A prospective, multicenter, single-arm, phase II, exploratory clinical trial protocol for the evaluation of efficacy and safety of Distitamab Vedotin plus tislelizumab combined with re-TURBT for the treatment of high-HER2-expressing (2+/3+) non-muscle invasive bladder cancer at high/very high-risk

Introduction: Patients with HER2-overexpressing non-muscle-invasive bladder cancer are (NMIBC) at high risk of relapse after BCG treatment. Disitamab Vedotin combined with Tislelizumab shows promising prospects for the treatment of HER2-positive, high/very high-risk NMIBC. Methods and analysis: This is the proposed protocol of a prospective, multicenter, single-arm clinical trial that will enroll 40 patients. Eligible patients will receive an initial maximum TURBT, followed by 3–4 cycles of Distitamab Vedotin plus Tislelizumab after the initial maximum TURBT. This process was repeated every 3 weeks. Thereafter, patients are scheduled to complete a re-TURBT within 6 weeks and then put on a 2‒4 cycles of Distitamab Vedotin plus Tislelizumab postoperatively. The primary endpoint is 1-year event-free survival (target: 92%). Secondary endpoints include 3-year EFS, 2-year bladder intact disease-free survival, time to radical cystectomy, recurrence-free survival, overall survival, quality of life (QLQ-C30), and adverse events. Discussion: This study is designed to evaluate the efficacy and safety of this novel combination therapy with re-TURBT for HER2 2-3+ high/very high-risk NMIBC.