Efficacy determination was based on OLYMPUS (NCT02793128), an ongoing, single-arm, multicenter trial enrolling 71 patients with treatment-naïve or recurrent low-grade non-invasive UTUC with at least one measurable papillary tumor located above the ureteropelvic junction. Patients who had larger tumors could have had prior tumor debulking. Patients received weekly JELMYTO 4 mg per mL instillations via ureteral catheter or nephrostomy tube for 6 weeks. For patients with a complete response (CR) at 3 months, instillations were to be administered monthly for a maximum of 11 additional instillations.
The major efficacy outcome measures were CR and CR durability. CR was defined as complete absence of tumor lesions 3 months after JELMYTO initiation and was assessed by urine cytology and ureteroscopy. If warranted, a biopsy was performed. Forty-one patients (58%) achieved a CR three months following treatment initiation and were continued in follow-up; 29 patients received at least one dose of maintenance therapy.
Durability of response in those with CRs was evaluated at 3, 6, 9 and 12 months, following the CR determination. Seven patients had documented recurrences and nineteen patients remained in CR at 12-months following CR determination. The median response duration had not been reached (range: 0, 18.8+ months).
The most common adverse reactions (≥ 20%) in patients who received JELMYTO were ureteric obstruction, flank pain, urinary tract infection, hematuria, renal dysfunction, fatigue, nausea, abdominal pain, dysuria, and vomiting. Ureteric obstruction occurred in 58% of those receiving JELMYTO and required ureteral stent placement in 88% of these patients.
The recommended JELMYTO dose is 4 mg per mL instilled via a ureteral catheter or nephrostomy tube, with total instillation volume based on volumetric measurements using pyelography, not exceeding 15 mL (60 mg mitomycin).
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
FDA granted this application priority review, fast track, and breakthrough therapy designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Source: "FDA Approves Mitomycin For Low-Grade Upper Tract Urothelial Cancer". 2020. U.S. Food And Drug Administration.
Watch: Nephron-Sparing Management of Low-Grade UTUC with UGN-101 (Mitomycin Gel) for Instillation: The Olympus Trial Experience - Seth Lerner