Multicenter phase 2 study of neoadjuvant ddMVAC plus durvalumab with or without tremelimumab in muscle-invasive bladder carcinoma

The multicenter phase 2 NEMIO study in France evaluated efficacy and safety of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicine and cisplatin (ddMVAC) plus durvalumab with or without tremelimumab in patients with muscle-invasive bladder cancer (MIBC; cT2-T4a N0-1). Patients received ddMVAC once every two weeks x 4 cycles plus durvalumab with tremelimumab (n=59) or durvalumab alone (n=60) once every 4 weeks x two doses (C1D1 and C3D1) followed by radical cystectomy (RC). Coprimary endpoints (local assessment) were pathologic complete response (pCR) rate and grade ≥ 3 treatment-related adverse events. The study would be considered positive if the pCR rate was ≥ 45% and the rate of grade ≥ 3 TRAEs was ≤ 30%. Among 119 randomized patients, 113 underwent RC. The overall Bayesian posterior mean pCR rate was 48.7% (95% CI 35.9-61.6) in the group with durvalumab alone and 46.3% (33.9-58.9) in the group with durvalumab plus tremelimumab; Bayesian posterior mean grade ≥ 3 TRAEs occurred in 30.4% and 49.6%, whereas two-year event-free survival rates were 75% and 77% and two-year overall survival rates were 85% and 88%, respectively. The authors conclude that neoadjuvant ddMVAC plus durvalumab demonstrated encouraging pCR rate, favorable early survival outcomes, and manageable safety among MIBC patients. Adding tremelimumab provided similar pCR but worse toxicity.