UroGen Pharma Ltd
This was a Phase III multicenter, single-arm study evaluating the efficacy, safety, and tolerability of UGN-101 in the treatment of low-grade, non-invasive upper tract urothelial cancer. Patients had to have at least one lesion measuring between 5 and 15 mm left in place prior to treatment on this trial. Patients were treated by six weekly instillations of UGN-101 via a retrograde injection through a ureteral catheter and then evaluated 4-6 weeks after the last instillation.
Upper tract urothelial cancer is difficult to treat given its relative scarcity compared to bladder urothelial cancer and the difficulties in delivering effective instillation of treatment within the upper urinary tract. UGN-101 is a novel investigational formulation of mitomycin C (MMC) admixed with a reverse thermal hydrogel that can be instilled as a liquid but that solidifies into a gel at body temperature. This allows for longer exposure of the urinary tract to MMC. Therefore, UGN-101 is an attractive agent for upper tract urothelial cancer that is unresectable and at high risk of recurrence.
The primary endpoint was a complete response (CR) rate defined as the percent of patients who achieved CR at the primary disease evaluation (PDE) visit which occurred on average at 11 weeks following initiation of treatment. The PDE consisted of ureteroscopy with biopsy of any remaining tumor and urine cytology. Patients who achieved CR at PDE were then treated once monthly with a maintenance regimen of UGN-101 for up to an additional 11 months or first recurrence.
This trial is trailblazing as it represents the first phase III trial in upper tract urothelial cancer. Furthermore, it demonstrates the tumor-ablative capacity of UGN-101 especially in patients deemed to be unresectable endoscopically at the start of the trial. Although serious side effects were seen, the mean age of patients was approximately 71 years and the fatal events were not deemed to be related to UGN-101. Furthermore, the side effects of ureteral narrowing and stricture could also have been due to the natural history of the disease and so without a comparator control group, it is hard to know if an observation cohort would have had the same side effects or not.
The trial successfully enrolled 71 patients. Forty-two (59%) of the patients achieved a CR at the PDE visit. Of the 71 patients, 34 (48%) were deemed to have unresectable disease by their treating urologist and 19 (56%) of these “unresectable” patients achieved CR at the PDE visit. At 6 months of follow-up, 85% of evaluable patients with unresectable disease and 89% overall remained disease-free. The most common treated-related adverse events (AEs) were urinary tract infections, ureteral narrowing, and ureteral stricture formation. However, most of these were characterized as mild and resolved on follow-up.