111 Background: MSI-H/dMMR and POLE mutation had been proven to be predictive of response to PD-1 blockade in metastatic colorectal cancer. However, reported response rates are often < 50%. Several preclinical studies reported COX inhibitor improve antigen presentation and T-cell infiltration in tumors. We investigated the efficacy of PD-1 blockade combined with COX inhibitor in colorectal cancer patients with MSI-H/dMMR or POLE mutation. Methods: PCOX was a prospective, single arm, phase II study. Patients with MSI-H/dMMR or POLE mutation advanced or metastatic colorectal cancer received PD-1 blockade (pembrolizumab 200mg, q3w; or BAT 1306 100mg, q3w; or nivolumab 3mg per kilogram, q2w) plus COX inhibitor (celebrex 400mg or aspirin 200mg, p.o. qd). The primary endpoint was ORR, secondary endpoints included PFS, OS and safety. Results: Totally 24 patients were enrolled. 14(58.3%) patients were female. Median age was 41.5-years-old. Among 24 patients, 5(20.8%) patients were chemotherapy-naïve, 11(45.8%) patients had first line chemotherapy failed and 8(33.3%) patients had at least second lines chemotherapy failed. 22 patients were MSI-H/dMMR and 2 patients were with POLE mutation. At a median follow-up of 14.5 months, the ORR was 83.3% (20/24), including 5 patients achieved CR (3 pCR and 2 cCR). 3 patients achieved SD and 1 patient was PD. Median PFS and OS was not yet reached. One-year PFS rates was 80.7% (95%CI, 63.5%-97.9%). One-year survival rates was 91.3% (95%CI, 79.7%-100%). The reported treatment-related adverse events were listed in table below. Conclusions: The combination of PD-1 blockade plus COX inhibitor was associated with higher response rates in advanced or metastatic colorectal cancer patients with MSI-H/dMMR or POLE mutation than anti-PD-1 alone as historical controls. Clinical trial information: NCT03638297. [Table: see text][Table: see text]