A multi-center phase Ib/II study of RC48-ADC combined with tislelizumab as neoadjuvant treatment in patients with HER2 positive locally advanced muscle-invasive urothelial bladder cancer (Hope-03).

作者：Feng Wen, Tianhai Lin, Ping Tan, Jing Deng, Min Ren, Mengni Zhang, Xiaonan Zheng, Peng Zhang, Yali Shen · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.5_suppl.795 · 被引用次数：3 · 研究领域：Bladder and Urothelial Cancer Treatments、Cancer Immunotherapy and Biomarkers、Peptidase Inhibition and Analysis

795 Background: To evaluate the safety and efficacy of RC48-ADC, a humanized anti-HER2 antibody conjugated with monomethyl auristatin E, and tislelizumab, a PD-1 antibody, as a novel neoadjuvant treatment combination in patients with HER2 positive locally advanced muscle-invasive bladder cancer (MIBC). The study design has been presented at 2022 ESMO Asia meeting, and preliminary results will be reported this time. Methods: This is a Ib/II, multi-center, open-label, single-arm study (ChiECRCT20210564). Patients with pathological and imaging diagnosed cT2-4bN0-3M0-1a HER2 positive (Immunohistochemistry status 3+ or 2+ or 1+) MIBC. Of them, 6 patients are enrolled in the dose-escalation phase, and 45 patients enter into phase II study. RC48-ADC is given every 2 weeks with a maximum dose of 120mg intravenously, and tislelizumab is given every three weeks at the dose of 200mg intravenously. Patients without disease progression will receive radical cystectomy or bladder-sparing therapies based on individual risk profiles and preferences. The primary endpoints are clinical complete remission rate (cCR, T0/Ta/Tis), pathological complete remission rate (pCR) and safety. Results: Inclusion has been closed, with a total of 51 patients successfully enrolled, consisting of 7 females and 44 males. The median age was 70 ± 10.16 years. Among the participants, 3 patients were HER2(1+), 26 patients were HER2(2+), and 22 patients were HER2(3+). The median follow-up duration was 12.8 ± 1.81 mon...