UroGen has announced topline findings from the ongoing phase III OLYMPUS trial, in which the investigational mitomycin formulation UGN-101 (mitomycin gel) demonstrated a 57% complete response rate in patients with low-grade upper-tract urothelial cancer.
Mark P. Schoenberg, MD
Consistent with interim findings presented in May 2018, UroGen has announced topline findings from the ongoing phase III OLYMPUS trial, in which the investigational mitomycin formulation UGN-101 (mitomycin gel) demonstrated a 57% complete response (CR) rate in patients with low-grade upper-tract urothelial cancer (UTUC).1
Investigators observed the CR rate at patients’ primary disease evaluation, which was conducted 4 to 6 weeks after completion of treatment with UGN-101. Evaluated patients who achieved CR remained disease free at 6 months.
UGN-101 received a breakthorough therapy designation from the FDA in October 2018 for instillation as a treatment for patients with low-grade UTUC, which included data from the OLYMPUS trial. In December 2018, UroGen initiated a rolling submission of a new drug application with the FDA for UGN-101 in this setting.
“We are pleased to report that the CR and durability data remain consistent with the interim analysis presented in May 2018. These results continue to validate the potential of UGN-101 to shift the surgical treatment paradigm and benefit patients whose only alternative would be repetitive endoscopic surgical intervention or complete loss of a kidney,” said Mark P. Schoenberg, MD, chief medical officer of UroGen, the manufacturer of UGN-101. “The durability observed in the OLYMPUS study provides further evidence that the non-surgical treatment of LG UTUC with UGN-101 may result in clinically meaningful, recurrence free survival.”
UGN-101 uses the RTGel™ technology platform and is designed to permit longer exposure of mitomycin to urinary tract tissue, which allows for the nonsurgical treatment of these tumors. The therapy is administered to patients using standard ureteral catheters.
The prospective, international, multicenter, open-label, single-arm OLYMPUS trial (NCT02793128) was designed to evaluate the efficacy, safety, and tolerability of UGN-101 in patients with low-grade UTUC. 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.
Those who previously received Bacillus Calmette-Guérin within the past 6 months, had untreated concurrent urothelial cancer in other sites aside from the target area, prior carcinoma in situ in the urinary tract, prior 5-year history of invasive urothelial carcinoma in the urinary tract, prior 2-year history of high-grade papillary urothelial carcinoma in the urinary tract, or is actively being treated or intends to be treated with chemotherapy are excluded.
Investigators enrolled 71 patients with low-grade UTUC who received 4 mg mitomycin C (MMC) concentration per 1 mL of TC-3 gel, with a maximum dose of 15 ml for 6 once-weekly intravesical instillations. The co-primary endpoints were CR, which was defined as a negative ureteroscopic evaluation and negative wash cytology and adverse events (AEs) rate.
Moreover, patients in CR will receive UGN-101 once monthly as maintenance treatment for 11 instillations or the first recurrence, whichever comes first.
Secondary endpoints included long-term durability of CR, CR rate at 3, 6, and 9 months after evaluation, partial response, MMC level in the plasma for select patients.
Sixty-one patients were evaluated for CR; primary disease evaluation is awaited in the remaining 10 patients. Results also showed that 45% of tumors were found to be unresectable by surgery at baseline. Of those who achieved CR, the company noted that half of the patients have 6-month durability.
Regarding safety, UGN-101 was found to be associated with mild or moderate treatment-emergent AEsincluding ureteral narrowing and hydronephrosis, urinary tract infection, flank plain, and creatine elevation—which were transient and coincided with ureteral procedures.
In an interim analysis of the OLYMPUS study of 28 evaluable patients, the CR rate in the intent-to-treat (ITT) cohort was 57%, with 5 patients who had not undergone their assessment.2At the time 6 patients underwent 3-month follow-up and remained in CR.