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Oncolytic Adenoviral Therapy in Combination with Nivolumab in Muscle-Invasive Bladder Cancer - Expert Commentary

Neoadjuvant chemo-immuno therapy followed by radical cystectomy is the standard of care for patients with muscle-invasive bladder cancer (MIBC). However, up to 40% of patients are ineligible to receive Cisplatin-based chemotherapy. In a single-arm phase 1b trial, Li et al. investigated the safety and efficacy of combining cretostimogene (CG0070, an oncolytic adenovirus encoding GM-CSF) with nivolumab in cisplatin-ineligible patients with MIBC.

Twenty-one cisplatin-ineligible patients received 6 weekly intravesical cretostimogene instillations plus nivolumab (480mg IV) at weeks 2 and 6. No dose-limiting toxicities occurred. The most common treatment-related adverse events were grade 1/2 catheter leakage (24%), bladder spasms (14%), and fatigue (19%). The pathologic complete response rate was 42.1% (8/19 evaluable patients). One-year recurrence-free survival was 70.4% (95% CI: 53.0-93.4%). Response correlated with baseline tumor mutational burden and E2F target gene expression but not PD-L1 status. Correlative studies showed increased tumor-infiltrating T-cells and formation of tertiary lymphoid structures in responders, with evidence of coordinated cellular and humoral anti-tumor immunity. CD138+ isotype-switched plasma cells accumulated within tertiary lymphoid structures post-treatment.

This important study highlights the promise of this approach and supports further investigation of this combination in cisplatin-ineligible MIBC patients.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine

References:

  1. Li R, Villa NY, Yu X, et al. Oncolytic immunotherapy with nivolumab in muscle-invasive bladder cancer: a phase 1b trial. Nat Med. 2024. doi:10.1038/s41591-024-03324-9.
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