Pembrolizumab, Trastuzumab, HER2 Positive Gastric Cancer

Summary

Gastric cancer is one of the major health problems worldwide, and one of the leading cause of death especially in Asia. Though the cytotoxic chemotherapy is the main treatment option, newer and molecularly targeted agents are recently incorporated to improve the survival outcome. Human epidermal growth factor receptor 2 (HER2, ErbB2) is a transmembrane tyrosine kinase receptor and is overexpressed or amplified in 10-20% of gastric cancer. Recently, Trastuzumab for Gastric Cancer (ToGA) study reported the clinical benefit of trastuzumab for HER2 positive gastric cancer patients. However, because the majority of patients develop intrinsic or acquired resistance within 1 year, elucidating the molecular mechanisms for trastuzumab resistance is warranted to improve the survival outcome of HER2 positive gastric cancer patients. A growing body of preclinical and clinical evidence shows that the immune system contributes substantially to the therapeutic effects of "monoclonal antibody, trastuzumab" in solid tumors. Pembrolizumab is a potent and highly selective humanized monoclonal antibody designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Based on strong rationale in exploring the impact of combining trastuzumab with anti-PD-1 inhibitor in HER2 positive cancer, we suggest multicenter phase IB/II study to determine antitumor activity and safety of pembrolizumab in combination with standard treatment (trastuzumab, capecitabine, and cisplatin) in patients with HER2 positive gastric cancer.

Timeline

Start

2017-02-06

Primary completion

2020-10-31

Completion

2021-10

Publications

• Jung SH, Lee CK, Kwon WS, Yun S, Jung M, Kim HS, Chung HC, Chung YJ, Rha SY. Monitoring the Outcomes of Systemic Chemotherapy Including Immune Checkpoint Inhibitor for HER2-Positive Metastatic Gastric Cancer by Liquid Biopsy. Yonsei Med J. 2023 Sep;64(9):531-540. doi: 10.3349/ymj.2023.0096.
• Lee CK, Rha SY, Kim HS, Jung M, Kang B, Che J, Kwon WS, Park S, Bae WK, Koo DH, Shin SJ, Kim H, Jeung HC, Zang DY, Lee SK, Nam CM, Chung HC. A single arm phase Ib/II trial of first-line pembrolizumab, trastuzumab and chemotherapy for advanced HER2-positive gastric cancer. Nat Commun. 2022 Oct 12;13(1):6002. doi: 10.1038/s41467-022-33267-z.

Drugs

Indications