UGN-102 Presents as a Surgical Alternative for Low-Grade Intermediate Risk NMIBC

Durable responses were shown with the investigational agent UGN-102 (mitomycin) as treatment of patients with low-grade intermediate-risk non-muscle invasive bladder cancer (NMIBC), according to final results of the phase 2b OPTIMA II study (NCT03558503).¹

Findings, announced in a press release from the developer of the agent, UroGen Pharma Ltd., revealed a 72.5% duration of response (DOR), which was an estimate from a Kaplan-Meir analysis. The median DOR was not reached in the study. These durable responses add to previously reported positive results from this trial, which showed complete responses in 65% of the 63 patients who received UGN-102. The responses were observed 3 months after the start of therapy. Based on these findings, a phase 3 study of UGN-102 versus the standard of care therapy is planned to initiate by the end of 2020.

“The current approach to treating patients diagnosed with low-grade intermediate risk non-muscle invasive bladder cancer is surgery. In most cases, the cancer comes back and repetitive surgical intervention is required. This puts a tremendous burden on patients and their families and can even be life-threatening,” said Andrea Maddox-Smith, chief executive officer, Bladder Cancer Advocacy Network, in a statement. “Being able to provide patients with an alternative, non-surgical treatment option that is effective, well-tolerated and durable, would greatly benefit those in the patient community.”

To guide the non-surgical approach, study enrollment was open to patients if they had intermediate-risk disease defined as having either multiple tumors, a solitary tumor >3 cm, and/or at least 1 occurrence within a year of diagnosis. Patients with negative voiding cytology for high-grade disease were also eligible. Patients were excluded if they had a history of carcinoma in situ in the past 5 years, high-grade papillary urothelial carcinoma (UC) within the past 2 years, or Bacille Calmette-Guérin treatment for UC within the past 2 years. The study also excluded patients with prior or current muscle-invasive or metastatic UC or concurrent upper tract UC were also excluded from participating in the trial.^1-3

Patients were given 6 weekly intravesical instillations of 75 mg UGN-102 in an office setting. The patients were assessed after 3 months and followed for durability at the 6-month, 9-month, and 12-month visits. Patient were also evaluated for safety as a secondary end point.

The final results showed that UGN-102 was well-tolerated in patients with low-grade, intermediate-risk NMIBC. At least 10% of patients in the study experienced adverse events (AEs), of which the most common were mild to moderate in severity. These AEs included dysuria, urinary frequency, hematuria, urinary urgency, urinary tract infection and fatigue. There were no serious AEs reported in this analysis.¹

“We are extremely encouraged by the OPTIMA II data and believe UGN-102 has the potential to provide a safe, durable, outpatient treatment alternative for low-grade intermediate risk non-muscle invasive bladder cancer,” stated Mark Schoenberg, MD, chief medical officer at UroGen. “We look forward to the expected initiation of our phase 3 trial this year and further exploring the potential of our innovative technology in advancing new treatments for specialty cancers and urologic diseases.”

_References:

_{1. Complete and durable responses observed in OPTIMA II phase 2b final results for ugn-102 in patients with low-grade intermediate risk non-muscle invasive bladder cancer. News release. UroGen Pharma Ltd. November 17, 2020. Accessed November 17, 2020. https://bit.ly/3nw0tcs}

_{2. Huang W, Chevli K, Trainer A, et al. Can TURBT be avoided? Primary chemoablation with a reverse thermal gel containing mitomycin (UGN-102) in patients with low grade intermediate risk non-muscle invasive bladder cancer. J Urol. 2020;203(suppl 4):LBA02-03. doi:10.1097/JU.0000000000000958.03}

_{3. UroGen Pharma announces first presentation of data from phase 2b study of UGN-102 in patients with difficult to treat type of bladder cancer [news release]. Princeton, NJ: UroGen Pharma Ltd.; May 15, 2020. https://bwnews.pr/2Z87qYm. Accessed May 15, 2020.}