Treatment of low-grade intermediate-risk non-muscle-invasive bladder cancer with UGN-102: Results of the phase 3 ATLAS and ENVISION studies.

777 Background: The ATLAS and ENVISION phase 3 studies (NCT04688931/NCT05243550) treated patients with low-grade intermediate-risk non-muscle-invasive bladder cancer (LG-IR-NMIBC) with UGN-102, a reverse thermal hydrogel containing mitomycin. Primary efficacy and safety results were previously reported for the individual studies; here we report additional data. Methods: In the randomized controlled ATLAS study, patients with newly diagnosed or recurrent LG-IR-NMIBC were randomized to 6 weekly intravesical instillations of UGN-102 (n=142) or transurethral resection of bladder tumor (TURBT) (n=140). In the single-arm ENVISION study, patients with recurrent LG-IR-NMIBC received 6 weekly intravesical instillations of UGN-102 (n=240). In both trials, patients were examined for recurrence of bladder cancer using cystoscopy, urine cytology testing, and for-cause biopsy at 3 months, and in those with a complete response (CR), at regular intervals thereafter. Duration of response (DOR) was calculated using the Kaplan–Meier method. Results: In both studies (ATLAS, ENVISION) patients were mostly aged ≥65 years (60%, 68%), white (99%, 98%), and male (70%, 61%). In the ATLAS study, 89 patients (63.6%) in the TURBT arm and 92 patients (64.8%) in the UGN-102 arm had a CR at 3 months. Among patients achieving a CR at 3 months in ATLAS, 79.7% in the UGN-102 arm vs 67.7% in the TURBT arm remained event free 12 months later; the majority with recurrence had low-grade (LG) disease (Table). In ENVISION, 79.6% had a CR at 3 months, and 82.3% remained event free 12 months later, again with the majority of recurrence being LG disease (Table). Median DOR was not estimable in any arm due to low recurrence rates, with a between arms hazard ratio in ATLAS of 0.46 (95% CI 0.24–0.86) favoring the UGN-102 arm. The most common adverse event with UGN-102 in both studies was dysuria, occurring in 30.4% in ATLAS and 22.5% in ENVISION. Conclusions: In both studies, CR rate in patients initially treated with UGN-102 was robust, with the majority of patients remaining event-free at 12 months follow-up. 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 LG-IR-NMIBC. UGN-102 may represent a valuable non-surgical treatment option for these patients. Clinical trial information: NCT04688931 / NCT05243550 . ATLAS ENVISION UGN-102 TURBT UGN-102 CR at 3 months 92/142 (64.8%) 89/140 (63.6%) 191/240 (79.6%) CR rate (95% CI) 64.8 (56.3–72.6) 63.6 (55.0–71.5) 79.6 (73.9–84.5) Follow-up time for DORMedian (95% CI) 12.45 (12.02–14.13) 12.16 (11.89–12.75) 13.86 (12.19–14.52) Any recurrence 18/92 (19.6%) 24/89 (27.0%) 33/191 (17.3%) LG disease 15/92 (16.3%) 17/89 (19.1%) 27/191 (14.1%) HG disease 3/92 (3.3%) 6/89 (6.7%) 4/191 (2.1%) Death 0 1/89 (1.1%) 2/191 (1.0%) HG, high grade.