TLR9 Immunotherapy for Peritoneal Carcinomatosis

Inclusion Criteria: * Patients eligible for inclusion in this study must meet all of the following criteria: 1. Male or female patients age ≥ 18 years of age at the time of informed consent 2. Must be able to provide written informed consent, stating an understanding of the procedures and investigational nature of the study treatment, and willingness to comply with study requirements 3. Must have documented CRC or appendiceal adenocarcinoma peritoneal carcinomatosis or malignant ascites. Primary tumor may be intact and limited liver and/or lung disease is permitted 4. Must have evaluable disease by physical examination, serum tumor markers, radiologic assessment, or laparoscopic visual assessment 5. Must have a life expectancy of ≥ 12 weeks as estimated by the investigator 6. Must have an ECOG status of ≤ 2 7. Patients with acceptable laboratory values defined as: * Estimated creatinine clearance (calculated using Cockcroft-Gault formula, or measured) ≥ 60 mL/min, not dialysis dependent * Total bilirubin ≤ 1.5 mg/dl, unless elevated bilirubin is clearly related to Gilbert syndrome (and total bilirubin \< 6.0 mg/dl) * Alanine aminotransferase (ALT) ≤ 3.5 x upper limit of normal (ULN) * Aspartate aminotransferase (AST) ≤ 3.5 x ULN * Absolute neutrophil count \> 1.0 x 109/L (must be independent of blood product administration) * Platelet count \> 100 x 109/L (must be independent of blood product administration) * Hemoglobin ≥ 8 g/dL (must be independent of blood product administration) 8. Surgically sterile patients or patients of childbearing potential (CBP) who agree to use highly effective methods of contraception during study dosing and for 6 months after last dose of study drug 9. All other relevant medical conditions must be well-managed and stable, in the opinion of the investigator, for at least 28 days prior to administration of study drug Exclusion Criteria: 1. Has received prior TLR9 therapy 2. Has received chemotherapy, radiotherapy, or biological cancer therapy within 21 days or 5 half-lives (whichever is shorter) of the start of treatment 3. Has received an investigational agent within 28 days of the start of treatment 4. Has received a commercial vaccine (flu, COVID, etc.) within 2 weeks of C1D1 5. Has any unresolved toxicity ≥ Grade 2 from previous anti-cancer therapy, except for stable chronic toxicities (≤ Grade 3) that are not expected to resolve 6. Has a history of histologically confirmed metastases outside of the peritoneal cavity, liver, or lungs 7. Has high volume liver or lung metastases, defined as \> 50% replacement of the liver volume by metastatic disease or \> 5 lung lesions greater than 1 cm in size 8. Tumor causing biliary obstruction not amenable to stenting or percutaneous drainage 9. Ongoing or untreated intra-abdominal infection or bowel obstruction 10. Has known, clinically active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV) (Note: Testing is not required) 11. Receiving continuous systemic corticosteroid therapy (≥ 10 mg/day of prednisolone or equivalent) 12. Clinically significant cardiac disease or impaired cardiac function, including any of the following: * A history of newly diagnosed transmural myocardial infarction, cerebral infarction, or pulmonary embolism within 6 months, except those approved by the medical monitor * A history of newly diagnosed deep vein thrombosis (DVT) within 3 months * Left ventricular ejection fraction (LVEF) \< 50% * QTc \>480 msec 13. Active bacterial, viral, or fungal infection: patients with ongoing use of prophylactic antibiotics, antiviral agents, or antifungal agents remain eligible as long as there is no evidence of active infection 14. Other active malignancy within 2 years excluding cutaneous squamous or basal cell carcinomas 15. Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results 16. History of hypersensitivity to TLR9 agonists 17. Pregnant, likely to become pregnant, or lactating women (where pregnancy is defined as the state of a female after conception and until the termination of gestation)