Primary Chemoablation of Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer Using UGN-102, a Mitomycin-Containing Reverse Thermal Gel (Optima II): A Phase 2b, Open-Label, Single-Arm Trial

K Kent Chevli, Neal D Shore, Andrew Trainer, Angela B Smith, Daniel Saltzstein, Yaron Ehrlich, Jay D Raman, Boris Friedman, Richard D'Anna, David Morris, Brian Hu, Mark Tyson, Alexander Sankin, Max Kates, Jennifer Linehan, Douglas Scherr, Steven Kester, Michael Verni, Karim Chamie, Lawrence Karsh, Arnold Cinman, Andrew Meads, Soumi Lahiri, Madlen Malinowski, Nimrod Gabai, Sunil Raju, Mark Schoenberg, Elyse Seltzer, William C Huang, K Kent Chevli, Neal D Shore, Andrew Trainer, Angela B Smith, Daniel Saltzstein, Yaron Ehrlich, Jay D Raman, Boris Friedman, Richard D'Anna, David Morris, Brian Hu, Mark Tyson, Alexander Sankin, Max Kates, Jennifer Linehan, Douglas Scherr, Steven Kester, Michael Verni, Karim Chamie, Lawrence Karsh, Arnold Cinman, Andrew Meads, Soumi Lahiri, Madlen Malinowski, Nimrod Gabai, Sunil Raju, Mark Schoenberg, Elyse Seltzer, William C Huang

Abstract

Purpose: Low-grade intermediate-risk nonmuscle-invasive bladder cancer (LG IR NMIBC) is a recurrent disease, thus requiring repeated transurethral resection of bladder tumor under general anesthesia. We evaluated the efficacy and safety of UGN-102, a mitomycin-containing reverse thermal gel, as a primary chemoablative therapeutic alternative to transurethral resection of bladder tumor for patients with LG IR NMIBC.

Materials and methods: This prospective, phase 2b, open-label, single-arm trial recruited patients with biopsy-proven LG IR NMIBC to receive 6 once-weekly instillations of UGN-102. The primary end point was complete response (CR) rate, defined as the proportion of patients with negative endoscopic examination, negative cytology and negative for-cause biopsy 3 months after treatment initiation. Patients with CR were followed quarterly up to 12 months to assess durability of treatment effect. Safety and adverse events were monitored throughout the trial.

Results: A total of 63 patients (38 males and 25 females 33-96 years old) enrolled and received ≥1 instillation of UGN-102. Among the patients 41 (65%) achieved CR at 3 months, of whom 39 (95%), 30 (73%) and 25 (61%) remained disease-free at 6, 9 and 12 months after treatment initiation, respectively. A total of 13 patients had documented recurrences. The probability of durable response 9 months after CR (12 months after treatment initiation) was estimated to be 73% by Kaplan-Meier analysis. Common adverse events (incidence ≥10%) included dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection and fatigue.

Conclusions: Nonsurgical primary chemoablation of LG IR NMIBC using UGN-102 resulted in significant treatment response with sustained durability. UGN-102 may provide an alternative to repetitive surgery for patients with LG IR NMIBC.

Trial registration: ClinicalTrials.gov NCT03558503.

Keywords: clinical trial; mitomycin; phase II; urinary bladder neoplasms.

Conflict of interest statement

JL, DM, JDR and DSa report acting as investigators and consultants/advisors for UroGen Pharma; KC, BH, NDS and ABS report serving as consultants/advisors for UroGen Pharma; NG, SL, MM, AM, SR, MS and ES are full-time employees of UroGen Pharma; MT reports serving as an assistant editor for The Journal of Urology®; KKC, AC, RD’A, YE, BF, WCH, LK, MK, SK, AS, DSc, AT and MV report no direct or indirect commercial financial incentive associated with publishing the article.

Figures

Figure 1.
Figure 1.
Flow diagram.
Figure 2.
Figure 2.
Kaplan-Meier plot of duration of CR (3-month CR analysis set).

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Source: PubMed

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