Immunotherapy-based monotherapy treatment in metastatic pancreatic ductal adenocarcinoma (mPDAC) has shown limited benefit outside of the mismatch repair deficiency setting, while safety and efficacy of combining dual-checkpoint inhibitor immunotherapy with chemotherapy remains uncertain. Here, we present results from the CCTG PA.7 study (NCT02879318), a randomized phase II trial comparing gemcitabine and nab-paclitaxel with and without immune checkpoint inhibitors durvalumab and tremelimumab in 180 patients with mPDAC. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and objective response rate. Results of the trial were negative as combination immunotherapy did not improve survival among the unselected patient population (p = 0.72) and toxicity was limited to elevation of lymphocytes in the combination immunotherapy group (p = 0.02). Exploratory baseline circulating tumor DNA (ctDNA) sequencing revealed increased survival for patients with KRAS wildtype tumors in both the combination immunotherapy (p = 0.001) and chemotherapy (p = 0.004) groups. These data support the utility of ctDNA analysis in PDAC and the prognostic value of ctDNA-based KRAS mutation status.