The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer

Nature. 2021 Dec;600(7890):727-730. doi: 10.1038/s41586-021-04161-3. Epub 2021 Dec 15.


Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) amplification or overexpression occurs in approximately 20% of advanced gastric or gastro-oesophageal junction adenocarcinomas1-3. More than a decade ago, combination therapy with the anti-HER2 antibody trastuzumab and chemotherapy became the standard first-line treatment for patients with these types of tumours4. Although adding the anti-programmed death 1 (PD-1) antibody pembrolizumab to chemotherapy does not significantly improve efficacy in advanced HER2-negative gastric cancer5, there are preclinical6-19 and clinical20,21 rationales for adding pembrolizumab in HER2-positive disease. Here we describe results of the protocol-specified first interim analysis of the randomized, double-blind, placebo-controlled phase III KEYNOTE-811 study of pembrolizumab plus trastuzumab and chemotherapy for unresectable or metastatic, HER2-positive gastric or gastro-oesophageal junction adenocarcinoma22 ( , NCT03615326). We show that adding pembrolizumab to trastuzumab and chemotherapy markedly reduces tumour size, induces complete responses in some participants, and significantly improves objective response rate.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / pathology
  • Antibodies, Monoclonal, Humanized* / pharmacology
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Esophagogastric Junction / drug effects
  • Esophagogastric Junction / pathology
  • Humans
  • Programmed Cell Death 1 Receptor* / antagonists & inhibitors
  • Receptor, ErbB-2* / antagonists & inhibitors
  • Receptor, ErbB-2* / metabolism
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / metabolism
  • Stomach Neoplasms* / pathology
  • Trastuzumab* / pharmacology
  • Trastuzumab* / therapeutic use


  • Antibodies, Monoclonal, Humanized
  • Programmed Cell Death 1 Receptor
  • pembrolizumab
  • Receptor, ErbB-2
  • Trastuzumab

Associated data