Introduction:

Treatment options that are safe, bladder preserving, and effective for patients with BCG-unresponsive HR NMIBC are limited. TAR-200, a novel targeted releasing system, is designed to provide sustained release of gemcitabine in the bladder over many days. SunRISe-1 (SR-1; NCT04640623) is an ongoing, phase 2b study assessing the efficacy and safety of TAR-200 + cetrelimab (anti-PD1) (Cohort 1 [C1]), TAR-200 alone (C2), or cetrelimab alone (C3) in patients with BCG-unresponsive HR NMIBC ineligible for or refusing radical cystectomy. TAR-200 alone is also being assessed in patients with papillary disease only (C4). Preliminary results showed a promising complete response (CR) rate of 83% and durable responses in patients with BCG-unresponsive HR NMIBC treated with TAR-200 (Jacob et al. AUA 2024). We report additional results on the safety and tolerability of TAR-200 monotherapy in C2.

Methods:

Institutional review board approval and informed consent were obtained for this study. Patients aged ≥18 years with histologically confirmed carcinoma in situ (CIS) ± papillary disease (high-grade Ta, any T1), Eastern Cooperative Oncology Group performance status of 0-2, and persistent or recurrent HR NMIBC with last dose of BCG ≤12 months prior to CIS diagnosis were eligible for C1-3. TAR-200 was dosed every 3 weeks through Week 24, then every 12 weeks until Week 96. The primary end point of the SR-1 trial is CR rate at any time; secondary end points reported included duration of response, safety, and tolerability.

Results:

As of May 13, 2024, 85 patients with CIS (median age, 71 years; range, 40-88; concomitant papillary disease, 33%) received TAR-200 monotherapy. The CR rate was 84% (n=85). TAR-200 insertion success rate was 99%, and median indwelling duration was 22 days (range, 5-26). 71 of 85 patients (84%) reported treatment-related adverse events (TRAEs). The majority of TRAEs were grade (Gr) 1-2 lower urinary tract symptoms. The most common TRAEs (≥10%) were pollakiuria (39%), dysuria (35%), urinary tract infection (20%), micturition urgency (18%), and hematuria (14%). The median duration of all TRAEs that had recovered/resolved was 22 days (IQR, 8-112). 8 patients (9%) had Gr 3-4 TRAEs; 5 (6%) had serious TRAEs. 5 patients (6%) had TRAEs that led to treatment discontinuation; these included noninfective cystitis (n=3; 1 Gr1, 2 Gr2), pollakiuria (n=1, Gr2), and urinary retention (n=1, Gr2), within 4.8 months of starting treatment. No treatment-related deaths occurred.

Conclusion:

TAR-200 monotherapy was well tolerated in SR-1, with a high rate of insertion success and a median indwelling duration of 22 days. Commonly reported lower urinary tract related TRAEs were manageable and resolved after a short duration. TAR-200 has a promising safety and efficacy profile as a local, bladder-sparing treatment in HR NMIBC unresponsive to BCG. These results support the continued investigation of TAR-200 in BCG-unresponsive HR NMIBC.

Funding: Janssen Research & Development, LLC, a Johnson & Johnson company