Single-center phase 1b trial of neoadjuvant oncolytic immunotherapy plus nivolumab for muscle-invasive bladder cancer

Cretostimogene grenadenorepvec (CG) is a recombinant type-5 oncolytic adenovirus designed to selectively replicate in bladder cancer cells with alterations in the retinoblastoma pathway. A phase 1b trial at Moffitt Cancer Center (Tampa, FL) evaluated neoadjuvant intravesical CG plus systemic nivolumab in cisplatin-ineligible patients with cT2-4aN0-1M0 muscle-invasive bladder cancer. No dose-limiting toxicity was observed. The pathologic complete response rate was 42.1%, and the 1-year recurrence-free survival rate was 70.4%. Pathologic response was associated with baseline free E2F activity and tumor mutational burden but not PD-L1 status. The authors conclude that these results highlight the potential of this combination regimen to enhance therapeutic efficacy in cisplatin-ineligible patients with muscle-invasive bladder cancer.