Dr Martini on the Mechanism of Action of Cretostimogene Grenadenorepvec in Urothelial Carcinoma

“Cretostimogene is a gene therapy [that uses] a viral vector which is an adenovirus which is oncolytic.”

Alberto Martini, MD, a urologic oncologist at the University of Cincinnati Medical Center and an assistant professor of clinical urology at the University of Cincinnati College of Medicine, discussed the investigational oncolytic therapy cretostimogene grenadenorepvec for the treatment of patients with urothelial carcinoma.

Cretostimogene is a gene therapy which uses an oncolytic adenovirus viral vector, Martini began. This virus is able to selectively replicate in RB-E2F–altered bladder cancer cells, resulting in subsequent tumor cell lysis, he added. This mechanism of action also activates the transgene of the granulocyte colony-stimulating factor, which in turn triggers an immune response, he concluded.

Cretostimogene was evaluated in patients with intermediate-risk non–muscle-invasive bladder cancer (NMIBC) following transurethral resection of bladder tumor (TURBT) in the phase 3 PIVOT-006 trial (NCT06111235). The study randomly assigned patients 1:1 to receive either cretostimogene after TURBT or surveillance after TURBT. The primary end point is recurrence-free survival (RFS). RFS at 12 and 24 months represents a secondary end point of the study; safety is also a secondary end point. In September 2025, the study completed enrollment.

Cretostimogene was also examined in patients with BCG-unresponsive NMIBC in the phase 3 BOND-003 trial (NCT04452591). Findings presented during the 2025 American Urological Association Annual Meeting revealed that cretostimogene monotherapy produced an any-time complete response (CR) rate of 75.5%. The 12- and 24-month CR rates were 46.4% (95% CI, 36.9%-56.1%) and 33.7% (95% CI, 24.8%-43.8%), respectively. At the data cutoff of March 14, 2025, the median duration of response was 28 months and was ongoing. Most patients (97.3%) were free from progression to muscle-invasive disease at 24 months. Thirty-four patients had confirmed CRs at 24 months; 24-month assessments were pending for 9 patients at the data cutoff.