On the morning of February 14, 2025 (UTC-8), at the ongoing 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) held in San Francisco, USA, Professor Xinan Sheng from Peking University Cancer Hospital delivered the latest efficacy and safety data from the phase II clinical trial (NCT05297552, Study ID: RC48-C017) of Disitamab Vedotin (DV) in combination Toripalimab as the neoadjuvant therapy for HER2-expressing muscle-invasive bladder cancer (MIBC) in an oral presentation. This marks the first public disclosure of results from a prospective clinical study investigating an ADC drug in combination with an immunotherapy as a perioperative therapy for MIBC. The pathological complete response (pCR) rate reached an impressive 63.6%, which is a breakthrough improvement compared with traditional neoadjuvant chemotherapies (36%-42%). 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 DV, a HER2-targeting ADC drug initially developed by RemeGen Co., Ltd. (RemeGen), and 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 and led to widespread attention and discussion among experts worldwide. The updated data at ASCO GU further validated the clinical 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:

● The pathological complete response (pCR) rate reached an impressive 63.6% (95% CI: 45.1% - 79.6%), nearly doubling that observed with traditional neoadjuvant chemotherapies (36%-42%). The pathological response rate was 75.8% (95% CI: 57.7% - 88.9%). The study showed that for patients with baseline clinical stage of T2N0, the postoperative pCR rate reached 85.7%. A pCR rate of 55.6% was also achieved in patients with other pathological subtypes of urothelial carcinoma at baseline. Patients benefited significantly regardless of PD-L1 positive/negative and regardless of HER2 expression status (IHC 1+/2+/3+), among whom the pCR rate stood at 84.6% for HER2 IHC 3+ patients.

● The 12-month event-free survival (EFS) rate of all patients who underwent radical cystectomy was 92.5%, and the 18-month EFS rate was 85.9%.

● 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. Currently, studies are in-progress to explore the feasibility of expanding DV-based regimens from later-line to front-line treatment 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.