UGN-102 May Serve as Surgical Alternative for Low-Grade NMIBC With Intermediate Risk

May 15, 2020

"These interim data demonstrate that primary chemoablation of low-grade intermediate-risk non–muscle invasive bladder cancer using UGN-102 results in a significant treatment response and encouraging durability."

Primary chemoablation with UGN-102 (mitomycin) demonstrated significant activity in patients with low-grade, intermediate-risk non–muscle invasive bladder cancer (NMIBC), according to interim results from the phase IIb OPTIMA II trial.1,2

Complete responses (CRs) were achieved by 65% of patients only 3 months after initiating treatment with UGN-102.

As such, the investigators have suggested that UGN-102 could be used as a non-surgical treatment option for patients with low-grade, intermediate-risk NMIBC.

“These interim data demonstrate that primary chemoablation of low-grade intermediate-risk non–muscle invasive bladder cancer using UGN-102 results in a significant treatment response and encouraging durability,” said investigator William C. Huang, MD, a urologic oncologist at the NYU Langone Medical Center. His presentation of the OPTIMA II trial was made available as part of the American Urological Association (AUA) Virtual Experience platform for the 2020 AUA Annual Meeting.1

“The interim results from OPTIMA II indicate that UGN-102, if approved, may provide an effective, non-surgical treatment option for these patients that is both well-tolerated and durable,” Huang commented further in a press release.2

Transurethral resection of the bladder (TURBT) and intravesical therapy are considered the standard of care for treating patients with low-grade, intermediate-risk NMIBC, which is defined as multiple and/or recurrent low-grade Ta tumors.

The use of a single intravesical instillation of mitomycin C after TURBT was previously shown to reduce the risk of recurrence in patients with NMIBC.3

UGN-102 is a reverse thermo-gelation hydrogen that contains mitomycin.1 The gel formation is delivered into the body using a standard urinary catheter at a low temperature where it takes liquid form, then it is warmed to body temperature and becomes a gel for exposure to mitomycin for up to 6 hours in the bladder, Huang explained.

OPTIMA II (NCT03558503) was initiated to explore the efficacy and safety of UGN-102 for primary chemoablation in patients with low-grade, intermediate-risk NMIBC as a nonsurgical alternative to TURBT. The trial is an ongoing prospective single-arm, open-label phase II study.

In terms of eligibility for the study, intermediate risk was 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. Exclusion criteria consisted of those with 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. Patients with prior or current muscle-invasive or metastatic UC or concurrent upper tract UC were also excluded from participating in the trial.

A total of 63 patients were enrolled and treated with 6 once-weekly instillations of UGN-102. Patients were evaluated after 3 months for the primary end point of CR rate and followed for durability at the 6-, 9-, and 12-month visits. Safety was an additional secondary end point.

The mean age of all patients was 70.5 years (range, 33-96) and men made up 60% of the population. Ninety-eight percent of patients had noninvasive papillary carcinoma and 82% had multiple tumors.

As of the interim analysis, 36 patients were evaluable for response duration at 6 months with 35 maintaining their response at 6 months (97.2%; 95% CI, 85.5%-99.9%). At 9 months, 24 of 28 evaluable patients had ongoing CR (85.7%; 95% CI, 67.3%-96.0%), and 11 of 13 evaluable patients (84.6%; 95% CI, 54.6%-98.1%) had durable CRs at 1 year.

At least 1 adverse event (AE) was observed in 91% of patients, 64% had a study drug or procedure–related treatment-emergent AE, and 6 patients (10%) discontinued treatment due to a treatment-emergent AE. One patient (1.6%) died due to an AE, and 5 patients (7.9%) had at least 1 serious AE.

The most common AEs observed with UGN-102 treatment were on the lower urinary tract, Huang commented, and consisted of dysuria (41%), pollakiuria (19%), hematuria (14%), fatigue (13%), micturition urgency (13%), and urinary tract infection (11%).

UroGen Pharma announced that it intends to advance the study of UGN-102 for patients with low-grade intermediate-risk NMIBC to a pivotal study.2

References:

1. 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

2. 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.

3. Bosschieter J, Nieuwenhuijzen JA, van Ginkel T, et al. Value of an immediate intravesical instillation of mitomycin C in patients with non-muscle-invasive bladder cancer: a prospective multicentre randomised study in 2243 patients. Eur Urol. 2018;73(2):226-232. doi:10.1016/j.eururo.2017.06.038