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

Prior treatment

• Prior allogeneic bone marrow/stem cell or solid organ transplant
• 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
• Prior experimental immunotherapy
• 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

Other illness

• Any of the following mood disorders: active major depressive episode, recent history of suicidal attempt or ideation
• History of blood transfusion reactions
• Cardiac disease of symptomatic nature
• History of HIV positivity or AIDS
• History of severe hypersensitivity to monoclonal antibody drugs
• Psychiatric or addictive disorders or other condition that, in the opinion of the Investigator, would preclude study participation.
• 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

Lab values

• 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%)

Other

• High frequency microsatellite instability (MSI-H) or deficient mismatched repair dMMR
• Bowel obstruction or high risk for obstruction if tumors become inflamed
• Moderate or severe ascites requiring medical intervention
• Clinical evidence of brain metastasis or leptomeningeal involvement
• 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
• COPD
• Pulmonary lymphangitis or symptomatic pleural effusion (grade ≥ 2) that results in pulmonary dysfunction requiring active treatment; or, oxygen saturation <92% on room air
• Subjects that lack ability to provide consent for themselves

• Adult male and female subjects aged 18-80 years at screening visit
• Pathologically confirmed diagnosis of MSS/pMMR colorectal adenocarcinoma
• Presenting with metastatic disease:
  • Primary tumor can be intact or previously resected
• 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
• 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
• ECOG performance score: 0-1
• Adequate hematological function:
  • Absolute granulocyte count ≥ 1,200/mm3
  • Platelet count ≥ 100,000/mm3
  • Hemoglobin ≥ 9.0 g/dL (may be corrected by transfusion)
• Adequate Organ Function:
  • Creatinine ≤ 1.5 mg/dL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 times ULN *
• Aspartate aminotransferase (AST) or (SGOT) ≤ 2.5 times ULN *
• Alanine aminotransferase (ALT) or (SGPT) ≤ 2.5 times ULN*
• EKG without clinically relevant abnormalities
• Female subjects: Not pregnant or lactating
• 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
• Study specific Informed Consent in the native language of the subject
  • ≤ 5 times ULN if liver involvement