(UroToday.com) The 2025 SUO annual meeting featured a urothelial carcinoma trials in progress session and a presentation by Dr. Trinity Bivalacqua discussing CORE-008 Cohort B evaluating intravesical cretostimogene grenadenorepvec in patients with high risk, BCG exposed non muscle invasive bladder cancer. Patients with high-risk non muscle invasive bladder cancer whose disease trajectory falls outside the strict FDA guidance of BCG unresponsive represent a significant unmet need, often lacking access to clinical trials or evidence-based treatment options.
Cretostimogene grenadenorepvec is a tumor-selective oncolytic immunotherapy with a dual mechanism of action. It replicates in and lyses cancer cells with Retinoblastoma-E2F pathway alterations, releasing virus- and tumor-specific antigens that initiate anti-tumor immune response, further enhanced by the GM-CSF transgene. BOND-003 evaluating cretostimogene in high-risk BCG unresponsive non muscle invasive bladder cancer with CIS showed a 75.5% complete response at any time and a median duration of response of 27.9 months, with 0% grade 3+ treatment related adverse events, consistent with previous findings. Cretostimogene received fast track and breakthrough therapy designations by the US FDA for high-risk BCG unresponsive non muscle invasive bladder cancer with CIS.
The CORE-008 clinical trial (NCT06567743) was developed as a phase 2, multi-arm, multi-cohort trial to evaluate the efficacy and safety of cretostimogene in patients with high-risk non muscle invasive bladder cancer, across BCG naïve, BCG exposed, and BCG unresponsive disease states:
At the 2025 SUO annual meeting, Dr. Bivalacqua and colleagues described Cohort B of CORE-008, which examines the efficacy and safety of cretostimogene in BCG exposed non muscle invasive bladder cancer.
Cohort B eligibility criteria include pathologic confirmation of high-risk non muscle invasive bladder cancer, CIS containing and papillary only, as defined by the AUA/SUO guidelines, and recurrence after prior BCG (BCG exposure). BCG exposed non muscle invasive bladder cancer is defined as:
- High-grade recurrence in patients who are BCG resistant (recurrence after at least 5 of 6 induction doses), or
- Those who experience delayed relapse within 24 months following either adequate BCG (≥5 induction doses plus ≥2 re-induction or maintenance doses) but outside the defined BCG unresponsive window, or
- Following inadequate BCG (3–6 doses)
Intravesical cretostimogene will be instilled in combination with 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 36:
Re-induction is permitted at month 3 if persistent high-grade Ta or CIS is noted at biopsy. Response assessment include cystoscopy with directed biopsy (as indicated) every 3 months for the first 2 years and every 6 months starting in year 3, as well as serial urine cytology and CT/MR urogram. The primary endpoint for the CIS population is complete response at any time and high-grade event free survival for patients with papillary-only disease. Secondary endpoints include duration of response, all cause event free survival, bladder cancer specific survival, progression free survival, cystectomy-free survival, safety, and tolerability. Exploratory outcome measures consist of health related quality of life, overall survival, and biomarker assessments. Key trial features include a broad and inclusive population, mandatory biopsy at week 51, and central pathology review.
Cohort B is now open for enrollment in collaboration with the Society of Urologic Oncology Clinical Trials Consortium (SUO-CTC) in both the United States and Canada.
Presented by: Trinity J. Bivalacqua, MD, PhD, Penn Medicine, Philadelphia, PA
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 Society of Urologic Oncology (SUO) annual meeting held in Phoenix, AZ, between the 2nd and 5th of December 2025.
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CORE-008 Cohort B Investigates Cretostimogene Grenadenorepvec for BCG-Exposed High-Risk NMIBC - Trinity Bivalacqua