Investigational urothelial Ca Tx undergoing priority review by FDA

A novel gel formulation of mitomycin (UGN-101) is now undergoing priority review by the FDA for approval as a treatment for low-grade upper tract urothelial cancer (LG UTUC).

The New Drug Application (NDA) for UGN-101, which contains 4 mg of mitomycin-C per 1 mL of gel, is supported by the results from the phase III OLYMPUS (Optimized DeLivery of Mitomycin for Primary UTUC Study) clinical trial.

OLYMPUS investigator John L. Gore, MD, MS, of the University of Washington, Seattle, told Urology Times, “UGN-101 is a reverse hydrothermal gel formulation that solves one of the main problems we have trying to treat upper urinary tract tumors, and that is dwell time. A chemotherapy agent in solution might stay in the kidney for just 2 to 5 minutes, but with this sustained-release gel product, the exposure time to mitomycin in the renal pelvis and tumors can be several hours,” he said.

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“In the OLYMPUS trial, more than half of patients receiving the gel had complete regression of their cancers, and most of the responses were durable. Based on these results, if UGN-101 is approved, it can be strongly considered as a kidney-sparing option for a challenging cancer.”

The OLYMPUS trial had an open-label, single-arm design and enrolled 74 patients with pathologically confirmed non-invasive LG UTUC. They received six weekly instillations of UGN-101 administered via a standard ureteral catheter.

Body heat causes the instilled gel to solidify, allowing for prolonged contact of the mitomycin with the urothelium. The gel eventually degrades and is excreted.

The primary endpoint was complete response at 4 to 6 weeks after the last UGN-101 instillation. It was determined by visual assessment, upper tract washed urine cytology, and if there were remaining tumors, by biopsy or brush biopsy if technically feasible. Patients who achieved a complete response received monthly maintenance instillations of UGN-101 for up to 11 months.

Next:Complete response achieved in 59% of patients treated with UGN-101Complete response was achieved in 59% of patients treated with UGN-101. Based on follow-up of those patients, Kaplan Meier analysis estimated response durability was 89% at 6 months and 84% at 12 months, and estimated median time to recurrence was 13 months.

The most common treatment emergent adverse events were ureteric stenosis (43.7%), urinary tract infection (32.4%), hematuria (31.0%), flank pain (29.6%) nausea (23.9%), dysuria (21.1%), renal impairment (19.7%), and vomiting (19.7%).

“The safety profile of UGN-101 echoes the adverse event profile of intravesical mitomycin to treat bladder cancer with the addition that several patients in the OLYMPUS study developed ureteral strictures,” said Dr. Gore.

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“Most safety events were minor, although some of the ureteric strictures affected the ability to deliver continued maintenance instillations.”

Priority review of an NDA is granted by the FDA for medicines that are considered significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions. Priority review designation shortens the review period. The NDA for UGN-101 was accepted by the FDA and granted priority review in early December 2019 and was assigned a Prescription Drug User Fee Act action date of April 18, 2020.

Dr. Gore has received research funding from Ferring Pharmaceuticals, Inc.