On the morning of February 14, 2025 (UTC-8), Professor Xinan Sheng from Peking University Cancer Hospital presented the latest efficacy and safety data from the phase II clinical trial (NCT05297552, Study ID: RC48-C017) on Disitamab Vedotin (DV) as the neoadjuvant therapy combined with perioperative Toripalimab for the treatment of HER2-expressing muscle-invasive bladder cancer (MIBC) at the ongoing 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) held in San Francisco, USA. This marks the first public disclosure of results from a prospective clinical study investigating an ADC drug combined with immunotherapy as a perioperative therapy for MIBC. ASCO GU is one of the top urologic oncology conferences that leading experts worldwide in this field attend.

 The NCT05297552 study explored the synergy between the targeted therapy and immunotherapy in the perioperative setting for MIBC. Specifically, it assessed the safety and efficacy of the novel combination therapy featuring the neoadjuvant DV, a HER2-targeting ADC drug initially developed by RemeGen Co., Ltd. (RemeGen), and perioperative Toripalimab, a PD-1 inhibitor. In May 2024, based on the NCT05297552 study, the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) granted breakthrough therapy designation to DV. The preliminary results of this study were presented at the 2024 ASCO Annual Meeting, arousing intense interest and discussion among experts worldwide. The recently updated data indicated clinically meaningful benefits of this therapeutic approach.

 In the NCT05297552 study, 47 eligible patients (10.6% with HER2 IHC 1+, 57.4% with IHC 2+, and 31.9% with IHC 3+) received the investigational neoadjuvant therapy, among whom 33 patients underwent radical cystectomy and pelvic lymph node dissection (RC + PLND). As of the data cut-off date on December 3, 2024, the study demonstrated promising efficacy and manageable safety profiles:

   Ø  The pathological complete response (pCR) rate reached an impressive 63.6% (95% CI: 45.1% - 79.6%), nearly doubling that observed with the traditional neoadjuvant chemotherapy (36%-42%). The pathological response rate was 75.8% (95% CI: 57.7% - 88.9%) and the pCR rate among HER2 IHC 3+ patients stood at 84.6%. These findings suggested potential benefits for patients with HER2-overexpressing (IHC 3+/2+) or HER2-low (IHC 1+) MIBC. A high pCR rate positively correlates with improved postoperative recurrence-free survival.

    Ø  The 12-month event-free survival (EFS) rate was 92.5% (95% CI: 72.8% - 98.1%) in all evaluable participants and 88.1% (95% CI: 70.7% - 95.4%) in the intent-to-treat population.

    Ø  The therapy exhibited a manageable safety profile. The incidence of grade 3 or higher treatment-emergent adverse events (TEAEs) was only 27.7%, notably lower than the traditional chemotherapy regimen (40%-50%), suggesting a favorable tolerability.

 RemeGen is advancing research on targeted and personalized therapies for bladder cancer through indication expansion and therapy innovation of DV, aiming to provide more potent treatment options for patients worldwide and fulfill its commitment to benefiting global patients with Chinese wisdom. Currently, studies are proceeding to explore the feasibility of expanding DV-based regimens from later-line to front-line therapies for locally advanced or metastatic urothelial cancer. There are also plans to broaden the research of DV as a neoadjuvant therapy for MIBC to the entire perioperative period and investigate the synergy between DV and chemotherapy or other immunotherapies in treating urothelial cancer.