Long-term control of peritoneal metastases following claudin 18.2-targeted CAR T-Cell therapy in advanced gastric cancer

Abstract

Gastric cancer with peritoneal metastasis has a poor prognosis and limited treatment options. Claudin 18.2 (CLDN18.2) CAR T therapy has shown activity in advanced gastric cancer, but its role in peritoneal disease remains insufficiently characterized. Here, we report three patients with gastric cancer and peritoneal metastasis from a phase I trial of satri-cel (NCT03874897), all with high CLDN18.2 expression. All three patients experienced clinical and radiologic benefit after treatment and achieved durable peritoneal disease control. After CLDN18.2-targeted CAR T-cell therapy, one patient underwent conversion surgery 8 months after infusion. After resection of subsequent bilateral ovarian metastases, no further disease progression was observed, corresponding to long-term control of peritoneal metastases. The other two patients achieved overall survival of 44 and 35 months, respectively. Although circulating CAR T-cells became nearly undetectable in peripheral blood by around day 30 after infusion, CAR T-cell infiltration was still detected in resected gastric or ovarian tumor tissues months later. These findings support substantial and durable activity of CLDN18.2 CAR T-cell therapy in gastric cancer with peritoneal metastasis.