Safety and Activity of PolyPEPI1018 Plus Atezolizumab in Colorectal Cancer.

This is a multicenter, open label, phase II trial to determine the safety, tolerability, and immunogenicity and initial clinical activity of the combination treatment of PolyPEPI1018 vaccine and atezolizumab in participants with MSS CRC who have progressed on 2 or 3 prior regimens.

Inclusion Criteria: 1. Provide written informed consent for the trial. 2. Adults 18 years or older on the day of signing informed consent. 3. Histologically or cytologically confirmed CRC that is metastatic. 4. Primary and/or metastatic tumor(s) that is known to be MSS as determined locally 5. Must have had 2-3 prior lines of therapy for CRC in the advanced or metastatic setting, including all of the following in the absence of contraindications: a) fluoropyrimidine, b) oxaliplatin, c) irinotecan, d) one or more biologics depending on the clinical scenario. Prior regorafenib and/or TAS-102 are allowed but not required. Note: a line of therapy is generally considered \>2 weeks of exposure to the same regimen followed by radiographically documented progression. Agents that are mechanistically similar (e.g. 5-fluorouracil and capecitabine) and are used interchangeably due to tolerability but not progression may be considered as components of the same regimen upon discussion with the medical monitor. 6. Willingness to undergo biopsy prior to study therapy and after approximately 6 weeks of study therapy. If biopsy on study is not feasible, then archival tissue must be available from within 90 days of signing consent. 7. Willingness to undergo buccal swab prior to study therapy for the determination of HLA profile. 8. Documented radiographic progression after the last regimen prior to entry on this study. 9. Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions can only be considered as measurable disease if disease progression has been unequivocally documented at that site since radiation. 10. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 11. Adequate organ functions as defined by the following laboratory parameters at baseline (laboratory parameters outside of these ranges that are deemed clinically insignificant should be discussed with the medical monitor): 1. Absolute neutrophil count ≥1.5 x 109/L; 2. Hemoglobin ≥9 g/dL: transfusion to achieve this cutoff is not allowed within 14 days of first dose of study therapy; 3. Platelet count ≥100,000/mm3; 4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN) - ASL and/or ALT may be ≤5 x ULN in the setting of liver metastases; 5. Total bilirubin ≤ 1.5 x institutional ULN; 6. Serum creatinine within normal limits or calculated creatinine clearance \>60 mL/min/1.73 m2 using the Cockroft-Gault method (Appendix 2) for participants with serum creatinine levels above or below the institutional normal range; 7. Albumin ≥3.0 g/dL; 8. Acceptable coagulation parameters including international normalized ratio (INR) \