Efficacy and safety of disitamab vedotin combined with toripalimab as neoadjuvant treatment for patients with locally advanced muscle-invasive bladder cancer: A mono-institutional retrospective study.

726 Background: Currently, the efficacy of cisplatin-based neoadjuvant chemotherapy for patients with muscle-invasive bladder cancer (MIBC) is unsatisfied. Disitamab vedotin (RC48) as an antibody-drug conjugate is composed by a monoclonal antibody against human epidermal growth factor receptor 2 (HER2) and a cytotoxic agent monomethyl auristatin E. Although this drug was approved in 2021 for HER2-overexpressing gastric cancer, disitamab vedotin as mono- or combination regimen is in clinical development for treating other solid tumors now. This study aims to assess the safety and efficacy of disitamab vedotin combined with toripalimab as neoadjuvant treatment for patients with HER2 positive locally advanced MIBC. Methods: The data of patients with HER2 positive locally advanced MIBC who received combination therapy [disitamab vedotin (2.0mg/kg, iv, D 1 , Q3W) combined with toripalimab (240mg, iv, D 1 , Q3W) were collected retrospectively and analyzed. The primary endpoint was pathological complete response (pCR), and the secondary endpoints included objective response rate (ORR), overall survival (OS) and treatment-related adverse events (TRAEs). All outcomes were assessed by a blinded independent review committee. Results: The data of 20 included patients who received combination regimen from 2023 Jun to 2023 Sept were analyzed. Among them, the median age was 65 (47-86) years. The overall pCR was 79%, while the ORR was100%. The median PFS was 4.5 (2.45-9.6) months, and overall survival (OS) was not reached. The most common TRAEs were nausea (7,35.0%), alopecia (8,40.0%), and rash (3,15%). Only 1 patients reported Grade 3 TRAE (feeble), and no grade 4 TRAEs were observed. Conclusions: The safety and efficacy of neoadjuvant disitamab vedotin combined with toripalimab in patients with HER2 positive locally advanced MIBC were promising. This study will be verified in future.