Pembrolizumab, Trastuzumab, HER2 Positive Gastric Cancer
Status:
Active, not recruiting
Trial end date:
2021-10-01
Target enrollment:
Participant gender:
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.