Phase 3 trial launches of UGN-103 in low-grade, intermediate-risk NMIBC

The first patient has been dosed in the phase 3 UTOPIA trial (NCT06331299) exploring UGN-103, an investigational mitomycin-based formulation under development for the treatment of patients with low-grade, intermediate-risk non–muscle-invasive bladder cancer (LG-IR-NMIBC), according to a news release from UroGen Pharma, the developer of the therapy.¹

Primary completion of the UTOPIA trial is anticipated for March 2025.

According to the company, “Anticipated advantages of UGN-103 include a new formulation of mitomycin that may considerably shorten the manufacturing process and simplify the reconstitution procedure.”

“Reaching this phase 3 trial milestone for UGN-103 highlights our drive to innovate and bring forward cutting-edge treatments for low-grade intermediate-risk non–muscle-invasive bladder cancer,” said Liz Barrett, president and CEO of UroGen, in the news release.¹ “UGN-103 represents a significant step forward, offering potential improvements in manufacturing, convenience, and cost. We are excited about the potential of this next-generation formulation and look forward to furthering its development to advance the care of patients.”

In total, the single-arm, multicenter UTOPIA trial plans to enroll 87 patients with LG-IR-NMIBC across clinical trial sites in the United States.² Patients are eligible for enrollment if they have history of at least 1 prior episode of NMIBC, negative voiding cytology for high-grade disease, adequate organ and bone marrow function, and an anticipated life expectancy of at least the duration of the trial.

For the study, patients will receive 75 mg of UGN-103 via intravesical instillation once weekly for 6 weeks. Complete response, defined as having no detectable disease in the bladder, will be assessed at the 3-month follow-up visit. Those who achieve a complete response at this time point will enter into the follow-up period for the study. During the follow-up period, patients will be assessed every 3 months until disease recurrence, disease progression, death, or until the last patient completes 12 months of follow-up. Those who do not achieve a complete response at the 3-month follow-up visit will receive investigator-determined standard of care option.

The primary end point for the trial is the complete response rate at 3-month follow-up. Second end points include duration of response, durable complete response rate, and safety, all of which may be assessed for up to 21 months.

Primary completion of the study is anticipated for March 2025.

Additional info on UGN-103, UGN-102

UGN-103 for intravesical instillation is expected to follow the potential FDA approval and launch of UGN-102, for which UroGen is currently seeking an indication in LG-IR-NMIBC.

UroGen submitted a new drug application (NDA) for UGN-102 in August 2024. If the NDA is accepted and granted priority review, the application will undergo evaluation by the FDA with the potential for approval as early as the first quarter of 2025.

The NDA for UGN-102 is primarily supported by findings from the phase 3 ENVISION trial (NCT05243550), which met its primary end point by demonstrating a 79.6% complete response rate in patients with LG-IR-NMIBC at 3 months following the first instillation of the therapy.

Updated data from the trial, which was reported in June 2024, showed that the 12-month duration of response (DOR) was 82.3% (95% CI, 75.9%, 87.1%) per Kaplan-Meier estimate among those patients who achieved a complete response at 3 months following the first instillation (n = 108) of UGN-102.³ The study also reported an estimated DOR of 80.9% (95% CI, 73.9%–86.2%) at both 15 (n = 43) and 18 (n = 9) months, per Kaplan-Meier estimates.

Overall, the single-arm, multinational, multicenter, ENVISION trial is evaluating the safety and efficacy of UGN-102 as a primary chemoablative therapy in patients with LG-IR-NMIBC. In total, the study has enrolled approximately 240 adult patients across 56 sites in the United States and Europe.

The ENVISION trial remains ongoing, with final study completion anticipated for 2028.

Reference

1. First patient dosed in phase 3 clinical trial of UGN-103, a next generation mitomycin-based formulation in development for the treatment of low-grade intermediate-risk non-muscle invasive bladder cancer. News release. UroGen Pharma Ltd. October 2, 2024. Accessed October 3, 2024. https://www.businesswire.com/news/home/20241002363009/en/First-Patient-Dosed-in-Phase-3-Clinical-Trial-of-UGN-103-a-Next-Generation-Mitomycin-Based-Formulation-in-Development-for-the-Treatment-of-Low-Grade-Intermediate-Risk-Non-Muscle-Invasive-Bladder-Cancer

2. A phase 3 study of UGN-103 for treatment of patients with low-grade intermediate-risk non-muscle invasive bladder cancer (UTOPIA). ClinicalTrials.gov. Last updated September 19, 2024. Accessed October 2, 2024. https://clinicaltrials.gov/study/NCT06331299

3. UroGen announces unprecedented 82.3% duration of response at 12 months in the ENVISION trial investigating UGN-102 as potentially the first FDA-approved non-surgical treatment for LG-IR-NMIBC. News release. June 13, 2024. Accessed October 3, 2024. https://investors.urogen.com/news-releases/news-release-details/urogen-announces-unprecedented-823-duration-response-12-months