FDA Approves Mitomycin Gel for Urothelial Cancer

The FDA has approved mitomycin gel (Jelmyto) as the first therapy to treat low-grade upper tract urothelial cancer.

The FDA has approved mitomycin gel (UGN-101; Jelmyto) as the first therapy to treat low-grade upper tract urothelial cancer (UTUC).1

The approval is based on results from the pivotal phase III OLYMPUS trial, in which a final analysis showed that mitomycin gel elicited a complete response (CR) rate of 58% in this patient population. Among the 41 patients who achieved a CR, 19 (46%) continued to respond at 12 months.

“This is the first approval specifically for patients with low-grade UTUC and provides an option for some patients who may otherwise require a nephroureterectomy,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a press release.

“Due to substantial treatment challenges associated with the complex anatomy of the upper urinary tract, many patients need to be treated with radical surgery—usually complete removal of the affected kidney, ureter and bladder cuff. Jelmyto gives patients, for the first time, an alternative treatment option for low-grade UTUC,” added Pazdur.

Mitomycin gel 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 was designed to evaluate the efficacy, safety, and tolerability of mitomycin gel 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 rate.

Moreover, patients in CR will receive mitomycin gel 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. Previously announced results also showed that 45% of tumors were found to be unresectable by surgery at baseline.2

The results of the final analysis also showed that, by Kaplan Meier analysis, the durability of response was approximately 89% at 6 months and 84% at 12 months; the median time to recurrence was estimated to be 13 months.

Regarding safety, the most commonly reported 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%). A total 8.5% of patients reported severe events of ureteric stenosis.

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.3 At the time 6 patients underwent 3-month follow-up and remained in CR.

Previously, the FDA granted mitomycin gel orphan drug designation, fast track designation, and, in October 2018, a breakthrough therapy designation for mitomycin gel in this setting.

“Although our nation’s emphasis is on the need to combat COVID-19, patients with cancer and their unique needs continue to be a top priority for the FDA,” Pazdur stated. “We continue to expedite oncology product development in this critical time. Our staff is continuing to meet virtually with drug developers, academic investigators and patient advocates to push forward the coordinated review of drugs, biologics and devices for cancer.”


  1. FDA Approves First Therapy for Treatment of Low-Grade Upper Tract Urothelial Cancer. Published April 15, 2020. https://bit.ly/2wGE4Es. Accessed April 15, 2020.
  2. UroGen Pharma Announces Positive Results of UGN-101 from Pivotal Phase 3 OLYMPUS Trial for the Non-Surgical Treatment of Patients with Low-Grade Upper Tract Urothelial Cancer (LG UTUC). UroGen Pharma Ltd. Published January 8, 2019. https://bit.ly/2LX0ogq?rel=0". Accessed January 8, 2019.
  3. Kleinmann N, Pierorazio P, Matin S, et al. Non-surgical management of low grade upper tract urothelial cancer: an interim analysis of the international multicenter OLYMPUS trial (NCT02793128). J Urol. 2018;199(4S):e1166. doi: 10.1016/j.juro.2018.03.097.