This parallel cohort study enrolled patients with BCG-unresponsive carcinoma in situ (CIS) with or without papillary disease across four cohorts. The primary analysis focused on TAR-200 monotherapy in patients with CIS (Cohort 2, n=85) and disease-free survival in high-risk papillary disease-only patients (Cohort 4, n=52). Additional cohorts examined TAR-200 plus cetrelimab (Cohort 1, n=53) and cetrelimab monotherapy (Cohort 3, n=28). TAR-200 was administered every 3 weeks through month 6, then every 12 weeks through month 24, with cetrelimab given intravenously every 3 weeks through month 18.
The study demonstrated remarkable efficacy for TAR-200 monotherapy in BCG-unresponsive CIS. The centrally confirmed complete response (CR) rate was 82.4% (95% CI, 72.6 to 89.8), representing the highest single-agent CR rate reported to date in this setting. The median duration of response was 25.8 months (95% CI, 8.3 to not estimable), with 52.9% of responders maintaining response for ≥12 months. CR rates at 3, 6, and 12 months were 78.8% (95% CI, 68.6 to 86.9), 58.8% (95% CI, 47.6 to 69.4), and 45.9% (95% CI, 35.0 to 57.0), respectively. In the papillary disease-only cohort, disease-free survival rates at 6, 9, and 12 months 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.
TAR-200 monotherapy demonstrated superior tolerability compared to combination therapy. Grade ≥3 treatment-related adverse events occurred in 12.9% of CIS patients and 13.5% of papillary disease-only patients receiving TAR-200 monotherapy, compared to 37.7% in the TAR-200 plus cetrelimab cohort. Most adverse events were low-grade urinary tract symptoms, including pollakiuria (43.5%), dysuria (40.0%), and micturition urgency (24.7%) that resolved after a median of 3.0 weeks. Serious treatment-related adverse events occurred in 5.9% and 5.8% of patients in the TAR-200 monotherapy cohorts, respectively. Only 3.5% of CIS patients and 7.7% of papillary disease-only patients discontinued TAR-200 due to treatment-related adverse events. The safety profile of combination therapy was less favorable, with 15.1% of patients experiencing serious treatment-related adverse events and higher discontinuation rates of 26.4% for TAR-200 and 24.5% for cetrelimab. Cetrelimab monotherapy showed a CR rate of 46.4% (95% CI, 27.5 to 66.1) with grade ≥3 treatment-related adverse events in 7.1% of patients. The overall survival rates at 6 and 12 months were 98.7% (95% CI, 91.2 to 99.8) and 94.7% (95% CI, 86.5 to 98.0) for TAR-200 monotherapy in CIS patients, with no treatment-related deaths across any cohort.
The study represents a significant advancement in BCG-unresponsive NMIBC treatment, demonstrating that TAR-200 monotherapy achieves unprecedented response rates with durable efficacy and manageable toxicity. Limitations include the single-arm design, modest sample sizes, and relatively short follow-up duration. The results support TAR-200 monotherapy as a promising bladder-sparing option to delay or avoid radical cystectomy in patients with BCG-unresponsive high-risk NMIBC. In the future, head-to-head comparisons of different intravesical options for patients with high-risk NMIBC will be needed to establish the best sequencing strategy for these regimens.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
References:
- Daneshmand S, Van der Heijden MS, Jacob JM, Guerrero-Ramos F, Bögemann M, Simone G, et al. TAR-200 for Bacillus Calmette-Guérin–Unresponsive High-Risk Non–Muscle-Invasive Bladder Cancer: Results From the Phase IIb SunRISe-1 Study. J Clin Oncol. 2025;00:1-11. DOI: https://doi.org/10.1200/JCO-25-01651.