(UroToday.com) The 2024 SUO annual meeting included a urothelial carcinoma session, featuring a presentation by Dr. Sarah Psutka discussing the cretostimogene grenadenorepvec expanded access program in patients with non-muscle invasive bladder cancer (NMIBC) unresponsive to BCG. The current AUA Guidelines recommend that patients diagnosed with BCG-unresponsive high risk NMIBC undergo radical cystectomy.
However, many patients are unwilling to undergo a radical cystectomy 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-unresponsive high risk NMIBC. Cretostimogene grenadenorepvec is an oncolytic immunotherapy designed to selectively replicate in bladder cancer cells with Rb-E2F pathway alterations, commonly found in BCG-unresponsive high risk NMIBC. The dual mechanism of action of cretostimogene is as follows:
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-unresponsive high risk 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-unresponsive high risk NMIBC who may not otherwise qualify or have access to clinical trials:
Pragmatic real-world eligibility criteria include the following:
- Age ≥ 18 years
- ECOG performance status of 0-3
- Pathologically confirmed BCG-unresponsive 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 with the following study administration schedule:
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 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
- 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, and the first patients in the EAP program have been enrolled.
Presented by: Sarah Psutka, MD, MSc, University of Washington, Seattle, WA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 Society of Urologic Oncology (SUO) Annual Meeting, Dallas, TX, Tues, Dec 3 – Fri, Dec 6, 2024.