Intravesical Administration of Durvalumab for High-risk Non-muscle-invasive Bladder Cancer: A Phase 2 Study by the Hellenic GU Cancer Group.

For patients with high-risk non-muscle-invasive bladder cancer (NMIBC) for whom bacillus Calmette-Guérin (BCG) treatment has failed, bladder preservation is a high priority. Immune checkpoint inhibitors have shown promise, but systemic administration is associated with substantial toxicity. In this single-arm phase 2 study, 30 patients with NMIBC after BCG failure were treated with intravesical durvalumab every 6 wk. The maximum tolerated dose in the run-in phase was 1000 mg. In phase 2, the high-grade relapse (HGR)-free rate at 1 yr after completing therapy was 39% (95% confidence interval [CI] 18-59%). HGR-free rates at 1, 3, and 6 mo after completing study treatment were 70% (95% CI 45-85%), 55% (95% CI 31-74%), and 39% (95% CI 18-59%), respectively. At 13 mo after completing enrolment, four patients in phase 2 had experienced progression to stage ≥T2; the 1-yr bladder-intact survival rate was 78% (95% CI 57-89%). The only treatment-related adverse event was grade 1 haematuria in five patients (17%). In conclusion, intravesical durvalumab 1000 mg every 6 wk is feasible after BCG failure in patients with high-risk NMIBC, with negligible toxicity and encouraging efficacy. Intravesical durvalumab may be more attractive than systemic administration of immune checkpoint inhibitors and warrants further investigation as a treatment for NMIBC. This trial is registered on ClinicalTrials.gov as NCT03759496.