Expanded access program of cretostimogene grenadenorepvec in patients with non-muscle invasive bladder cancer unresponsive to bacillus Calmette-Guerin.

TPS902 Background: The current American Urological Association (AUA) guideline recommendation for patients diagnosed with High-Risk, BCG-Unresponsive Non-Muscle Invasive Bladder Cancer (HR BCG-UR NMIBC) is 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 HR BCG-UR NMIBC. Cretostimogene grenadenorepvec is an oncolytic immunotherapy with a dual mechanism of action. It selectively replicates and lyses bladder cancer cells with Retinoblastoma (Rb)-E2F pathway alterations. The subsequent release of virus- and tumor- specific antigens initiate antitumor immune activation amplified by the GM-CSF transgene, a potent cytokine. Based upon preliminary efficacy and safety results from the ongoing Phase 3 BOND-003 study, cretostimogene received both Fast Track and Breakthrough Therapy Designations by the US FDA for BCG-UR NMIBC with CIS indication. The cretostimogene Expanded Access Program (EAP) ( NCT06443944 ) is an open-label, compassionate use clinical trial designed to provide cretostimogene to a diverse population of real-world patients with BCG-UR NMIBC with CIS who may not otherwise be eligible for currently enrolling clinical trials. Methods: Pragmatic real-world eligibility criteria include: age ≥18 years, ECOG performance status of 0-3, pathologically confirmed BCG-UR CIS +/- HG Ta/T1 disease after completion of adequate BCG treatment, as defined by the US FDA. Patients will receive intravesical cretostimogene 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 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 at 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. The study is open and actively recruiting. Clinical trial information: NCT06443944 .