Immune checkpoint inhibitors (ICIs) provide substantial benefits to a small subset of patients with advanced cancer with mismatch repair deficiency (MMRD) or microsatellite instability (MSI), including patients with pancreatic ductal adenocarcinoma (PDAC). However, the long duration of ICI treatment presents a considerable financial burden. We present the case of a 63-year-old woman with metastatic PDAC refractory to conventional chemotherapy. Genetic analyses identified an MSH6 germline mutation and a high tumor mutation burden (TMB). Complete response (CR) was achieved after a short course of low-dose nivolumab (20 mg once every 2 weeks) with chemotherapy. CR was maintained for over 1 year with low-dose nivolumab and de-escalated chemotherapy without any immune-related adverse events. This case supports the further exploration of low-dose, affordable ICI-containing regimens in patients with advanced MSI-high/TMB-high cancer.