Investigational LG-IR-NMIBC treatment UGN-102 found to have long-term durability

Recently reported data show a median durability of response (DOR) of 24.4 months for UGN-102 (mitomycin) for intravesical solution, an investigational drug in phase 3 development for treatment of low-grade intermediate risk non–muscle-invasive bladder cancer (LG-IR-NMIBC).¹

The data were obtained through an ongoing, noninterventional rollover study from the OPTIMA II trial, and the findings were presented at the 23rd Annual Society of Urologic Oncology meeting in San Diego, California.

William C. Huang, MD, says "The OPTIMA II Phase 2b trial showed significant tumor response benefit for patients using the novel chemoablative therapy UGN-102 for LG-IR-NMIBC and this latest analysis shows that the treatment benefit lasted for more than 2 years."

“LG-IR-NMIBC is a challenging disease to treat because of the high recurrence rate managed by repetitive surgeries. The OPTIMA II Phase 2b trial showed significant tumor response benefit for patients using the novel chemoablative therapy UGN-102 for LG-IR-NMIBC and this latest analysis shows that the treatment benefit lasted for more than 2 years. I look forward to additional data on UGN-102, including evidence from the ENVISION phase 3 study,” principal investigator William C. Huang, MD, FACS, said in a news release on the findings.²

The initial OPTIMA II trial (NCT03558503) was a phase 2b clinical trial that evaluated the safety and efficacy of UGN-102 as a primary chemoablative treatment for patients with LG-IR-NMIBC. From the data collected in the trial, investigators concluded that treatment response from UGN-102 showed sustained durability for patients with LG-IR-NMIBC and may provide an alternative to surgery. Patients were eligible to participate in the rollover study to evaluate the long-term durability of the findings on UGN-102 if they had completed the OPTIMA II trial.

At the time of data cutoff for the rollover study, data were collected on 15 patients who met the eligibility criteria. Outcomes of interest for the investigators included DOR in patients who remained in complete response (CR) at the end of OPTIMA II, events of disease recurrence and progression, post-study treatments, and death.

The median DOR among the 15 patients in the study was 24.4 months (range, 10.1 to 30.7 months). At the time of analysis, 7 patients remained in CR, 6 patients had a recurrence of LG disease, 1 patient had progression to high-grade disease, and 1 patient withdrew consent but remained in CR at the last evaluation prior to discontinuation. Among all participants, 5 had post-study treatment with transurethral resection of the bladder tumors (n = 3) or fulguration (n = 2).

“UGN-102 uses a similar combination with a simpler delivery method to our currently approved chemoablative medicine and has showed a similar durability of response in LG-IR-NMIBC. UroGen’s proprietary RTGel technology allows medicines to dwell for several hours potentially improving the therapeutic effects of existing medicines. If approved, UGN-102 would be the only primary non-surgical treatment option for patients with LG-IR-NMIBC who often recur within one year of receiving surgery and continue to need repetitive surgeries for the rest of their life,” Mark Schoenberg, MD, chief medical officer of UroGen, said in the news release.

Investigators concluded that the interim results from the ongoing rollover study suggest durability of UGN-102 for treatment of patients with LG-IR-NMIBC. The use of the drug as a primary chemoablative treatment is being further assessed in the phase 3 ENVISION trial (NCT05243550), which is currently enrolling participants.

ENVISION seeks to enroll 220 patients with LG-IR-NMIBC with the goal of evaluating the safety and efficacy of UGN-102.The primary end point assessed will be complete response rate at a 3-month follow-up, and secondary end points will include duration of response, durable complete response rate, disease-free survival, and incidence of treatment-emergent adverse events. The estimated primary completion date for the trial is February 2023.

Overall OPTIMA II trial data

Data from the prospective, phase 2b, open-label, single-arm OPTIMA II clinical trial were presented at the 2021 American Urological Association Annual Meeting.³

The study cohort consisted of 38 male patients and 25 female patients aged from 33 to 96 years of age with biopsy-proven LG-IR-NMIBC. Participants in the study received 6 once-weekly instillations of UGN-102.

Results from the 63 patients showed a CR rate of 65% (41 patients) at 3 months, of which 95% (39 patients), 73% (30 patients), and 61% (25 patients) remained disease-free at 6, 9, and 12 months, respectively. A Kaplan-Meier analysis estimated the probability of durable response 9 months after CR (12 months after treatment initiation) to be 73%. Of all participants, 13 patients had instances of disease recurrence.

Incidence of adverse events (AEs) was found to be at least 10%, and common AEs included dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection, and fatigue.

References

1. Chevli KK, Shore ND, Trainer A, et al. Long-term outcomes of treatment with UGN-102 for primary chemoablation of low-grade intermediate risk non-muscle—invasive bladder cancer (LG IR NMIBC). Presented at: Society of Urologic Oncology 23rd Annual Meeting; November 30-December 2, 2022; San Diego, California. Poster 193. https://suo-abstracts.secure-platform.com/a/gallery/rounds/15/details/2419

2. UroGen announce new data from the OPTIMA II study that show median durability of response of 24.4 months for UGN-102, an investigational non-surgical chemoablative treatment for low-grade, intermediate-risk non-muscle invasive bladder cancer. News release. UroGen. December 2, 2022. Accessed on December 6, 2022. https://www.businesswire.com/news/home/20221202005055/en

3. Chevli KK, Shore ND, Trainer A, et al. 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. Presented at: 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual.