Neoadjuvant camrelizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastroesophageal junction adenocarcinoma: a single-arm, phase 2 trial

Background The impact of neoadjuvant combined chemotherapy, immunotherapy, and targeted therapy on pathologic responses and survival outcomes in HER2-positive locally advanced gastric cancer remains unclear. Patients and Methods In this single-arm, phase 2 trial, patients with HER2-positive resectable cT4 and/or N + M0 gastric or gastroesophageal junction (G/GEJ) adenocarcinoma received four cycles of neoadjuvant camrelizumab plus trastuzumab and CapOx, followed by D2 gastrectomy and four cycles of CapOx. The primary endpoint was pathological complete response (pCR, ypT0N0) rate. Results Twenty-five patients were enrolled and received neoadjuvant combination treatment. Of these patients, 11 (44%) were in cT3 and 14 (56%) in cT4a; all had positive nodal status. Of the 23 patients who underwent surgery, 5 (21.7%, 95% CI: 7.5-43.7) achieved pCR (ypT0N0), and 7 (30.4%, 95% CI: 13.2-52.9) achieved near pCR (ypT0). The R0 resection rate was 100%. During a median follow-up of 41.0 months, no patients with pCR had recurrence or death. In contrast, five of 18 patients with non-pCR had recurrence, and four of them died. The three-year disease-free survival rate was 78.3%. During neoadjuvant treatment, grade 3 adverse events were observed in 36% of patients, with no grade 4 or 5 adverse events reported. No treatment-related surgical delay or reoperation occurred. Conclusion Neoadjuvant camrelizumab plus trastuzumab and chemotherapy demonstrated favorable response and tolerable safety in HER2-positive G/GEJ adenocarcinoma.