(UroToday.com) The 2025 South Central AUA annual meeting included a session on bladder cancer, featuring a trials in progress presentation from Colin Dinney, MD, discussing updates to the BOND-003 Cohort P trial. Patients presenting with high risk BCG-unresponsive non muscle invasive bladder cancer have limited treatment options.
Currently, the US FDA has approved treatments for BCG-unresponsive patients who harbor CIS. Consequently, a considerable unmet medical need exists for additional clinically effective and well-tolerated bladder-sparing treatment options. This is particularly relevant for the BCG-unresponsive papillary-only population, which may comprise most BCG-unresponsive non muscle invasive bladder cancer patients.
Cretostimogene grenadenorepvec is an oncolytic immunotherapy with a dual mechanism of action. It selectively replicates in and lyses bladder cancer cells with Rb-E2F pathway alterations. The subsequent release of virus- and tumor- specific antigens initiates an antitumor immune activation which is further amplified by the transgene for GM-CSF, a potent cytokine. Cretostimogene has received US FDA Fast Track and Breakthrough Therapy Designations in the high risk BCG-unresponsive non muscle invasive bladder cancer with CIS indication. Based on the strength of these data, the BOND-003 Cohort P study (NCT044552591) was designed as a multi-national, single-arm, clinical trial to assess the efficacy and safety of intravesical cretostimogene in patients with high risk, papillary-only, BCG-unresponsive non muscle invasive bladder cancer.
Eligibility criteria include age ≥18 years, ECOG performance status of 0-2, histologically confirmed BCG-unresponsive HG Ta/T1 papillary disease without CIS within 90 days of study enrollment. Patients who recur with a HG Ta/T1 tumor within six months of the last dose of adequate BCG or who recur with HG T1 after a single induction course of BCG may be eligible. Patients must have no evidence of residual bladder cancer before treatment. Intravesical cretostimogene is instilled in combination with n-dodecyl-β-D-maltoside (DDM), an excipient that enhances adenoviral delivery, for six weekly doses during the induction phase, followed by three weekly maintenance cycles quarterly through month 12, then every six months through month 36:
Re-induction is permitted after the first disease assessment for patients with persistent HG Ta and/or CIS. Primary disease assessments include serial cystoscopy, urine cytology, axial imaging, and mandatory biopsy at month 12, with centralized review of pathologic samples. The primary outcome measure is all-cause event-free survival:
Secondary endpoints include recurrence-free survival, progression-free survival, cystectomy-free survival, bladder cancer-specific survival, safety, and time to next intervention. Exploratory outcome measures include patient-reported quality of life and biomarker analyses. 35+ clinical sites were selected in the United States and Japan, and enrollment is now complete.
Dr. Dinney also presented the initial results of the first 24 treated patients. There was a strong, early response with 90.5% (95% CI 77.9-100) high-grade recurrence-free survival at 3 and 9 months:
The treatment was very well tolerated with no grade 3+ treatment-related adverse events.
Presented by: Colin Dinney, MD, MD Anderson Cancer Center, Houston, TX
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 South Central American Urological Association (AUA) Annual Meeting, Orlando, FL, Wed, Sept 10 – Sat, Sept 13, 2025.