Disulfiram Plus Nivolumab in Patients with Advanced Gastric Cancer: An Open-Label Phase I Trial

Tumor-associated macrophages correlate with poor prognosis and resistance to immune checkpoint inhibitor therapy in cancer patients. Disulfiram, a drug for alcoholism treatment, has been identified as an inhibitor for FROUNT, which facilitates chemokine-mediated macrophage accumulation to tumor sites. A combination of disulfiram with a PD-1 antibody synergistically inhibits tumor progression in the mouse model. Here, we performed the single-cell transcriptome analysis of gastric cancer specimens before and after treatment with disulfiram plus nivolumab. We explored the immunophenotypical features associated with the response to the treatment. Overall design: Thirteen patients with gastric cancer were treated with orally administered disulfiram of 160mg 3 times daily for 28 days with intravenous nivolumab 240 mg/body every two weeks with one cycle as four weeks until disease progression or up to six cycles. Specimens were collected once before and after the end of the treatment.