Cretostimogene grenadenorepvec (a BCG-unresponsive intravesical oncolytic immunotherapy) produced complete responses in three-quarters of patients in the phase III BOND-003 cohort C trial for high-risk, BCG-unresponsive non–muscle-invasive bladder cancer with carcinoma in situ, according to results reported in The Lancet Oncology. The international, single-arm study enrolled 115 patients across 41 centers, with 83 of 110 patients (75%) achieving a centrally confirmed complete response at any time after a median follow-up of 25.8 months. The report notes that 14 complete responses occurred after re-induction, and that 46% remained in complete response at 12 months and 42% at 24 months. Safety was described as predominantly mild and transient, with dosing administered intravesically once weekly for six weeks, optional second induction for persistent disease at three months, and maintenance for responders. Mechanistically, the therapy is designed to selectively replicate in tumors with retinoblastoma–E2F pathway alterations while stimulating antitumor immunity. For the bladder cancer field, the data place grenadenorepvec in a new evidentiary footing for a population that historically has limited options after BCG failure, potentially reshaping treatment pathways toward immune-activating intravesical approaches that aim to delay or avoid cystectomy.