Editor’s Note: Approximately 5% of urothelial carcinoma (UC) patients present with distant metastasis at diagnosis, and 30% of early-stage patients relapse or develop metastasis despite active treatment. With the emergence of antibody-drug conjugates (ADCs), the median survival of advanced UC patients has extended to 31.5 months. However, the overall survival remains suboptimal. To address this challenge, Professor Dingwei Ye and his team at Fudan University Cancer Hospital initiated a phase II clinical trial of BL-B01D1 for locally advanced or metastatic UC in 2023. The study was presented orally at the 2024 European Society for Medical Oncology (ESMO) Congress, and recently published in the Journal of Clinical Oncology (JCO, IF 41.6). 
BL-B01D1 (izalontamab brengitecan) is the world’s first bispecific ADC targeting EGFR and HER3. It binds to these receptors on tumor cells, internalizes via endocytosis, and releases the payload Ed-04, which disrupts DNA replication and RNA synthesis, leading to tumor cell death.This multi-center study enrolled 41 patients nationwide: 34 received 2.2 mg/kg, 4 received 2.5 mg/kg, and 3 received 2.75 mg/kg. In the 2.2 mg/kg cohort, the confirmed objective response rate (ORR) was 44.1%, and the disease control rate (DCR) was 88.2%. Among 15 patients who had received only one prior line of therapy (chemotherapy or ADC), the ORR reached 80.0%. After a median follow-up of 10.2 months, the median progression-free survival (PFS) was 7.3 months (95% CI, 5.5–9.8), and the median duration of response (DoR) was 11.3 months (95% CI, 4.3–NR).This pioneering study demonstrated the clinical efficacy of an EGFR–HER3 bispecific ADC in advanced UC, filling a critical treatment gap for Chinese patients and opening a new chapter in post-line UC management. A phase III clinical trial of BL-B01D1 for locally advanced or metastatic UC is currently underway.As one of China’s earliest centers to establish a multidisciplinary approach for bladder cancer, the hospital’s urology department collaborates with departments of medical oncology, radiotherapy, pathology, imaging, and nuclear medicine to provide comprehensive, patient-centered care.The Urology Department of Fudan University Cancer Hospital is among the first in China to conduct clinical studies in genitourinary oncology and has passed inspections by both the NMPA and FDA. According to NMPA’s Center for Drug Evaluation (CDE), Professor Ye has led 146 clinical studies, including more than 40 focused on urothelial carcinoma, ranking first nationwide. The team’s ongoing projects span the entire disease spectrum—from early to perioperative, advanced, and end-stage bladder cancer—covering next-generation ADCs, targeted drugs, viral vectors, and immunotherapies, surpassing even many leading international cancer centers. This enables Chinese patients to access the world’s most advanced treatments.The department also prioritizes early detection. The team has developed several biomarker diagnostic kits for early tumor identification and recurrence monitoring. For postoperative patients, cystoscopic examinations are conducted using pain-free flexible cystoscopy, significantly reducing discomfort. Advanced imaging technologies, such as narrow-band imaging (NBI), fluorescence, and confocal microscopy, enable early detection and prompt treatment of recurrence, improving cure rates substantially Reports show that the five-year overall survival rate for bladder cancer patients treated at Fudan University Cancer Hospital has reached 74%. Survival outcomes have not only caught up with but now surpass Western benchmarks. This achievement is attributed to the team’s fourfold strategy: early diagnosis, precise surgery, comprehensive multidisciplinary care, and internationally oriented translational research.Given the high recurrence and invasion potential of bladder tumors, the surgical team emphasizes standardized, tumor-free techniques to maximize both survival and quality of life. In 2024, the department performed over 2,400 bladder cancer surgeries, maintaining its leading national ranking for consecutive years. The team continues to innovate, adopting cutting-edge techniques such as 3D laparoscopy, fluorescence laparoscopy, and new-generation robotic systems. For patients undergoing cystectomy, the “orthotopic neobladder” reconstruction technique allows them to live with dignity without permanent urine bags, greatly enhancing postoperative quality of life.For patients unsuitable for or unwilling to undergo cystectomy, the multidisciplinary team designs individualized bladder-preserving strategies based on the latest evidence and technologies. Professor Dingwei Ye has also led the development of China’s first multidisciplinary consensus on bladder-preserving treatment for bladder cancer, involving over 40 institutions nationwide. Results show that bladder-preserving outcomes at Fudan University Cancer Hospital are comparable to cystectomy in efficacy but superior in quality of life.The rehabilitation team participates throughout pre-, intra-, and postoperative care to ensure optimal recovery and sustained quality of life.
Professor Dingwei Ye
Professor Xiaojie Bian
