9MW2821, a novel Nectin-4 antibody-drug conjugate (ADC), combined with toripalimab in treatment-naïve patients with locally advanced or metastatic urothelial carcinoma (la/mUC): Results from a phase 1b/2 study.

作者：Shusuan Jiang, Hongqian Guo, Hongchen Qu, Yuchen Bai, Benkang Shi, Peng Zhang, Xin Yao, Tie Yang, Hang Huang, Manming Cao, Jun Guo, Xinan Sheng, Jingming Dong, Pei Wang, Shuhai Wang · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.4519 · 被引用次数：10 · 研究领域：Urinary and Genital Oncology Studies、Bladder and Urothelial Cancer Treatments、Peptidase Inhibition and Analysis

4519 Background: Nectin-4 is an adhesion molecule that is highly expressed in variety of solid tumors. Previous study of 9MW2821 has shown promising efficacy and tolerable toxicity in different advanced cancers, especially in urothelial cancer, cervical cancer, esophageal cancer and breast cancer. Here we report preliminary results of 9MW2821 combined with Toripalimab in treatment-naïve patients with la/mUC. Methods: This is an open-label, multicenter, phase 1b/2 study to evaluate the safety and efficacy of 9MW2821 combined with Toripalimab in la/mUC. Patients received 9MW2821 on D1/D8 and Toripalimab on D1, 21 days per cycle. Primary objective was safety, and secondary objectives were efficacy, pharmacokinetics and immunogenicity. Results: 40 treatment-naïve patients with la/mUC were enrolled and received the combination therapy of 9MW2821(1.25mg/kg) and Toripalimab(240mg). Median age was 66.5 years [36-78], and 73% patients were ECOG 1. 55% primary tumor sites were upper tract urothelial carcinoma. As of Dec 19, 2024, ORR was 87.5% [35/40, 95%CI 73.2-95.8], including 7.5% CR rate (comfirmed ORR was 80%). DCR was 92.5% [37/40, 95%CI 79.6-98.4]. Median PFS and DoR were not reached, 6-month PFS rate and 3-month DoR rate were 79.1% and 100%. Furthermore, ORR of subgroups in liver metastasis, bladder cancer and tumor with negative expression of Nectin-4 were 88.2%, 94.4%, 100%, respectively. These showed that different subgroups of treatment-naïve patients could benefit from the...