BACKGROUND:
Patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (HR NMIBC) are at high risk of disease progression and have limited bladder-sparing treatment options. TAR-200, an intravesical drug delivery system, is designed to provide sustained release of gemcitabine in the bladder over 3 weeks. SunRISe-1 (NCT04640623) is an ongoing, randomized, phase 2b study assessing the efficacy and safety of TAR-200 + cetrelimab (anti-PD1) (Cohort 1), TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3) in patients with BCG-unresponsive HR NMIBC with carcinoma in situ (CIS), with or without papillary disease, who are ineligible for or refuse radical cystectomy. As of Amendment 4, TAR-200 alone is also being assessed in patients with papillary disease only (Cohort 4). We report results from Cohort 2.
METHODS:
Eligible patients aged ≥18 years had histologically confirmed CIS ± papillary disease (high-grade Ta, any T1) after adequate BCG, with the last dose of BCG ≤12 months prior to CIS diagnosis, and an Eastern Cooperative Oncology Group performance status of 0-2. TAR-200 was dosed every 3 weeks through Week 24, then every 12 weeks until Week 96. Response was assessed by cystoscopy and centrally assessed urine cytology, computed tomography/magnetic resonance imaging, and bladder biopsy (at Weeks 24, 48, and as clinically indicated). The primary end point was overall complete response (CR) rate. Secondary end points included duration of response (DOR), overall survival, safety, and tolerability.
RESULTS:
At data cutoff (Jan 2, 2024), 85 patients (median age, 71 years; range, 40-88; 33% with concurrent papillary disease) received TAR-200 monotherapy. 58 patients were efficacy evaluable. Centrally confirmed CR rate was 83% (95% CI, 71-91) by urine cytology and/or biopsy. The estimated 1-year DOR rate is 75% (95% CI, 50-88), with a median follow-up in responders of 30 weeks (range, 14-140); 41 of 48 responders (85%) remain in CR at data cutoff. 47 of 48 (98%) CRs were achieved at first disease assessment at Week 12. CR rate by investigator assessment (86%; 95% CI, 75-94) correlated strongly with central results. 61 patients (72%) had treatment-related adverse events (TRAEs); most common (≥10%) were pollakiuria (35%), dysuria (29%), micturition urgency (15%), and urinary tract infection (15%). 7 patients (8%) had grade ≥3 TRAEs, 4 (5%) had serious TRAEs, and 4 (5%) had TRAEs leading to discontinuation. No treatment-related deaths were reported.
CONCLUSIONS:
In SunRISe-1, TAR-200 monotherapy is associated with a clinically meaningful, high, centrally confirmed CR rate, durable responses, and a favorable benefit-risk profile in patients with BCG-unresponsive CIS.
