Introduction:

The current American Urological Association (AUA) Guidelines recommend that patients diagnosed with BCG-Unresponsive High-Risk Non-Muscle Invasive Bladder Cancer (BCG-UR HR NMIBC) undergo radical cystectomy. However, many patients are unwilling to undergo such a morbid intervention or are unfit due to competing medical risks. Therefore, a considerable unmet medical need exists for clinically effective, well-tolerated, and readily available bladder-sparing treatment options for patients with BCG-UR HR NMIBC. Cretostimogene grenadenorepvec is an oncolytic immunotherapy designed to selectively replicate in bladder cancer cells with Retinoblastoma (Rb)-E2F pathway alterations, commonly found in BCG-UR HR NMIBC. Based upon preliminary efficacy and safety results from the ongoing Phase 3 BOND-003 study, cretostimogene has received Fast Track and Breakthrough Therapy Designations by the US FDA for the BCG-UR NMIBC with CIS indication. The cretostimogene Expanded Access Program (EAP) is an open-label, expanded access clinical trial designed to provide cretostimogene to a diverse population of real-world patients with BCG-UR NMIBC who may not otherwise qualify or have access to clinical trials.

Methods:

Pragmatic real-world eligibility criteria: age ≥18 years, ECOG performance status of 0-3, pathologically confirmed BCG-UR CIS +/- HG Ta or HG T1 disease after completion of adequate BCG treatment, as defined by the US FDA. Patients will receive intravesical cretostimogene in combination with DDM, a transduction agent, for six weekly doses during the induction phase, followed by three weekly maintenance cycles quarterly through Month 12, then every six months through Month 24. Re-induction is permitted. Primary disease assessments include serial cystoscopy, urine cytology, axial imaging, and directed bladder biopsies as clinically indicated with local review of pathologic samples. The primary objective is to evaluate the safety of cretostimogene. The incidence of adverse events will be reported using Medical Dictionary for Regulatory Activities (MedDRA) and CTCAE v5.0. Secondary outcomes include Complete Response at any time and 12 months, Duration of Response, high-grade Recurrence-Free Survival, Progression-Free Survival, and Radical Cystectomy-Free Survival. Exploratory outcome measures include Health-Related Quality of Life, Overall Survival, and biomarker assessments. A broad cross-section of geographically and socioeconomically diverse clinical sites have been identified. First patients have been enrolled. NCT06443944

Results:

Conclusion:

Funding: CG Oncology