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FDA authorizes trial of novel immunotherapy zalifrelimab in NMIBC


The FDA has authorized the launch of a phase 1/2 study exploring zalifrelimab (UGN-301) for the treatment of patients with recurrent non–muscle-invasive bladder cancer (NMIBC), according to Urogen, the developer of the anti–CTLA-4 immunotherapy.1

The multi-arm phase 1 part of the study will assess the safety and tolerability of zalifrelimab and determine the recommended phase 2 dose of the immunotherapy. Phase 2 will evaluate zalifrelimab as a single agent and in combination with other agents. The initial combination explored will be zalifrelimab plus UGN-201, Urogen’s investigational TLR7 agonist.

“We are pleased that our IND application was cleared to proceed, and we can begin to explore our innovative approach to meeting the high unmet needs in bladder cancer, especially for patients with high-grade disease,” Mark Schoenberg, chief medical officer, UroGen, stated in a news release. “Intravesical delivery of combination therapies is unique with the goal of improving efficacy while avoiding the toxicities associated with systemic treatment of immunotherapies. Our proprietary technology enables local delivery of treatments, which provide opportunities to pursue several promising drug combinations.”

UGN-201 is also currently being assessed in a window of opportunity phase 1 study (NCT05055050)2 enrolling patients with bladder cancer undergoing radical cystectomy. The target enrollment of the small open-label trial is 10 patients and the estimated primary completion date is August 31, 2022.

In addition to zalifrelimab and UGN-201, other investigational agents being developed by UroGen include the mitomycin-containing reverse thermal gel UGN-102. In the phase 3 ENVISION study, UGN-102 is being explored as primary chemoablative therapy in patients with low-grade, intermediate-risk NMIBC.3 In the international, single-arm trial, enrolled patients will be administered 6 once-weekly intravesical instillations of UGN-102.

The enrollment goal of ENVISION 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.

The safety and efficacy of UGN-102 in this setting were previously shown in the phase 2b OPTIMA II trial,4 in which 63 patients 63 patients received at least 1 UGN-102 instillation and 57 (90%) patients received 6 UGN-102 instillations. 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.

UroGen’s flagship treatment, UGN-101 (mitomycin gel), known by the trade name Jelmyto, was approved by the FDA in April 2020 for the treatment of patients with low-grade upper tract urothelial cancer.5


1. UroGen Announces FDA Clearance of IND Application for the Investigational Immunotherapy UGN-301 (zalifrelimab) Intravesical Solution in Recurrent Non-Muscle Invasive Bladder Cancer. Published online March 29, 2022. Accessed April 5, 2022. https://bit.ly/3v0xWRP

2. ClinicalTrials.gov. A Window of Opportunity Phase I Study of UGN-201 in Patients With Bladder Cancer Undergoing Radical Cystectomy Protocol #: 2021-0630. Last updated February 21, 2022. Accessed April 1, 2022. https://clinicaltrials.gov/ct2/show/NCT05055050

3. 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

4. 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

5. FDA Approves First Therapy for Treatment of Low-Grade Upper Tract Urothelial Cancer. Published online April 15, 2020. Accessed April 5, 2022. https://bit.ly/3x6Gvgr

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