TAR-200 for Bacillus Calmette-Guérin–Unresponsive High-Risk Non–Muscle-Invasive Bladder Cancer: Results From the Phase IIb SunRISe-1 Study

PURPOSE TAR-200 is a first-in-class intravesical drug-releasing system designed to provide sustained delivery of gemcitabine in the bladder. TAR-200 alone or in combination with cetrelimab (PD-1 inhibitor) could improve outcomes in patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC) ineligible for or refusing radical cystectomy. METHODS In this phase IIb parallel cohort study, patients with BCG-unresponsive carcinoma in situ (CIS) with/without papillary disease received TAR-200 monotherapy (Cohort 2 [C2]), TAR-200 plus cetrelimab (C1), or cetrelimab monotherapy (C3). Patients with BCG-unresponsive high-risk papillary disease-only NMIBC received TAR-200 monotherapy (C4). TAR-200 was dosed through month 24 and cetrelimab through month 18. Primary end points were centrally confirmed overall complete response (CR) rate (C1-3) or disease-free survival (DFS) rate (C4) (ClinicalTrials.gov number: NCT04640623). RESULTS At data cutoff (March 31, 2025), 53, 85, 28, and 52 patients were treated in C1-4, respectively. In C2, CR rate and median duration of response were 82.4% (95% CI, 72.6 to 89.8) and 25.8 months (95% CI, 8.3 to not estimable), respectively. In C4, 6-, 9-, and 12-month DFS rates were 85.3% (95% CI, 71.6 to 92.7), 81.1% (95% CI, 66.7 to 89.7), and 70.2% (95% CI, 51.6 to 82.8), respectively. In C1 and C3, CR rates were 67.9% (95% CI, 53.7 to 80.1) and 46.4% (95% CI, 27.5 to 66.1), respectively. Rates of grade ≥3 treatment-related adverse events (AEs) were 12.9%, 13.5%, 37.7%, and 7.1% in C2, C4, C1, and C3, respectively, and of serious treatment-related AEs, 5.9%, 5.8%, 15.1%, and 3.6%. No treatment-related deaths occurred. CONCLUSION TAR-200 monotherapy was well tolerated, with a high CR rate, durable responses, and prolonged DFS in patients with BCG-unresponsive high-risk NMIBC. TAR-200 monotherapy offered a more favorable risk-benefit profile versus TAR-200 plus cetrelimab or cetrelimab alone in BCG-unresponsive CIS.