Journal Article

Efficacy and safety of a novel anti‐HER2 therapeutic antibody RC48 in patients with HER2‐overexpressing, locally advanced or metastatic gastric or gastroesophageal junction cancer: a single‐arm phase II study

Gu, Kangsheng, Li, Zhen, Shu, Yongqian, Cui, Yuehong, Gao, Chao, Ying, Jieer, Zhang, Liangming, Ba, Yi, Yang, Liuzhong, Fan, Qingxia, Xu, Ruihua, Bai, Chunmei, Sun, Yuping, Liu, Tianshu, Wang, Airong, Liang, Xinjun, Wei, Jia, Luo, Suxia, Zeng, Jiangzheng, Fang, Jianmin, Zhang, Xizhi, Xu, Jianming, Ma, Dong, Li, Enxiao, Dai, Guanghai, Shen, Lin, Fan, Nanfeng, Lu, Jianwei, Li, Shengmian, Yu, Guohua, Xu, Nong, Deng, Ting, Peng, Zhi, He, Yifu, Liu, Yong

2021

Overview

Background Current treatment options for human epidermal growth factor receptor 2 (HER2)‐overexpressing gastric cancer at third‐line have shown limited clinical benefit. Further, there is no specific treatment for HER2 immunohistochemistry (IHC) 2+ and fluorescence in‐situ hybridization‐negative patients. Here, we report the efficacy and safety of a novel anti‐HER2 antibody RC48 for patients with HER2‐overexpressing, advanced gastric or gastroesophageal junction cancer. Methods Patients with HER2‐overexpressing (IHC 2+ or 3+), locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second‐line therapy were eligible and received RC48 2.5 mg/kg alone every 2 weeks. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee. Secondary endpoints included progression‐free survival (PFS), overall survival (OS), duration of response, time to progression, disease control rate, and safety. Results Of 179 patients screened, 125 were eligible and received RC48 treatment. The ORR was 24.8% (95% confidence interval [CI]: 17.5%‐33.3%). The median PFS and OS were 4.1 months (95% CI: 3.7‐4.9 months) and 7.9 months (95% CI: 6.7‐9.9 months), respectively. The most frequently reported adverse events were decreased white blood cell count (53.6%), asthenia (53.6%), hair loss (53.6%), decreased neutrophil count (52.0%), anemia (49.6%), and increased aspartate aminotransferase level (43.2%). Serious adverse events (SAEs) occurred in 45 (36.0%) patients, and RC48‐related SAEs were mainly decreased neutrophil count (3.2%). Seven patients had adverse events that led to death were not RC48‐related. Conclusions RC48 showed promising activity with manageable safety, suggesting potential application in patients with HER2‐overexpressing, advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy. RC48 is safe and efficacious for HER2‐overexpressing gastric cancer patients. Patients received trastuzumab showed similar efficacy with trastuzumab‐naïve patients. HER2 status doesn't have significant effect on clinical outcomes.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Antibodies / Antibodies, Monoclonal, Humanized / antibody‐drug conjugate / Cancer therapies / Chemotherapy / Disease control / Documentation / Drug dosages / Drug withdrawal / Epidermal growth factor / Esophagogastric Junction / FDA approval / Gastric cancer / HER2‐overexpressing / Humans / Immunotherapy / Metastasis / Original / Patients / phase II clinical trial / Radiation therapy / RC48 / Receptor, ErbB-2 - genetics / Response rates / Stomach Neoplasms - drug therapy / Stomach Neoplasms - genetics / third‐line therapy / Tumors / Vaccines