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

Abstract 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‐neg...

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Autores principales:	Zhi Peng, Tianshu Liu, Jia Wei, Airong Wang, Yifu He, Liuzhong Yang, Xizhi Zhang, Nanfeng Fan, Suxia Luo, Zhen Li, Kangsheng Gu, Jianwei Lu, Jianming Xu, Qingxia Fan, Ruihua Xu, Liangming Zhang, Enxiao Li, Yuping Sun, Guohua Yu, Chunmei Bai, Yong Liu, Jiangzheng Zeng, Jieer Ying, Xinjun Liang, Nong Xu, Chao Gao, Yongqian Shu, Dong Ma, Guanghai Dai, Shengmian Li, Ting Deng, Yuehong Cui, Jianmin Fang, Yi Ba, Lin Shen
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	antibody‐drug conjugate gastric cancer HER2‐overexpressing phase II clinical trial RC48 third‐line therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/84d42b69d5e24a3c9b4936b33833bf96
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spelling	oai:doaj.org-article:84d42b69d5e24a3c9b4936b33833bf962021-11-27T06:05:32ZEfficacy 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 study2523-354810.1002/cac2.12214https://doaj.org/article/84d42b69d5e24a3c9b4936b33833bf962021-11-01T00:00:00Zhttps://doi.org/10.1002/cac2.12214https://doaj.org/toc/2523-3548Abstract 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.Zhi PengTianshu LiuJia WeiAirong WangYifu HeLiuzhong YangXizhi ZhangNanfeng FanSuxia LuoZhen LiKangsheng GuJianwei LuJianming XuQingxia FanRuihua XuLiangming ZhangEnxiao LiYuping SunGuohua YuChunmei BaiYong LiuJiangzheng ZengJieer YingXinjun LiangNong XuChao GaoYongqian ShuDong MaGuanghai DaiShengmian LiTing DengYuehong CuiJianmin FangYi BaLin ShenWileyarticleantibody‐drug conjugategastric cancerHER2‐overexpressingphase II clinical trialRC48third‐line therapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancer Communications, Vol 41, Iss 11, Pp 1173-1182 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibody‐drug conjugate gastric cancer HER2‐overexpressing phase II clinical trial RC48 third‐line therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	antibody‐drug conjugate gastric cancer HER2‐overexpressing phase II clinical trial RC48 third‐line therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Zhi Peng Tianshu Liu Jia Wei Airong Wang Yifu He Liuzhong Yang Xizhi Zhang Nanfeng Fan Suxia Luo Zhen Li Kangsheng Gu Jianwei Lu Jianming Xu Qingxia Fan Ruihua Xu Liangming Zhang Enxiao Li Yuping Sun Guohua Yu Chunmei Bai Yong Liu Jiangzheng Zeng Jieer Ying Xinjun Liang Nong Xu Chao Gao Yongqian Shu Dong Ma Guanghai Dai Shengmian Li Ting Deng Yuehong Cui Jianmin Fang Yi Ba Lin Shen 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
description	Abstract 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.
format	article
author	Zhi Peng Tianshu Liu Jia Wei Airong Wang Yifu He Liuzhong Yang Xizhi Zhang Nanfeng Fan Suxia Luo Zhen Li Kangsheng Gu Jianwei Lu Jianming Xu Qingxia Fan Ruihua Xu Liangming Zhang Enxiao Li Yuping Sun Guohua Yu Chunmei Bai Yong Liu Jiangzheng Zeng Jieer Ying Xinjun Liang Nong Xu Chao Gao Yongqian Shu Dong Ma Guanghai Dai Shengmian Li Ting Deng Yuehong Cui Jianmin Fang Yi Ba Lin Shen
author_facet	Zhi Peng Tianshu Liu Jia Wei Airong Wang Yifu He Liuzhong Yang Xizhi Zhang Nanfeng Fan Suxia Luo Zhen Li Kangsheng Gu Jianwei Lu Jianming Xu Qingxia Fan Ruihua Xu Liangming Zhang Enxiao Li Yuping Sun Guohua Yu Chunmei Bai Yong Liu Jiangzheng Zeng Jieer Ying Xinjun Liang Nong Xu Chao Gao Yongqian Shu Dong Ma Guanghai Dai Shengmian Li Ting Deng Yuehong Cui Jianmin Fang Yi Ba Lin Shen
author_sort	Zhi Peng
title	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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/84d42b69d5e24a3c9b4936b33833bf96
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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

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