UGN-102 Shows Lasting Responses in Low-Grade, Intermediate-Risk NMIBC
UGN-102 led to durable responses in low-grade, intermediate-risk bladder cancer, per phase 3 study findings at the 2025 Genitourinary Cancers Symposium.
Bladder cancer stages: © pikovit - stock.adobe.com
Findings from the phase 3 ENVISION (NCT05243550) and ATLAS (NCT04688931) studies, presented at the 2025 Genitourinary Cancers Symposium, showed that UGN-102 produced strong and lasting responses in patients with low-grade, intermediate-risk non–muscle-invasive bladder cancer (NMIBC).
In the single-arm ENVISION trial, 79.6% (95% CI, 73.9%-84.5%) of patients with recurrent disease who received UGN-102 (n = 240) achieved a complete response (CR) at 3 months, and the estimated 12-month CR rate was 82.3% (95% CI, 75.9%-87.1%).
In the randomized ATLAS trial, 64.8% (95% CI, 56.3%-72.6%) of patients with newly diagnosed or recurrent disease who received UGN-102 with or without subsequent transurethral resection of bladder tumor (TURBT; n = 142) achieved a CR at 3 months vs 63.6% (95% CI, 55.0%-71.5%) of those who underwent TURBT (n = 140). The Kaplan-Meier estimated 12-month CR rates in these respective arms were 79.7% (95% CI, 69.3%-86.9%) and 67.7% (95% CI, 55.8%-77.1%).
“These results demonstrate that treatment with UGN-102 results in a high and clinically meaningful durable CR rate in patients with newly diagnosed or recurrent low-grade, intermediate-risk NMIBC,” lead study author Sandip M. Prasad, MD, of Morristown Medical Center, Atlantic Medical Group in New Jersey, and coauthors wrote in a poster presentation of the data.
ENVISION and ATLAS Background and Design
TURBT is the current standard of care (SOC) for patients with low-grade, intermediate-risk NMIBC; however, the study authors noted that this treatment method provides inadequate disease control and that patients often need to undergo multiple TURBTs under general anesthesia, which has associated complications, particularly for elderly patients. To address this need, the ENVISION and ATLAS trials studied the efficacy of intravesical treatment with UGN-102, a mitomycin-containing reverse thermal hydrogel, in patients with low-grade, intermediate-risk NMIBC.
Both ENVISION and ATLAS enrolled patients at least 18 years of age with low-grade NMIBC who were diagnosed using cold cup biopsy with visible tumor left in situ; patients needed to have negative voiding cytology for high-grade disease. Intermediate-risk disease was defined per the International Bladder Cancer Group as meeting 1 or 2 of the following criteria: the presence of multiple tumors, a solitary tumor greater than 3 cm, and/or recurrence of low-grade NMIBC within 1 year of the current diagnosis.
In both studies, patients in the UGN-102 arms received UGN-102 via a urinary catheter at 75 mg once weekly for 6 months. In ENVISION, patients with recurrent disease received UGN-102, and those without a CR at 3 months subsequently received SOC treatment and entered the follow-up period. In ATLAS, patients with newly diagnosed or recurrent disease were randomly assigned to receive UGN-102 or TURBT. Those without a CR with residual low-grade disease subsequently received TURBT and entered the follow-up period. All patients in both trials were examined for bladder cancer recurrence using cystoscopy, urine cytology, and for-cause biopsy at 3 months and at regular intervals thereafter.
In ENVISION, the primary end point was CR at 3 months. In ATLAS, the primary end point was disease-free survival (DFS). Secondary end points in both trials included duration of response (DOR) and safety.
Notably, previously reported findings from ATLAS showed that UGN-102 with or without TURBT generated similar estimated DFS outcomes for patients with newly diagnosed vs recurrent disease. The estimated 15-month DFS rate with UGN-102 was 77.4% in patients with newly diagnosed disease vs 63.2% in those with recurrent disease.2
Additional Updated Efficacy Findings
Among the patients in the ENVISION and ATLAS trials, respectively, 68% and 60% were at least 65 years of age; 98% and 99% were White; and 61% and 70% were male.1
The median DOR was not estimable in any of the 3 trial arms because of low recurrence rates. In ENVISION, at a median follow-up for DOR of 13.86 months (95% CI, 12.19-14.52), 17.3% of complete responders (n = 191) had disease recurrence, including low-grade disease (14.1%) and high-grade disease (2.1%). Two patients had died.
The HR for DOR between the 2 arms in ATLAS favored the UGN-102 arm (0.46; 95% CI, 0.24-0.86). In the UGN-102 arm, at a median follow-up for DOR of 12.45 months (95% CI, 12.02-14.13), 19.6% of complete responders (n = 92) had disease recurrence, including low-grade disease (16.3%) and high-grade disease (3.3%). No patients in this arm had died. In the TURBT arm, at a median follow-up for DOR of 12.16 months (95% CI, 11.89-12.75), 27.0% of complete responders (n = 89) had disease recurrence, including low-grade disease (19.1%) and high-grade disease (6.7%). One patient in this arm had died.
Safety Data
The most common adverse effect (AE) observed with UGN-102 across both trials was dysuria, which was reported in 22.5% and 30.4% of patients who received the UGN-102 in ENVISION and ATLAS, respectively.
Previously reported safety findings from ENVISION showed that additional treatment-emergent AEs (TEAEs) with UGN-102 included hematuria (8.3%), urinary tract infection (7.1%), pollakiuria (6.7%), fatigue (5.4%), urinary retention (5.0%), urethral stenosis (4.6%), COVID-19 (3.8%), constipation (3.8%), nausea (3.8%), and micturition urgency (3.3%).3
Previously reported safety findings from ATLAS demonstrated that additional TEAEs in the UGN-102 and TURBT arms, respectively, included micturition urgency (18%; 7.6%), nocturia (18%; 6.8%), pollakiuria (16%; 6.1%), flatulence (9.4%; 3.0%), COVID-19 (8.0%; 6.1%), erectile dysfunction (6.5%; 3.0%), hematuria (6.5%; 4.5%), and malaise (5.8%; 1.5%).4
“UGN-102 may represent an efficacious and well-tolerated treatment option for patients with low-grade, intermediate-risk NMIBC,” the authors concluded in the poster.1
References
Prasad S, Hu B, Bjurlin M, et al. Treatment of low-grade intermediate-risk non-muscle-invasive bladder cancer with UGN-102: results of the phase 3 ATLAS and ENVISION studies. J Clin Oncol. 2025;43(suppl 5):777. doi:10.1200/JCO.2025.43.5_suppl.777
Prasad SM, Huang WC, Shore ND, et al. Response to primary chemoablation with UGN-102 in patients with new or recurrent LG IR NMIBC: post-hoc analysis of the ATLAS trial. J Urol. Published online May 1, 2024. doi:10.1097/01.JU.0001008848.77629.6f.09
Prasad SM, Shishkov D, Mihaylov NV, et al. Primary chemoablation of recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer with UGN-102: a single-arm, open-label, phase 3 trial (ENVISION). J Urol. 2025;213(2):205-216. doi:10.1097/JU.0000000000004296
Prasad SM, Huang WC, Shore ND, et al. Treatment of low-grade intermediate-risk nonmuscle-invasive bladder cancer with UGN-102 ± transurethral resection of bladder tumor compared to transurethral resection of bladder tumor monotherapy: a randomized, controlled, phase 3 trial (ATLAS). J Urol. 2023;210(4):619-629. doi:10.1097/JU.0000000000003645
