Introduction:

Patients with Bacillus Calmette–Guérin (BCG)-unresponsive high-risk non–muscle-invasive bladder cancer (HR NMIBC) have limited bladder-sparing treatment options and are at high risk of disease recurrence and progression. Standard of care for BCG-unresponsive HR NMIBC is radical cystectomy (RC), which is associated with significant morbidity and mortality rates and negative impact on quality of life. Consequently, there exists a persistent need for tolerable and effective bladder-sparing therapies for this population. Gemcitabine intravesical system (TAR-200) is a novel intravesical drug-releasing system designed to provide sustained delivery of gemcitabine in the bladder. SunRISe-1 (NCT04640623) is an ongoing phase 2b parallel-cohort study assessing TAR-200 in patients with BCG-unresponsive HR NMIBC who were ineligible for or refused RC. We report recurrence, progression, and time to cystectomy analyses in patients receiving TAR-200 monotherapy (Cohort 2).

Methods:

Patients enrolled in Cohort 2 (≥18 years; ECOG performance status 0-2) had histologically confirmed carcinoma in situ (CIS) with or without papillary disease (high-grade Ta, any T1), after adequate BCG, with last BCG dose ≤12 months from CIS diagnosis. TAR-200 was dosed Q3W through Month 6, then Q12W until Month 24. The primary end point was centrally confirmed overall complete response (CR) rate. Secondary end points included duration of response (DOR), overall survival, and safety and tolerability. Disease-response assessments included cystoscopy and centrally assessed urine cytology Q12W for up to 2 years then Q24W in year 3 until end of study, centrally assessed biopsy at Weeks 24 and 48 or as clinically indicated, and local imaging Q24W until end of year 3. Patients with centrally assessed disease recurrence or progression were staged based on TNM classification by the investigator. Subsequent therapies, including RC, were reported for all patients, as applicable.

Results:

As of the March 31, 2025, data cutoff, 85 patients (median age, 71.0 years [range, 40-88]; 80.0% male; 32.9% with concurrent papillary disease) received TAR-200 monotherapy. Overall, among 85 patients, 70 achieved CR, leading to a CR rate of 82.4%. The median follow-up was 20.2 months (range, 2-48). 37/70 responders (52.9%) had DOR of ≥12 months (Table). Thirty-seven responders remained in CR at data cutoff, including 33 with ongoing responses (47.1%) and 4 who were permanently censored. 41/85 patients had disease persistence, progression, or recurrence, of whom 30 were responders. Of the 41 patients, the majority had persistence or recurrence of HR NMIBC (CIS/Ta/T1). Progression to T2 or higher disease (any N+/M+) was observed in 7 patients (8.2%) (Table), including 1 with metastatic disease. There were 7 deaths (unrelated to treatment). 18/85 patients (21.2%) had RC. The estimated 12- and 24-month RC-free rates were 86.6% and 75.5%, respectively.

Conclusion:

SunRISe-1 Cohort 2 results show that TAR-200 monotherapy is associated with a high CR rate and durable responses, with minimal risk of disease progression to a more advanced (T2 or higher) disease stage, and a potential delay to RC. This low rate of progression compares favorably with historical progression rates of ~20% with standard of care in patients with HR NMIBC CIS. These results support TAR-200 as a novel bladder-sparing treatment option for patients with BCG-unresponsive CIS with or without papillary disease.

Funding: Johnson & Johnson