(UroToday.com) The 2025 Western Section AUA annual meeting featured a urothelial carcinoma session and a presentation by Anne K. Schuckman, MD, discussing streamlined, patient-centric design of the cretostimogene grenadenorepvec expanded access program in patients with non-muscle invasive bladder cancer unresponsive to BCG. Current guidelines recommend radical cystectomy for high-risk BCG-unresponsive non-muscle invasive bladder cancer. 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, an oncolytic immunotherapy, selectively replicates in and lyses cancer cells with Retinoblastoma-E2F pathway alterations, releasing antigens that trigger antitumor immune activation, enhanced by the GM-CSF transgene:
The BOND-003 trial (cretostimogene in BCG unresponsive non-muscle invasive bladder cancer with CIS) demonstrated a 75% complete response and median duration of response of 27.9 months, with 0% Grade 3+ treatment-related adverse events. These results led to cretostimogene receiving Fast Track and Breakthrough Therapy Designations by the US FDA for BCG-unresponsive non-muscle invasive bladder cancer. The Cretostimogene expanded Access Program (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.
The eligibility criteria are pragmatic and inclusive of the at-risk population seen in real-world practice: ECOG performance status 0-3, pathologically confirmed BCG-unresponsive 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 high-risk BCG-unresponsive non-muscle invasive bladder cancer, including investigational agents. Intravesical cretostimogene will be 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 time points, may receive continued 3-weekly doses of cretostimogene at the discretion of the investigator:
As per routine non-muscle invasive bladder cancer surveillance, primary disease assessments include serial cystoscopy, urine cytology, axial imaging, and bladder biopsies when clinically indicated, with pathologic samples reviewed locally. The co-primary endpoints include safety and complete response at any time. Secondary endpoints include duration of response, progression-free survival, cystectomy-free survival, patient-reported outcomes, and health-related quality of life. The incidence of adverse events will be reported using the Medical Dictionary for Regulatory Activities (MedDRA) and CTCAE v5.0. A broad cross-section of geographically diverse clinical sites that serve socioeconomically diverse patients has been identified. The study is actively recruiting patients, and the first patients have been treated.
Presented by: Anne K. Schuckman, MD, University of Southern California, Los Angeles, CA
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 Western Section American Urological Association (AUA) Annual Meeting, Napa Valley, CA, Sun, Nov 2 – Thurs, Nov 6, 2025.