maintaining a CR at the 12-month visit.

Of note, maintenance therapy was allowed by the study protocol; however, it was modified by study investigators and there was no evidence that maintenance treatment enhanced the durability of patient responses.

The durability data from the final analysis sustained the positive primary efficacy results from OLYMPUS.2 The primary data showed that 59.2% (n = 42) of the 71-patient ITT population achieved a CR. Eight patients had a partial response. Additionally, 20 (58.8%) of 34 patients considered unresectable at baseline by the treating urologist achieved a CR.

These primary data supported the April 2020 FDA approval of Jelmyto as the first therapy to treat patients with low-grade UTUC.

“[Jelmyto] is an innovative [treatment] and the first approved kidney-sparing approach for patients with low-grade UTUC, including for those whose tumors are difficult to treat endoscopically,” said presenting author Surena F. Matin, MD, The University of Texas MD Anderson Cancer Center in Houston, TX.

The open-label, single-arm, phase 3 OLYMPUS trial included patients from 24 academic centers in the United States and Israel. To be eligible for enrollment, adult patients had to have treatment-naïve or recurrent disease, ≥1 measurable papillary low-grade tumor ≤15 mm, and a wash urine cytology sampled from the pyelocaliceal system showing the absence of high-grade disease.

Patients received 6 once-weekly intravesical instillations with a retrograde catheter to the renal pelvis and calyces. Primary disease evaluation occurred 4 to 6 weeks following the completion of treatment. The study defined CR using 3 components: negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy.

Seventy-one patients received at least 1 dose of treatment. The most commonly occurring adverse events (AEs) were ureteric stenosis (44%), urinary tract infection (32%), hematuria (32%), flank pain (31%), and nausea (25%).

“Ureteric obstruction may be associated with an increasing number of doses/procedures,” said Matin. Ureteric stenosis was the most common obstruction event and was reported after a median of 6 instillations.

Matin said anecdotal reports from study investigators suggested that, “At initial development of ureteral narrowing, stricture formation might be mitigated by treatment holiday and steroid therapy.”

There were 5 patient deaths; however, none were determined by investigators to be related to the study treatment or study procedure. All deaths occurred at least 30 days following the final dose of study treatment.

References

1. Lerner S, Matin S, Kleinmann N, et al. Durability of response to chemoablative treatment of low-grade upper tract urothelial carcinoma with a mitomycin-containing reverse thermal hydrogel: Final results of the OLYMPUS trial. 2020 Society of Urologic Oncology Annual Meeting (virtual). December 3-5, 2020. Abstract 16.

2. Kleinmann N, Matin SF, Pierorazio PM, et al. Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial.Lancet Oncol. 2020;21(6):776-785.doi: 10.1016/S1470-2045(20)30147-9