Pts with BCG-unresponsive HR NMIBC are at high risk of disease progression with limited treatment (tx) options. TAR-200, an intravesical drug delivery system, provides sustained release of gemcitabine in the bladder over many days. SunRISe-1 (NCT04640623) is an ongoing, randomized, ph 2b study assessing efficacy and safety of TAR-200 + cetrelimab (anti-PD1) (Cohort 1 [C1]), TAR-200 alone (C2), or cetrelimab alone (C3) in pts with BCG-unresponsive HR NMIBC ineligible for or refusing radical cystectomy. We report results from C2.
Eligible pts aged ≥18 y had histologically confirmed carcinoma in situ (CIS) ± papillary disease (high-grade Ta, any T1), ECOG performance status 0-2, and persistent or recurrent HR NMIBC with last dose of BCG ≤12 mo prior to CIS diagnosis. TAR-200 was dosed Q3W through Wk 24, then Q12W until Wk 96. Response assessments: cystoscopy and centrally assessed urine cytology, CT/MRI, and bladder biopsy (at Wk 24, 48, and as clinically indicated). Primary end point: overall complete response (CR) rate. Secondary end points: duration of response (DOR), overall survival, safety, and tolerability.
At 24 Aug 2023 data cutoff, 54 pts (median age, 71 y; range, 40-85; 33% with concurrent papillary disease) received TAR-200 monotherapy. 30 pts were efficacy evaluable. Centrally confirmed CR by urine cytology and/or biopsy was achieved in 23/30 pts (77%; 95% CI, 58-90). Median DOR was not reached (median follow-up in responders, 48 wks; range, 12-121); 21/23 responders remain in CR with 11/11 and 6/6 having response ≥6 mo and ≥12 mo from CR, respectively. CR rate by investigator assessment was comparable with central results. 29 pts (54%) had tx-related adverse events (TRAEs); most common (≥10%) were pollakiuria, dysuria, and micturition urgency. 4 pts (7%) had Gr ≥3 TRAEs; 1 (2%) had serious TRAE; 2 (4%) had TRAEs leading to discontinuation. No deaths were reported.
In SunRISe-1, TAR-200 monotherapy is associated with an unprecedented CR rate, durable responses, and a favorable tolerability profile in pts with BCG-unresponsive CIS, supporting its continued investigation in HR NMIBC.