Dr Daneschmand on Data From SunRISe-1 With TAR-200 and Cetrelimab in BCG-Unresponsive NMIBC

Sia Daneshmand MD, professor of Urology, Keck School of Medicine, University of Southern California, discusses preliminary results from the phase 2 SunRISe-1 trial (NCT04640623) in patients with non–muscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guérin (BCG).

TAR-200 is a novel intravesical drug delivery system that leads to sustained local release of gemcitabine into the bladder, and cetrelimab is a PD-1 inhibitor. When combined, these agents may display synergistic activity, thereby improving outcomes in patients with high-risk NMIBC unresponsive to intravesical BCG.

In the trial, TAR-200 was administered every 3 weeks for 24 weeks, then every 12 weeks until week 96. Cetrelimab was administered through week 78. Cystoscopy, urine cytology, CT/MRI, and transurethral resection of bladder tumor were done at baseline and prespecified time points to evaluate response. The primary end point of the study is complete response (CR) rate at any time point. Secondary end points include duration of response, overall survival, pharmacokinetics, quality of life, safety, and tolerability.

The study enrolled patients who are ineligible for or decline radical cystectomy. Data from cohorts 2 and 3, which were presented at the 2023 AUA Annual Meeting, were encouraging, according to Daneschmand. The combination arm (cohort 1) did not have enough evaluable patients for analysis, Daneschmand says. In total, 22 patients received TAR-200 in cohort 2; 73% of these patients achieved CR. Among the patients who received cetrelimab, the CR rate was 38%, which is in line with expectations of response for single-agent checkpoint inhibition in this setting, Daneschmand says, citing the phase 2 KEYNOTE-057 trial (NCT02625961), which demonstrated a CR rate of 41% with pembrolizumab (Keytruda) in patients with BCG-unresponsive, high-risk, NMIBC with carcinoma in situ. 

Regarding safety, 11 patients (85%) in cohort 2 and 8 (62%) in cohort 3 had treatment-emergent adverse effects (TEAEs), most of which were grade 1/2. The most common TEAEs were pollakiuria (39%), micturition urgency (39%), and noninfective cystitis (39%) in cohort 2, and fatigue (23%) and lipase increased (23%) in cohort 3. One patient (8%) in cohort 2 and 2 patients (15%) in cohort 3 had grade 3 treatment-related, TEAEs. One serious TEAE of myocarditis occurred in cohort 3.