An evaluation of UGN-101, a sustained-release hydrogel polymer-based formulation containing mitomycin-C, for the treatment of upper urothelial carcinomas

ABSTRACT

Introduction

The treatment of low-grade upper tract urothelial carcinomas (UTUCs) after either surgery, or nephron-sparing techniques remains an unmet need in Genitourinary (GU) Oncology. UGN-101 is a novel drug in development for the treatment of UTUCs; it is composed of a sustained-release hydrogel polymer-based formulation containing the antitumor antibiotic mitomycin-C (MM-C); cold UGN-101 is liquid, but at body temperature, it becomes a gel, and thus, when administered through a ureteral catheter, it sticks to the upper tract urothelium, slowly releasing MM-C.

Areas covered

Here, the authors review the preclinical rationale for the development of UGN-101, as well as presently available clinical results for the treatment of low-grade UTUCs.

Expert opinion

The positive results of the recently completed OLYMPUS trial suggest the feasibility, activity (59% of complete responses, with just 6 of these complete responders on follow-up who recurred), and safety (68% of patients experiencing mild to moderate urinary adverse events) of UGN-101 instillations into the upper urinary tract. Our expectations are that UGN-101 will soon become a standard of treatment for low-grade UTUC at risk of relapse after either surgery, or nephron-sparing techniques.

KEYWORDS:

• UGN-101
• RTGel
• mitomycin-C
• upper tract urothelial carcinoma
• Olympus trial

Article highlights

• The treatment of low-grade upper tract urothelial carcinomas (UTUCs) after either surgery, or nephron-sparing techniques remains an unmet need

• UGN-101 is a novel drug composed of a sustained-release hydrogel polymer-based formulation containing mitomycin-C (MM-C); cold UGN-101 is liquid, but at body temperature, it becomes a gel, and thus, when administered through a ureteral catheter, it sticks to the upper tract urothelium, slowly releasing MM-C

• In the animal model, UGN-101 proved to be a safe and effective method to deliver MM-C in the upper urinary tract

• The Olympus trial was a prospective, open-label, single-arm trial, aimed at assessing the efficacy, safety, and tolerability of UGN-101 when instilled in the upper urinary tract of patients with a primary noninvasive, endoscopically unresectable, low-grade, UTUC

• The Olympus study succeeded, since of the 71 patients who received at least one instillation, 42 (59%) achieved a CR, defined as both a negative ureteroscopic evaluation and a negative cytology; furthermore, of the 41 patients who entered the follow-up period, only 6 (15%) recurred; notably, none of them progressed to high-grade or invasive cancer

• The most common adverse events evidenced included ureteral stenosis, urinary tract infection, hematuria, flank pain, dysuria, transient creatinine increase, hydronephrosis, and frequency; they were usually transient and mild to moderate in severity UGN-101 will soon become a standard of treatment for low-grade UTUCs at risk of relapse after either surgery, or nephron-sparing techniques.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Additional information

Funding

This manuscript has not been funded.