Durvalumab (PD-L1) + ddMVAC Hits ~49% pCR in Neoadjuvant MIBC; Tremelimumab (CTLA-4) Adds Toxicity

NEMIO (Phase I/II, randomized, noncomparative; NCT03549715) tested ddMVAC plus durvalumab with or without tremelimumab ahead of radical cystectomy in cisplatin-eligible cT2–T4a N0–1 muscle-invasive bladder cancer (119 treated; 113 cystectomy). Bayesian posterior mean pCR (ypT0N0) was 48.70% with ddMVAC+durvalumab (95% CI 35.93–61.56) and 46.27% with ddMVAC+durvalumab+tremelimumab (95% CI 33.92–58.85); in exploratory PD-L1-high tumors, pCR was 68.25% vs 33.49% in PD-L1-low/negative (PD-L1 data n=103). Grade ≥3 TRAEs were 30.48% in the doublet vs 49.63% in the triplet (overall 40.95%); immune-related AEs occurred in 26.9% (grade ≥3 4.2%), and 2-year EFS/OS were 75%/85% (doublet) and 77%/88% (triplet)—directionally above historical neoadjuvant cisplatin chemo benchmarks where pCR is often in the ~25–40% range depending on regimen and series, but the triplet misses the trial’s ≤30% grade ≥3 TRAE bar.