RC48-ADC for metastatic urothelial carcinoma with HER2-positive: Combined analysis of RC48-C005 and RC48-C009 trials.

作者：Xinan Sheng, Zhisong He, Yanxia Shi, Hong Luo, Weiqing Han, Xin Yao, Benkang Shi, Jiyan Liu, Chang-Lu Hu, Ziling Liu, Hongqian Guo, Guohua Yu, Zhigang Ji, Shiying Yu, Yi Hu, Jianming Guo, Jianming Ying, Jianmin Fang, Aiping Zhou, Jun Guo · 发表于：Journal of Clinical Oncology · 年份：2022 · DOI：10.1200/jco.2022.40.16_suppl.4520 · 被引用次数：33 · 研究领域：Bladder and Urothelial Cancer Treatments、Cancer Immunotherapy and Biomarkers、Esophageal Cancer Research and Treatment

4520 Background: RC48-ADC (Disitamab Vedotin) is a novel humanized anti-HER2 antibody-drug conjugate (ADC). RC48-ADC demonstrated a promising efficacy with a manageable safety profile in HER2-positive locally advanced or metastatic UC patients who failed to platinum based chemotherapy in RC48-C005 and RC48-C009 trials. Here are the pooled results of the two studies with the supplementary efficacy, safety and updated OS data. Methods: Both of the two trials are single-arm, multi-center, phase II trials. Eligible patients were 18̃80 years old, with central-laboratory confirmed, histologically HER2-postive (IHC2+,3+), unresectable mUC. Patients had at least one line of systemic chemotherapy. The primary endpoint was objective response rate (ORR). Progress-free survival (PFS), overall survival (OS), and safety were also assessed. Results: RC48-C005 and RC48-C009 enrolled HER2-positive locally advanced or metastatic UC patients from Nov 2017 to Sep 2020. 107 mUC patients (80 males; median age 63 y [40-79]) were enrolled. 64.5% patients had received ≥ 2 lines systemic chemotherapy. 90.7% patients had visceral metastases. As of 04 Sep 2021 (data cutoff), The overall confirmed ORR as assessed by the BIRC was 50.5% (95% CI: 40.6%, 60.3%). Similar responses were observed in prespecified subgroups. cORR was 52.1% (25/48) for patients with liver metastasis and was 55.6% (15/27) in patients with previous PD-1/L1 treatment. The cORR was 62.2% (28/45) for HER2 IHC2+&FISH+ or IHC3+ patie...