Multinational phase 2 study of neoadjuvant cetrelimab with or without TAR-200 for muscle-invasive bladder cancer

Standard of care for muscle-invasive bladder cancer (MIBC) is neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy (RC). However, many patients are ineligible for or refuse cisplatin. The multinational phase 2 SunRISe-4 evaluated neoadjuvant cetrelimab (anti-PD-1) with or without the gemcitabine intravesical system TAR-200 followed by RC in patients with MIBC. Adult patients with ECOG performance status 0 or 1 and cT2-T4a N0M0 MIBC who were ineligible/refusing cisplatin and planned for RC were randomized (5:3) to neoadjuvant cetrelimab plus TAR-200 (cohort 1) or cetrelimab monotherapy (cohort2). Primary endpoint was pathologic complete response (pCR) at RC. pCR was 38% in cohort 1 and 28% in cohort 2; pathologic overall response was 53% versus 44%, and 1-year recurrence-free survival rates were 77% versus 64%. Urinary tumor DNA status before RC and utDNA clearance correlated with pCR, and ctDNA-negative status at baseline and week 12 was associated with longer RFS compared with ctDNA-positive status at the same timepoint. The authors conclude that addition of TAR-200 to neoadjuvant cetrelimab was associated with improved pCR, pOR, and 1-year RFS rate among patients with MIBC.