Treatment-related adverse events of grade ≥3 were reported in 31.3% of patients.<h4>Conclusion</h4>Neoadjuvant RC48 combined with camrelizumab and S-1 showed potential antitumour activity with an acceptable safety profile in HER2-overexpressing locally advanced resectable G/GEJ adenocarcinoma.<h4>Key points</h4>Neoadjuvant RC48 plus camrelizumab and S-1 showed encouraging pathological responses in HER2-overexpressing gastric cancer. This evidence concerns the gene ERBB2 and adenocarcinoma.