Olaptesed (NOX-A12) Alone and in Combination With Pembrolizumab in Colorectal and Pancreatic Cancer

Inclusion Criteria: 1. Written informed consent 2. Age ≥18 years 3. a) Male or female patient with a history of treated metastatic stage IV colorectal cancer with liver metastases of the primary colorectal cancer after two or more lines of prior treatment OR b) Male or female patient with a history of treated metastatic stage IV pancreatic ductal adenocarcinoma with liver metastases of the primary pancreatic cancer after one or more lines of prior treatment 4. Histologically or cytologically confirmed diagnosis of colorectal or pancreatic ductal cancer with liver metastasis 5. Measurable disease based on RECIST 1.1 as determined by the site study team 6. Expected survival of at least three months 7. Patient with liver metastasi(e)s amenable to repeated biopsies 8. Patient agreeing to repeated biopsies of metastases 9. Karnofsky performance status ≥80 % 10. a) Colorectal cancer patients that have received current standard treatment options (progression or intolerance to oxaliplatin, irinotecan, 5-fluorouracil and trifluridine/tipiracil with or without treatment combinations of cetuximab and/or bevacizumab, or ramucirumab or panitumumab, or regorafenib, including monotherapies with any of these options) OR b) Pancreatic cancer patients that have received current treatment options (progression or intolerance to combination therapies with oxaliplatinum, irinotecan, 5-fluorouracil, gemcitabine, nab-paclitaxel or erlotinib, including monotherapies with any of these options) 11. No chemotherapy treatment within the last three weeks prior to study MT Day 1 12. Resolution of toxic effect(s) of the most recent prior chemotherapy to levels deemed appropriate by the investigator; if patients have received major surgery, they must have recovered from the toxicity and/or complications from the intervention 13. The following laboratory parameters should be within the ranges specified: * Hemoglobin (Hb) ≥ 8.0 g/dL * Absolute neutrophil count (ANC) ≥ 1,000/mm³ (≥ 1.0 x 10\^9/L) * Platelets ≥ 100,000/mm³ (≥ 100 x 10\^9/L) * Creatinine ≤ 1.5 x ULN or glomerular filtration rate ≥ 60 mL/min/1.73m² * Total bilirubin ≤ 1.5 x ULN (upper limit normal) * ALT (alanine transaminase) ≤ 5 x ULN * AST (aspartate transaminase) ≤ 5 x ULN * INR (International Normalized Ratio) or PT (Prothrombin Time) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants * aPTT (Activated Partial Thromboplastin Time) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants 14. Female patients of child-bearing potential must have a negative urine or serum pregnancy test within 28 days prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Patients must agree to use an effective method of contraception or be abstinent during and for 120 days following last dose of drug (more frequent pregnancy tests may be conducted if required per local regulations) 15. Male patients must use an effective barrier method of contraception during study and for 120 days following the last dose if sexually active with a FCBP Exclusion Criteria: 1. Inability to personally provide written informed consent or to understand and collaborate throughout the study 2. Inability or unwillingness to comply with study requirements 3. Patients with metastatic lesions suitable for resection 4. Patients with metastatic cancer that have a drastic clinical progression (e.g. from Karnofsky performance 100% to 70%) within the last six weeks before screening 5. Participation in any clinical research study with administration of an investigational drug or therapy within 30 days prior to enrolment in the study 6. Use of any investigational or non-registered product (drug or vaccine) other than the study treatment 7. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or if the patient has previously participated in pembrolizumab clinical studies 8. Prior radiation therapy of tumor/metastases 9. Diagnosis of immunodeficiency or requiring concomitant chronic treatment with systemic corticosteroids or any other immunosuppressive agents within 7 days prior to the first dose of study treatment; the use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor 10. Intake of immunomodulatory medication (Type 1 interferons) 11. Prior anti-cancer monoclonal antibody (mAb) within 2 weeks prior to study MT Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to such agents administered more than 2 weeks earlier 12. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study MT Day 1 or no recovery (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent 13. Prior transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks prior to study MT Day 1 14. Live vaccine within 30 days prior to the first dose of study treatment 15. Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment 16. History of interstitial lung disease 17. History of (non-infectious) pneumonitis that required steroids or current pneumonitis 18. History of anaphylaxis or severe drug hypersensitivity reactions 19. Active infection requiring systemic therapy 20. Known to be positive for Human Immunodeficiency Virus (HIV) or other chronic infections (HBV, HCV) or with another confirmed or suspected immunosuppressive or immunodeficient condition 21. Concurrent chronic severe medical problems (heart failure, uncontrolled diabetes, bleeding disorder etc.), unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk 22. Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer 23. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis 24. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator, is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment 25. Women of childbearing potential: refusal or inability to use effective means of contraception 26. Contra-indication or known hypersensitivity to olaptesed pegol, polyethylene glycol, pembrolizumab or further ingredients to the investigational medicinal products 27. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study 28. Previous enrolment in this clinical study