Introduction and objective
Patients (pts) with high-risk non–muscle-invasive bladder cancer (HR NMIBC) unresponsive to intravesical BCG have limited treatment (tx) options. TAR-200 is a novel intravesical drug delivery system that provides sustained local release of gemcitabine into the bladder. Cetrelimab (CET) is an anti-PD1 agent. SunRISe-1 is an ongoing ph 2 study evaluating efficacy and safety of TAR-200 + CET (Cohort 1 [C1]), TAR-200 alone (C2), or CET alone (C3) in BCG-unresponsive pts with HR NMIBC (carcinoma in situ [CIS]) who are ineligible for or decline radical cystectomy. We report preliminary results from SunRISe-1, providing data from C2 and C3.
Pts ≥18 y with histologically confirmed CIS±papillary disease (T1, high-grade Ta) who completed adequate BCG ≤12 mo before enrollment and with ECOG performance status 0-2 were randomized to C1, C2, or C3. TAR-200 was dosed Q3W through Wk 24, then Q12W until Wk 96. CET was dosed through Wk 78. Cystoscopy, centrally read urine cytology, CT/MRI, and TURBT (bladder biopsy) were done at baseline and prespecified time points to assess disease response. The primary end point is overall complete response (CR) rate at any time point. Secondary end points include duration of response (DOR), overall survival, PK, quality of life, safety, and tolerability. Initial results are reported; updated data (≈40 pts) will be included in the presentation.
As of data cutoff (May 25, 2022), 13 pts in C2 and 13 in C3 (median 71.5 y [range 51-88]) received tx. Efficacy evaluable set: 8 pts in C2, 8 in C3. Centrally confirmed CR by urine cytology and/or biopsy was 88% (95% CI 47-100) in C2 and 38% (9-76) in C3. Median CR duration of response for C2 and C3 was not reached after median follow-up of 13.6 and 12.0 wks, respectively. At data cutoff, 7 of 8 pts in C2 remained CR, with 3 ongoing responses ≥6 mo (range 7.7-9.4 mo). 11 pts (85%) in C2 and 8 (62%) in C3 had tx-emergent adverse events (TEAEs); most were Gr 1-2. The most common TEAEs were pollakiuria (39%), micturition urgency (39%), and noninfective cystitis (39%) in C2; fatigue (23%) and lipase increased (23%) in C3. 1 pt (8%) in C2 and 2 pts (15%) in C3 had tx-related Gr ≥3 TEAEs. 1 serious TEAE (myocarditis) occurred in C3.
First results from SunRISe-1 show promising CR rate and safety profile with TAR-200 monotherapy, and CET results are consistent with other anti-PD(L)1 tx in this setting. Preliminary efficacy and safety data support the continued study in NMIBC.