(UroToday.com) The 2026 GU ASCO annual meeting featured a urothelial carcinoma session and a presentation by Dr. Gary Steinberg discussing the first results from CORE-008 cohort A, a phase 2 study of intravesical cretostimogene grenadenorepvec in patients with high-risk BCG-naïve non-muscle invasive bladder cancer.
Standard of care treatment for high-risk non-muscle invasive bladder cancer includes TURBT followed by intravesical BCG. However, high recurrence rates and BCG shortages highlight the need for effective, well-tolerated, and readily available treatment options. Cretostimogene grenadenorepvec is an oncolytic immunotherapy with dual mechanisms of action. It replicates in and lyses cancer cells with Rb-E2F pathway alterations, while simultaneously amplifying anti-tumor immune response, further mediated by the GM-CSF transgene. CORE-008 is a phase 2, multi-arm, multi-cohort trial evaluating the efficacy and safety of intravesical cretostimogene in patients with high-risk non-muscle invasive bladder cancer.
Cohort A includes patients aged≥18 years, ECOG performance status of 0-2, with pathologically confirmed high-risk non-muscle invasive bladder cancer with CIS, and who are BCG-naïve (no prior BCG, BCG administered > 24 months ago, or receipt of only 1-2 BCG doses within the past 24 months). Patients receive intravesical cretostimogene 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 HG Ta and/or CIS is noted at biopsy. Response assessments included urine cytology, serial cystoscopy with directed biopsy, and axial imaging (as indicated). The primary endpoint is complete response at any time. Enrollment is complete.
As of September 1, 2025, data cut off (median follow-up 4.6 months), 54 patients in Cohort A received treatment with intravesical cretostimogene. Overall, 88.8% of participants were 65 years of age or older, 9.3% are female, and 18.5% have an ECOG performance status of 1. Baseline disease characteristics demonstrate CIS alone in 44.4%, CIS + HG Ta in 31.5%, and CIS + T1 in 24.1%:
There were 53 (98.1%) patients who completed induction, with 49 assessed for efficacy. The median exposure of the cohort is 15.3 weeks (range 1.1, 41.0 weeks). The complete response rate at any time in evaluable patients is 83.7% (41/49) (95% CI 70.3-92.7%):
Regarding subgroup analyses, there were consistent treatment effects:
No patients progressed to muscle-invasive bladder cancer or metastatic disease. The safety and tolerability profile of cretostimogene is consistent with prior clinical trials with this agent. The most common adverse events are low-grade and localized to the bladder. There are no related serious adverse events, grade 3+ adverse events or treatment-related discontinuations. There were 98.1% of patients (53/54) who completed all protocol-defined treatments, including 96.3% for the original administration and 100% for the optimized administration.
Dr. Steinberg concluded his presentation discussing the first results from CORE-008 cohort A with the following take-home points:
- Cretostimogene has promising clinical efficacy and safety in patients with high-risk, BCG-naïve non-muscle invasive bladder cancer disease
- These findings support the further development of cretostimogene in other early, high-risk non-muscle invasive bladder cancer disease states
- Currently, additional treatment arms are planned for patients with BCG-naïve non-muscle invasive bladder cancer disease
Presented by: Gary D. Steinberg, MD, NYU Langone Health, New York, NY