Combined AlloStim+Anti-PD-L1 in 4L MSS Metastatic Colorectal Cancer

Inclusion Criteria:

1. Adult male and female subjects aged 18-80 years at screening visit
2. Pathologically confirmed diagnosis of MSS/pMMR colorectal adenocarcinoma
3. Presenting with metastatic disease:

   * Primary tumor can be intact or previously resected
4. Previous treatment failure of at least two lines of active systemic chemotherapy:

   * Previous chemotherapy must have included a fluoropyrimidine, oxaliplatin (e.g. FOLFOX, CAPOX), and irinotecan-containing (e.g. FOLFIRI) regimens (single regimen of FOLFIRINOX satisfies)
   * Administered in adjuvant setting or for treatment of metastatic disease
   * If KRAS wild type, must have at least one prior anti-EGFR therapy if left sided primary tumor
5. Treatment failure or refusal/not qualified for at least one third-line treatment

   * TAS-102 +/- bevacizumab or regorafenib or fruquinib
   * Treatment failure can be due to disease progression or toxicity
   * Time from last treatment failure to Informed Consent must be no more than 30 days
6. ECOG performance score: 0-1
7. Adequate hematological function:

   * Absolute granulocyte count ≥ 1,200/mm3
   * Platelet count ≥ 100,000/mm3
   * Hemoglobin ≥ 9.0 g/dL (may be corrected by transfusion)
8. Adequate Organ Function:

   * Creatinine ≤ 1.5 mg/dL
   * Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
9. Alkaline phosphatase ≤ 2.5 times ULN \*
10. Aspartate aminotransferase (AST) or (SGOT) ≤ 2.5 times ULN \*
11. Alanine aminotransferase (ALT) or (SGPT) ≤ 2.5 times ULN\*
12. EKG without clinically relevant abnormalities
13. Female subjects: Not pregnant or lactating
14. Patients with childbearing potential must have a negative ß-HCG test and agree to use a highly effective contraceptive method during the course of the study
15. Study specific Informed Consent in the native language of the subject

    * ≤ 5 times ULN if liver involvement

Exclusion Criteria:

1. High frequency microsatellite instability (MSI-H) or deficient mismatched repair dMMR
2. Bowel obstruction or high risk for obstruction if tumors become inflamed
3. Moderate or severe ascites requiring medical intervention
4. Clinical evidence of brain metastasis or leptomeningeal involvement
5. Widespread peritoneal carcinomatous (e.g. CT scan shows innumerable lesions visible and/or abnormal thickening of greater omentum) that increases risk of a major morbidity (e.g. bowel obstruction) in the opinion of the Investigator
6. COPD
7. Pulmonary lymphangitis or symptomatic pleural effusion (grade ≥ 2) that results in pulmonary dysfunction requiring active treatment; or, oxygen saturation \<92% on room air
8. Any of the following mood disorders: active major depressive episode, recent history of suicidal attempt or ideation
9. Prior allogeneic bone marrow/stem cell or solid organ transplant
10. Chronic use (\> 2 weeks) of greater than physiologic doses of a corticosteroid agent (dose equivalent to \> 5 mg/day of prednisone) planned or anticipated during the study before the end of the Safety Evaluation Period (28 days after the last dose of IP)

    * Topical corticosteroids are permitted
11. Prior diagnosis of an active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, autoimmune thyroid disease, uveitis)

    * Well controlled Type I diabetes allowed (HbA1c \< 8.5%)
12. Prior experimental immunotherapy
13. History of blood transfusion reactions
14. Progressive viral or bacterial infection

    o All infections must be resolved and the subject must remain afebrile for seven days without antibiotics prior to being placed on study
15. Cardiac disease of symptomatic nature
16. History of HIV positivity or AIDS
17. History of severe hypersensitivity to monoclonal antibody drugs
18. Psychiatric or addictive disorders or other condition that, in the opinion of the Investigator, would preclude study participation.
19. Subjects that lack ability to provide consent for themselves
20. Any prior cancer diagnosis (other than cured basal cell carcinoma, head and neck carcinoma in-situ, superficial Ta, Tis, T1 bladder cancer, or papillary carcinoma of thyroid) or concurrent cancer histologically different than colorectal adenocarcinoma