Phase 3 study launches of UGN-102 in low-grade NMIBC

The phase 3 ENVISION study has launched exploring the mitomycin-containing reverse thermal gel UGN-102 as primary chemoablative therapy in patients with low-grade, intermediate-risk non-muscle invasive bladder cancer (NMIBC).¹

In the international, single-arm ENVISION trial, enrolled patients will be administered 6 once-weekly intravesical instillations of UGN-102. The enrollment goal is approximately 220 patients who will be treated across 90 sites. The primary end point is the rate of complete response 3 months after the initial instillation. The key secondary end point will be the durability of these complete responses.

Sandip Prasad, MD

“The start of the ENVISION trial marks the final phase of validating primary chemoablation for the treatment of recurrent intermediate risk NMIBC,” Sandip Prasad, MD, a urologist at Atlantic Health System, Morristown Medical Center, New Jersey, and lead study investigator for the ENVISION trial, stated in a news release. “This study is designed to support the clinical potential of UGN-102 as a new treatment for patients that are under-served by the current standard of care, including those patients at risk for recurrence and those that are unwilling or unable to endure surgery or anesthesia.”

Phase 2b OPTIMA II trial

UroGen, the developer of UGN-102, explained in the news release that the ENVISION study design is similar to the design of the phase 2b OPTIMA II trial “in that patients will have the same clinical characteristics, treatment regimen, assessment, and qualitative follow up but with different endpoints.”

Data from the OPTIMA II trial were previously published in the Journal of Urology.² In the multicenter prospective, open-label, single-arm trial, 63 patients with biopsy-proven, low-grade, intermediate-risk NMIBC were treated with up to 6 once-weekly UGN-102 instillations. The median age was 63 years (range, 33-96) and there were 38 males and 25 females. Twenty-seven patients were aged <65 years, 11 were aged 65 to <75 years, and 25 were aged ≥75 years. Most (n = 55) patients were Caucasian.

Overall, 72.1% of patients had tumors ≤3 cm, 98.4% had noninvasive papillary sarcoma, and 98.4% had low-grade papillary urothelial carcinoma. Prior low-grade NMIBC episodes occurred in 77.8% of patients and 44.4% had a low-grade NMIBC episode ≤1 year of their current diagnosis. The median number of prior TURBTs in recurrent patients was 3 (range, 0-13), including 37 and 28 patients who had received ≥2 and ≥3 prior TURBTs, respectively.

All 63 patients received at least 1 UGN-102 instillation and 57 (90%) patients received all 6 UGN-102 instillations. The primary end point of the study was complete response.

Overall, 41 (65%) of the 63 patients achieved a complete response at the 3-month follow-up from the start of treatment. In this group, 39 (95%) patients remained disease-free at 6 months following the start of treatment (3 months after achieving a complete response), 30 (73%) were disease-free 9 months after starting treatment, and 25 (61%) were disease-free 12 months after starting treatment.

The majority of adverse events (AEs) were considered to be mild to moderate. Overall, 63% (n = 40) of patients had treatment-emergent AEs (TEAEs) that investigators categorized as related to UGN-102 itself or procedure. All-grade TEAEs occurring in ≥10% of patients included dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection, and fatigue. There were no serious TEAEs related to the study treatment or procedure.

Beyond the ENVISION trial, UGN-102 is also being explored in the ongoing global, randomized, open-label, phase 3 ATLAS trial (NCT04688931), which is comparing UGN-102 with or without TURBT versus TURBT alone in patients with low-grade, intermediate-risk NMIBC.

“We have achieved consistent results with similar study designs in the past and believe that it increases our probability for technical and regulatory success for UGN-102 in patients with low-grade, intermediate-risk NMIBC,” Mark Schoenberg, MD, Chief Medical Officer, UroGen, stated in the news release. “We look forward to reporting data from ATLAS and acquiring new scientific evidence from ENVISION as we continue to explore the potential benefits of chemoablation in other types of bladder cancer, including high-grade disease and other specialty cancers.”

References

1. UroGen Announces Start of Pivotal Single-Arm Phase 3 Trial for UGN-102, an Investigational Non-Surgical Treatment for Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer. Published online February 3, 2022. Accessed February 2022. https://bit.ly/35S209n

2. Chevli KK, Shore ND, Trainer A, Smith AB, et al. Primary chemoablation of low-grade intermediate-risk non-muscle-invasive bladder cancer using ugn-102, a mitomycin-containing reverse thermal gel (OPTIMA II): A phase 2b, open-label, single-arm trial. [published online ahead of print August 26, 2021. J Urol. doi: 10.1097/JU.0000000000002186