Safety and efficacy of perioperative dual PD-1 and HER2 blockade in HER2-positive gastric cancer.

The use of trastuzumab and programmed death-1 (PD-1) inhibitor is effective in patients with HER2-positive advanced gastric or gastro-esophageal junction cancer; however, their use has not been investigated in patients with localized disease. This phase 2 trial evaluates the safety and efficacy of dual PD-1 (sintilimab) and HER2 blockade with chemotherapy in patients with resectable HER2-positive gastric and gastro-esophageal junction adenocarcinoma. 22 patients are enrolled, and 20 patients undergo surgery. The primary endpoint is achieved; 12 (55%, 95% confidence interval [CI]: 32-76) of 22 patients have a major pathological response, and 11 (50%, 95% CI: 28-72) of 22 patients achieve pathological complete response. The most common grade 3 treatment-related adverse events are neutropenia and thrombocytopenia. No treatment-related deaths occur. Transcriptomic analysis, bioinformatics analysis, and immunofluorescence staining demonstrate that regulatory T cells are associated with possibility of drug resistance. This study was registered at the Chinese Clinical Trial Registry (identifier: ChiCTR2200058732).