The first patient has been treated in a phase 3b study exploring home instillation of UGN-102 for patients with low-grade, intermediate-risk non–muscle-invasive bladder cancer (NMIBC), according to UroGen Pharma, the company developing the mitomycin-containing reverse thermal gel.1
The goal of the trial is to determine if patients with NMIBC can be treated with UGN-102 at home by a healthcare professional to avoid needing to travel multiple times to a clinical setting to receive the treatment instillations.
“The ease of UGN-102 instillation is of great benefit to these patients who are generally older, suffer from multiple comorbidities, and often rely on caregivers to drive them to medical appointments,” Mark Schoenberg, MD, chief medical officer of UroGen, stated in a press release. “Home instillation is especially convenient for the patient and less burdensome for caregivers as they navigate persistent challenges caused by repeated medical appointments. We look forward to demonstrating the versatility of UGN-102 in this study as we prepare to initiate the single-arm, pivotal phase 3 ENVISION Study of UGN-102 in early 2022.”
Overall, the trial has a target enrollment goal of 10 patients across 4 clinical locations. Patients will be treated with 6 once-weekly intravesical instillations of UGN-102. Dose 1 will be administered by a physician at 1 of the 4 clinical sites. The remaining 5 doses will be administered at the patient’s home. These home instillations will be given by trained home health professionals.
The end points of the study include treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of special interest, discontinuations, and laboratory abnormalities.
Efficacy of UGN-102 was shown in the phase 2b OPTIMA II trial (NCT03558503) published in the Journal of Urology, which demonstrated that nonsurgical primary chemoablation with UGN-102 may be an alternative to repetitive surgery for patients with low-grade NMIBC.2
The study specifically focused on patients with intermediate-risk NMIBC. At 3-months after treatment initiation, the complete response (CR) rate with UGN-102 in these patients was 65%. Using Kaplan-Meier analysis, the researchers estimated that the probability of maintaining a durable response 9 months after achieving a CR (12 months after starting treatment) was 73%.
In the multicenter prospective, open-label, single-arm OPTIMA II 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.
Overall, 41 of the 63 patients achieved a CR 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 CR), 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.
1.First Patient Dosed in UroGen Pharma’s Home Instillation Study of UGN-102 in Patients with Low-Grade Intermediate Risk Non-Muscle Invasive Bladder Cancer (LG IR-NMIBC). Published online December 21, 2021. Accessed December 22, 2021. https://bit.ly/3pjPUwQ.
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