Background: Adjunctive therapies are essential to enhance the effect of anti-PD1 therapies for the treatment of microsatellite stable (MSS) colorectal cancer. SBRT is utilized to treat liver metastatic CRC, causing an increase in immunogenic intra-tumoral and intra-lymphatic antigen release and a rapid influx of responding immune cells. We hypothesize that radiation enhances the immunogenicity of MSS CRC and potentiates the effectiveness of PD-1 blockade. This phase Ib study examines the safety and efficacy of the sequential combination of SBRT and Pem in patients for whom the goal is to resect all sites of known disease. Methods: Key eligibility criteria include MSS CRC with liver-confined metastatic disease with the therapeutic goal of resection of all radiographic disease with one operation. Subjects must be a candidate for SBRT to 1-3 liver metastases. Prior surgery and systemic chemotherapy are allowed. Subjects receive sequential SBRT and cycle 1 of Pem prior to operative management. Postoperatively, patients complete cycles 2-9 of Pem followed by scheduled surveillance with imaging every 12 weeks. The primary objectives are to determine the safety/tolerability of this regimen and the recurrence rate at 1 year following clearance of metastatic disease. Secondary objectives include time to recurrence, DFS, and OS. Results: 10 patients (median age 61.5 [range 39-69]) have been enrolled and completed the intended neoadjuvant therapy, operative management and at least 4 adjuvant cycles of Pem. All patients had received prior FOLFOX. SBRT median dose was 50 Gy (40-60 Gy) to a single lesion targeted in all patients. Mean gross tumor size targeted was 19.1cc (2.3-80.4). Any-grade post-operative AEs (>20%) attributable to Pem include diarrhea (30%), hyperbilirubinemia (20%%), and leukopenia (20%). Post-operative AEs included one case of biliary tract injury and biloma, not related to immunotherapy. No grade 3/4 immunotherapy AEs have occurred. Conclusions: The combination of SBRT with Pem and surgical resection is well tolerated with no signal of increased immunotherapy-related toxicity in the post-operative setting. Clinical trial information: NCT02837263