Dr Dinney on the Association Between UGDB and Cretostimogene Grenadenorepvec Response in NMIBC

"[Urinary genomic disease burden] is a very sensitive biomarker for the presence of disease, more sensitive than other tests that we used [in the past], such as cytology."

Colin P.N. Dinney, MD, chairman and W.A. "Tex" & D. Moncrief, Jr. Distinguished Chair in Urology of the Department of Urology in the Division of Surgery, and co-chair of the Genitourinary Steering Committee - Bladder Task Force, at The University of Texas MD Anderson Cancer Center, discussed the clinical implications of using urinary genomic disease burden (UGDB) as a potential biomarker for assessing therapeutic response to cretostimogene grenadenorepvec in patients with non–muscle-invasive bladder cancer (NMIBC).

Cretostimogene grenadenorepvec is an investigational oncolytic immunotherapy designed to selectively replicate in bladder cancer cells with RB/E2F pathway alterations. Upon replication and lysis of tumor cells, virus- and tumor-specific antigens are released, initiating antitumor immune responses that are further amplified by the granulocyte macrophage colony–stimulating factor transgene contained within the viral construct.

According to Dinney, UGDB appears to be a highly sensitive marker for the presence of disease, which could offer greater sensitivity compared with traditional tests such as urine cytology. He emphasized that if genomic alterations detected in urine samples disappear following treatment, it strongly suggests that the cancer has likely been eradicated. This correlation between genomic clearance and disease control may offer a non-invasive means of dynamically assessing treatment efficacy in clinical practice.

In a poster presentation at the 2025 AUA Annual Meeting, Dinney and colleagues presented findings from a translational analysis of the phase 3 BOND-003 (NCT04452591) and phase 2 CORE-001 (NCT04387461) trials, which showed that minimal residual disease status was strongly correlated with 12-month recurrence-free survival (RFS) in patients with BCG-unresponsive, high-risk NMIBC treated with cretostimogene grenadenorepvec.

Potential future directions for cretostimogene grenadenorepvec include further validation of UGDB as a surrogate marker for long-term outcomes such as RFS and overall survival, Dinney stated. Incorporating this biomarker into ongoing and future clinical trials of cretostimogene grenadenorepvec could support adaptive treatment strategies, enabling clinicians to tailor therapy based on early molecular response. Additionally, monitoring urinary genomic changes could help identify patients who may benefit from intensified therapy or alternative approaches if early clearance is not achieved, he explained.