Multicenter phase 2 trial of oncolytic adenoviral therapy plus pembrolizumab for BCG-unresponsive non-muscle-invasive bladder cancer

Cretostimogene grenadenorepvec is a serotype-5 oncolytic adenovirus designed to selectively replicate in cancer cells with retinoblastoma pathway alterations. The multicenter phase 2 CORE-001 trial evaluated the combination of intravesical cretostimogene with systemic pembrolizumab in patients with BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). Complete response (CR) rate in the intention-to-treat population at 3 months was 82.9% (95% CI 70,4-95.3), while CR rate at 12 months was 57.1% (40.7-73.5), meeting the primary endpoint, and CR at 24 months was 51.4% (34.9-68.0). No patient progressed to muscle-invasive bladder cancer. Adverse events attributed to cretostimogene were low-grade, self-limiting, and predominantly limited to bladder-related symptoms. A total of 14.3% of patients developed grade 3 treatment-related adverse events, all related to pembrolizumab. The authors conclude that combination of intravesical cretostimogene and systemic pembrolizumab demonstrated enduring efficacy among patients with BCG-unresponsive CIS.