Cretostimogene 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. Efficacy and safety of cretostimogene monotherapy and in combination with pembrolizumab for HR BCG-UR NMIBC and nivolumab for MIBC have been previously published. CORE-008 (NCT06567743) is a Phase 2, multi-arm, multi-cohort trial evaluating the efficacy and safety of intravesical cretostimogene monotherapy and in rational combinations in patients with HR NMIBC; Cohort CX evaluates cretostimogene in combination with intravesical gemcitabine in patients with BCG-exposed or BCG-UR NMIBC. The combination is hypothesized to leverage complementary mechanisms and immune-modulating synergy, with the advantage of an intravesical-only approach that mitigates systemic toxicity.
Patients are randomized to receive intravesical cretostimogene and gemcitabine concurrently vs sequentially in a classic induction and maintenance schedule through Month 36. Re-induction is permitted at Month 3 if persistent HG Ta or CIS is confirmed by histopathology. Response assessments include serial cystoscopy, urine cytology, axial imaging and biopsies (as indicated). Co-primary endpoints include HG-EFS and Safety.
As of 06 October 2025, enrollment of 54 patients is complete, including 61.1% BCG-exposed and 38.9% BCG-UR. 81.5% are 65 years of age or older, 22.2% are female, and 13.0% are ECOG PS 1/2. At baseline, 50.9% have CIS-containing and 49.1% with HG papillary-only NMIBC. Median cretostimogene exposure is 5.14 weeks (range 0.14-20.29) with median follow up duration of 68.5 days (IQR 36-92). The HG-EFS at 3 months in evaluable patients is 94.1% (16/17) (95% CI 82.9-100%). 5.9% (1/17) were re-induced. There are no progression events to MIBC or metastatic disease. The most common adverse events are low-grade and localized to the bladder. There are no treatment-related grade 3+ adverse events and no treatment-related serious adverse events. 1.9% (1/54) had a treatment-related discontinuation owing to Grade 1 adverse events and 1.9% (1/54) had a dose delay due to a related adverse event resulting in two missed doses. Further data, including based on treatment schedule, will be presented.
Cretostimogene with intravesical gemcitabine demonstrates promising efficacy and a favorable safety profile in patients with HR BCG-exposed or BCG-UR NMIBC. Further investigation of this combination regimen is warranted and highlights the potential benefit of complementary intravesical MOAs.
CG Oncology