Disitamab Vedotin Plus Toripalimab for Bladder Preservation in HER2-Positive Muscle-Invasive Bladder Cancer: A Phase II, Open-Label, Randomized Clinical Trial

Eligible pts are aged 18 years with predominant urothelial carcinoma, who were HER2-expressing (IHC1+/2+/3+) and unsuitable for platinum-based chemotherapy; not received systematic treatment in the past and ECOG PS of 0-1. A total of 60 patients are planned to be enrolled. All subjects will undergo initial diagnostic transurethral resection of bladder tumor (TURBT) followed by pharmacotherapy initiation within two weeks postoperatively. In Stage 1, patients will receive four cycles of RC48-ADC (2mg/kg, iv, D1, Q2W) combined with toripalimab (3mg/kg, iv, Q2W). Patients achieving clinical complete response (cCR) will undergo Re-cTURBT with multi-site bladder biopsies to confirm local pathological complete response (pCR). Patients who fail to achieve cCR will undergo radical cystectomy (RC). It should be noted that local pCR here refers to the pathological assessment of residual tumors through Re-cTURBT and multipoint biopsies in patients who achieved complete clinical response (cCR) and requested bladder preservation. Patients attaining local pCR will proceed to the Stage 2 and be randomized into two cohorts: Cohort 1 will receive RC48-ADC (2mg/kg, iv, D1, Q3W) plus toripalimab (3mg/kg, iv, Q3W) for 6 cycles, while Cohort 2 will undergo the same regimen for 6 cycles followed with RC48 (2mg/kg, iv, D1, Q4W) combined with toripalimab (2mg/kg, iv, D1, Q4W) for 6 additional cycles. The primary end point is one year BI-DFS. The secondary end points included overall survival (OS), recurrence-free survival (RFS), clinical complete responsec (cCR) and safety.