Open AccessEfficacy 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
Author(s) -
Peng Zhi,
Liu Tianshu,
Wei Jia,
Wang Airong,
He Yifu,
Yang Liuzhong,
Zhang Xizhi,
Fan Nanfeng,
Luo Suxia,
Li Zhen,
Gu Kangsheng,
Lu Jianwei,
Xu Jianming,
Fan Qingxia,
Xu Ruihua,
Zhang Liangming,
Li Enxiao,
Sun Yuping,
Yu Guohua,
Bai Chunmei,
Liu Yong,
Zeng Jiangzheng,
Ying Jieer,
Liang Xinjun,
Xu g,
Gao Chao,
Shu Yongqian,
Ma Dong,
Dai Guanghai,
Li Shengmian,
Deng Ting,
Cui Yuehong,
Fang Jianmin,
Ba Yi,
Shen Lin
Publication year - 2021
Publication title -
cancer communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.119
H-Index - 53
ISSN - 2523-3548
DOI - 10.1002/cac2.12214
Subject(s) - medicine , adverse effect , gastroenterology , cancer , anemia , clinical endpoint , phases of clinical research , oncology , surgery , chemotherapy , clinical trial
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.