Multinational phase 3 trial of intravesical cretostimogene grenadenorepvec in high-risk, BCG-unresponsive NMIBC with carcinoma in situ

Prof. Mark Tyson

Cretostimogene grenadenorepvec (‘cretostimogene’) is an oncolytic immunotherapy that replicates in and lyses cancer cells with retinoblastoma-E2F pathway alterations and amplifies the immune response. The single-arm phase 3 BOND-003 Cohort C study, done in 41 centers located in North America, Asia, and Australia evaluated the response and safety/tolerability of intravesical cretostimogene in patients with high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ. The study enrolled 112 adult patients with ECOG performance status 0-2 who received cretostimogene. The primary endpoint was centrally confirmed complete response at any time in patients who completed 3-month assessment. After a median follow-up of 25.8 months (IQR 22.1-33.1), complete response at any time was observed in 83 of 110 patients (75%; 95% CI 66.3-83.2). At least one treatment-related adverse event was observed in 71 of 112 patients (63%), the most common being bladder spasm (25%), pollakiuria (22%), and micturition urgency (21%); there were no grade 3 or higher TRAEs and no treatment-related discontinuations. Two patients had serious TRAEs; both grade 2. The authors conclude that cretostimogene showed clinically meaningful antitumor response, with an adverse event profile characterized predominantly by low-grade, transient events. Cretostimogene shows promise as an innovative bladder-sparing treatment for high-risk, BCG-unresponsive, NMIBC with carcinoma in situ.