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

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, 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

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.

Trial registration: ClinicalTrials.gov NCT03556345.

Keywords: HER2-overexpressing; RC48; antibody-drug conjugate; gastric cancer; phase II clinical trial; third-line therapy.

Conflict of interest statement

JF is employee and shareholder of RemeGen, Ltd. All the other authors declare no conflict of interest.

© 2021 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.

Figures

FIGURE 1
FIGURE 1
Flow diagram of study enrollment, treatment, and outcomes. *One patient agree to quit the trial due to the rapid progression of the tumor, short expected survival, and limited potential benefit from RC48
FIGURE 2
FIGURE 2
Treatment responses of 125 Chinese patients with HER2‐overexpressing, locally advanced or metastatic gastric cancer treated with RC48. A, Waterfall plot of best objective response assessed by IRC. B, Spider plot of best objective response assessed by IRC. Dots indicate the IRC assessment time points. Dashed lines at ‐30% or 20% indicate the minimum change in tumor size for a PR or PD respectively by RECIST 1.1. Non‐responders indicate the patients with SD or PD. Responders indicate the patients with PR. Abbreviations: IRC independent review committee, PR partial response, SD stable disease, PD progression disease, NE not evaluable, RECIST Response Evaluation Criteria In Solid Tumors, HER2 human epidermal growth factor receptor 2
FIGURE 3
FIGURE 3
Kaplan‐Meier curves of progression‐free survival and overall survival for the 125 Chinese patients with HER2‐overexpressing, locally advanced or metastatic gastric cancer treated with RC48. A, The estimated progression‐free survival in all patients was 4.1 months (95% CI, 3.7‐4.9 months). B, The estimated overall survival in all patients was 7.9 months (95% CI, 6.7‐9.9 months). Abbreviations: HER2 human epidermal growth factor receptor 2, CI confidence interval

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Source: PubMed

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