Background: Colorectal cancer (CRC) is one of the few cancers in which aggressive local approaches to treat systemic metastases have resulted in clinical benefit. Despite these approaches 70-80% of patients (pts) with resectable metastatic disease will recur. The one-year recurrence rate for this population is ~40-50%. Immunotherapeutics have yet to be studied in this setting. To sensitize microsatellite stable (MSS) CRCs to immune therapies adjunctive therapies are required. Gross tumor microenvironments suppress systemic anti-cancer immune responses. Stereotactic body radiation therapy (SBRT) is commonly utilized to treat liver metastatic CRC, using very high doses of focused radiation to ablate tumors. This causes localized inflammation, a potential increase in immunogenic intra-tumoral and intra-lymphatic antigen release, and a rapid influx of responding immune cells. We hypothesize that radiotherapy-induced tumor necrosis, and surgical removal of the remaining immunosuppressive gross disease will enhance the immunogenicity of CRC and potentiate the effectiveness of PD-1 blockade. Methods: This is a single arm phase 1b investigator-initiated study (NCT02837263) to evaluate the use of pem in combination with ablative radiotherapy for the treatment of oligometastatic CRC. This study examines the sequential use of SBRT, then pem followed by resection of all known sites of disease and 6 months of adjuvant pem. Pts with MSS CRC with resectable liver metastatic disease who have received prior FOLFOX are eligible. The primary endpoints are safety/tolerability and the rate of cancer recurrence at 1 year. Secondary endpoints include time to disease recurrence, disease free survival and overall survival. This study is currently enrolling with a planned total accrual of 15 patients. Correlative studies examine PD-L1 status, tumor infiltrating lymphocytes, evidence of an abscopal effect, versican proteolysis as a novel immune biomarker, and the ability of multiparametric fluorodeoxyglucose (FDG) PET MR and fluorothymidine (FLT) PET CT to detect immune infiltration. Clinical trial information: NCT02837263