Cretostimogene grenadenorepvec (RB–E2F–selective oncolytic virus) drives 75% CR with near-zero severe toxicity in BCG-unresponsive CIS NMIBC

Cretostimogene grenadenorepvec is an intravesical, replication-competent oncolytic immunotherapy that preferentially replicates in and lyses tumor cells with retinoblastoma–E2F pathway alterations while also boosting antitumor immunity. In the international, single-arm Phase 3 BOND-003 Cohort C trial (NCT04452591) in high-risk, BCG-unresponsive NMIBC with CIS ± resected HG Ta/T1 (n=112 treated; 110 evaluable for the primary endpoint; median age 74), centrally confirmed complete response (CR) at any time was 75% (83/110; 95% CI 66.3-83.2) at a June 23, 2025 data cutoff with median follow-up 25.8 months. Safety looked unusually clean for this setting: 63% had any treatment-related AE (mostly bladder spasm 25%, pollakiuria 22%, urgency 21%), there were no Grade 3/4 TRAEs, no treatment-related discontinuations or deaths, and 2% had serious TRAEs (both Grade 2); by comparison, FDA-approved bladder-sparing options in this population include intravesical nadofaragene firadenovec (3‑mo CR 53.4%; median CR duration ~9.7 months; ~24% high-grade–recurrence-free at 12 months) and systemic pembrolizumab (KEYNOTE-057; ~41% 3‑mo CR), with radical cystectomy still the guideline “definitive” standard for eligible patients.