(UroToday.com) The 2025 South Central AUA annual meeting included a session on bladder cancer, featuring a trials in progress presentation from Colin Dinney, MD, discussing updates to the CORE-008 trial. Treatment for patients with high-risk non-muscle invasive bladder cancer consists of TURBT followed by intravesical BCG, yet high recurrence rates and the ongoing BCG shortage highlight the need for effective, well-tolerated, and readily available treatment options.
Cretostimogene grenadenorepvec is an oncolytic immunotherapy with a dual mechanism of action. It selectively replicates in and lyses bladder cancer cells with Rb-E2F pathway alterations. The subsequent release of virus- and tumor-specific antigens initiates antitumor immune activation, which is further amplified by the transgene for GM-CSF, a potent cytokine. Cretostimogene received both Fast Track and Breakthrough Therapy Designations by the US FDA for the high-risk BCG-Unresponsive non-muscle invasive bladder cancer with CIS indication. Given the strength of these data, the CORE-008 clinical trial (NCT06567743) was developed as a phase 2, multi-arm, multi-cohort trial to further evaluate the efficacy and safety of cretostimogene in patients with high-risk non-muscle invasive bladder cancer.
Eligibility criteria include pathologic confirmation of high-risk non-muscle invasive bladder cancer, both CIS-containing and papillary only, as defined by the AUA guideline. Cohort A (BCG-naive) includes patients who have not received prior BCG, and Cohort B (BCG-exposed) consists of patients who have received prior BCG and recurred at the initial clinical evaluation or at a delayed time point. Cohort CX, recently added to the study, will evaluate safety and high-grade event-free survival of cretostimogene in combination with intravesical gemcitabine, either concurrent (Arm 1) or sequential (Arm 2) in BCG-exposed and BCG-unresponsive patients. It is postulated that the combination will utilize complementary mechanisms of action and potential immune-modulating synergy to enhance outcomes. Intravesical cretostimogene will be instilled 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 36. Re-induction is permitted:
The primary endpoint for the CIS population is complete response at any time, and high-grade event-free survival is the primary endpoint for patients with papillary-only disease:
Secondary endpoints will include duration of response, all-cause event-free survival, bladder cancer-specific survival, cystectomy-free survival, safety, and tolerability. Exploratory outcome measures include health-related quality of life, overall survival, and biomarker assessments. Cohort A's first results will be reported imminently, Cohort B has received collaborative support from the Society of Urologic Oncology-Clinical Trials Consortium (SUO-CTC), and Cohort CX has completed enrollment.
Presented by: Colin Dinney, MD, MD Anderson Cancer Center, Houston, TX
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 South Central American Urological Association (AUA) Annual Meeting, Orlando, FL, Wed, Sept 10 – Sat, Sept 13, 2025.