Bulumtatug fuvedotin (BFv; 9MW2821) plus toripalimab in perioperative patients with muscle-invasive bladder cancer (MIBC): Results of cohort A from a phase 2 study.

4609 Background: Radical cystectomy with pelvic lymph node dissection (RC+PLND) has always been the standard treatment for MIBC. Perioperative treatment, especially cisplatin-based neoadjuvant therapy, could reduce the risk of tumor recurrence effectively and prolong the survival of patients. BFv, a novel Nectin-4 antibody-drug conjugate, combined with toripalimab, has demonstrated promising efficacy and safety profile in advanced urothelial cancer patients. This provides possibilities for the perioperative treatment of MIBC. Here we report the preliminary results of BFv plus toripalimab in patients with perioperative MIBC (cohort A). Methods: Patients with MIBC (cT2-4aN0-1M0) can be enrolled in cohort A. Eligible patients will receive BFv plus toripalimab for 4 cycles in neoadjuvant stage, and then proceed with RC+PLND. After surgery, patients will receive BFv plus toripalimab for 6 cycles and toripalimab only for the next 11 cycles in the adjuvant stage. The primary endpoint was pathological complete response (pCR). Main secondary endpoints were pathological downstaging (PDS) rate and disease-free survival (DFS), overall survival (OS) and safety. Results: As of 4 Jan 2026, 32 patients were enrolled in the cohort A. 7 patients had completed neoadjuvant therapy and 6 of them were performed with RC+PLND. One patient achieved CR in the neoadjuvant stage and refused to undergo the surgery. pCR rate was 66.7% (4/6, 95%CI 22.3-95.7), PDS rate was 83.3% (5/6, 95%CI 35.9-99.6). DFS and OS were not mature. Safety profile was consist with previous study. No new safety signals of BFv or toripalimab were observed in this study. Conclusions: This study showed remarkable preliminary efficacy of BFv plus toripalimab in perioperative patients with MIBC. It may offer a new choice for MIBC patients and deserve to be further investigation. Clinical trial information: NCT07314723 .