Design and implementation of a patient-centric expanded access program with cretostimogene grenadenorepvec in non-muscle invasive bladder cancer unresponsive to bacillus Calmette-Guerin.

TPS897 Background: Current guidelines recommend radical cystectomy for High-Risk, BCG-Unresponsive Non-Muscle Invasive Bladder Cancer (HR BCG-UR NMIBC). However, many patients are unwilling or unfit for this intervention due to medical risks. Thus, there is a need for effective, well-tolerated, and accessible bladder-sparing treatments. Cretostimogene grenadenorepvec is an oncolytic immunotherapy with dual mechanisms of action. It replicates in and lyses cancer cells with Retinoblastoma (Rb)-E2F pathway alterations, while simultaneously amplifying an anti-tumor immune response, further mediated by the GM-CSF transgene. Results from the Phase 3 BOND-003 study led to cretostimogene receiving Fast Track and Breakthrough Therapy Designations by the US FDA for BCG-UR NMIBC with CIS. The cretostimogene Expanded Access Program (CRETO-EAP) (NCT06443944) an open-label, expanded access clinical trial provides cretostimogene to real-world patients who may not qualify for current clinical trials or are unable to access or tolerate currently available options. Methods: The eligibility criteria are pragmatic and inclusive of the at-risk population seen in real-world practice: ECOG PS 0-3, pathologically confirmed BCG-UR CIS +/- Ta/T1 after completion of adequate BCG treatment. The protocol has been amended to improve flexibility and include patients who received prior therapies for HR BCG-UR NMIBC, including investigational agents. Intravesical cretostimogene is administered 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 biannually through Month 24. Re-induction is permitted. Additionally, patients with partial response, defined as persistent but improved disease at Week 25 or subsequent timepoints, may receive continued 3-weekly doses of cretostimogene at the discretion of the investigator. As per routine NMIBC surveillance, primary disease assessments include serial cystoscopy, urine cytology, axial imaging, and bladder biopsies when clinically indicated, with pathologic samples reviewed locally. Co-primary endpoints include safety and complete response at any time. The incidence of adverse events will be reported using the Medical Dictionary for Regulatory Activities (MedDRA) and CTCAE v5.0. Secondary outcomes include Duration of Response, Progression-Free Survival, Cystectomy-Free Survival, Patient Reported Outcomes and Health-Related Quality of Life measures. A broad cross-section of geographically diverse clinical sites that serve socioeconomically diverse patients has been identified. The study is actively enrolling, with initial patients treated. Clinical trial information: NCT06443944 .