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Efficacy and Safety of Intravesical Cretostimogene Grenadenorepvec Plus Gemcitabine in High-Risk BCG-Exposed Or BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer (CORE-008 Cohort CX)
Boris Gershman, MD1, Aaron Berger, MD2, Mark D. Tyson, MD, MPH3, Christopher M. Pieczonka, MD4, Kyle Rose, MD5, Gary D. Steinberg, MD6, Siamak Daneshmand, MD7, Colin P.N. Dinney, MD8, Trinity Bivalacqua, MD9.
1Beth Israel Deaconess Medical Center,, Boston, MA, USA, 2Associated Urological Specialists, Chicago Ridge, IL, USA, 3Mayo Clinic, Phoenix, AZ, USA, 4Associated Medical Professionals of New York (an affiliate of US Urology Partners), Syracuse, NY, USA, 5Oschner Medical Center, New Orleans, LA, USA, 6Rush University Medical Center, Chicago, IL, USA, 7University of Southern California/Norris Comprehensive Cancer Center, Los Angele, CA, USA, 8University of Rochester, Rochester, NY, USA, 9University of Pennsylvania, Philadelphia, PA, USA.
Background: Cretostimogene has demonstrated activity as monotherapy and in combination with checkpoint inhibitors in BCG-unresponsive NMIBC and muscle-invasive bladder cancer. CORE-008 (NCT06567743) is a phase 2, multi-arm, multi-cohort trial evaluating intravesical cretostimogene as monotherapy and in combinations in patients with high-risk NMIBC. Cohort CX evaluates cretostimogene combined with intravesical gemcitabine in patients with BCG-exposed or BCG-unresponsive disease, aiming to leverage complementary mechanisms of action within an intravesical-only treatment approach
. Methods: Patients were randomized to receive intravesical cretostimogene and gemcitabine concurrently vs sequentially including induction for six weeks and maintenance schedules through Month 24, with optional treatment extending to Month 36. Sequential treatment followed a repeating cycle of cretostimogene for two weeks, then gemcitabine the following week. Patients were eligible for re-induction for biopsy-proven HG Ta or CIS at Month 3. Response assessments included serial cystoscopy, urine cytology, imaging and biopsies (as indicated). Co-primary endpoints include High Grade Event-Free Survival (HG-EFS) and safety.
Results: As of November 28, 2025, enrollment was completed with 55 patients with a median follow-up of 106 days (IQR 99-134). Among the 54 patients who received at least one dose of cretostimogene, 61.1% were BCG-exposed and 38.9% BCG-UR. Baseline characteristics included 81.5% aged ≥65 years, 22.2% female, and 13.0% with ECOG performance status 0-2. Disease characteristics included 51.9% with CIS-containing disease and 48.1% with HG Ta/T1 NMIBC. Forty-two patients completed 3-month efficacy assessments. Three-month HG-EFS was 88.1% (37/42; 95% CI 74.4-96.0). No progression to muscle-invasive or metastatic disease was observed. Treatment-related adverse events were low grade and localized to the bladder, with no serious events reported.
Conclusions: Cretostimogene with intravesical gemcitabine demonstrates promising early efficacy and a favorable safety profile. Further investigation of this combination regimen is warranted and highlights the potential benefit of complementary intravesical mechanisms of action.
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