{
    "info": {
        "nct_id": "NCT05492682",
        "official_title": "A Study to Evaluate the Safety and Immune Activity of PeptiCRAd-1 in Combination With Pembrolizumab in Patients With Injectable Solid Tumors in Indications Known to Express NY-ESO-1 and MAGE-A3",
        "inclusion_criteria": "1. Written informed consent.\n2. Male or female, ≥18 years of age.\n3. Patients with any 1 of the following histologically confirmed tumors and who qualifies for new or continued CPI therapy and relapsing to/after standard therapy or the patient has refused or does not tolerate standard therapy:\n\n   * Inoperable/metastatic cutaneous malignant melanoma\n   * Relapsed or newly diagnosed locally advanced inoperable/metastatic TNBC\n   * Inoperable advanced/metastatic non-squamous NSCLC\n   * Inoperable and/or advanced Synovial or myxoid round cell sarcoma\n   * Inoperable and/or advanced osteosarcoma\n   * Inoperable and/or advanced colorectal cancer, patients assessed as positive for NY-ESO-1 or MAGE-A3 expression at baseline\n   * Inoperable and/or advanced/metastatic sarcoma, patients assessed as positive for NY-ESO-1 or MAGE-A3 expression at baseline\n4. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.\n5. Tumor lesion which is deemed feasible for biopsy and injection\n6. ECOG/WHO performance status 0 to 1.\n7. Acceptable liver and renal function, defined as:\n\n   * Total bilirubin ≤1.5 x upper limit of normal (ULN; does not include patients with Gilbert's Disease), and\n   * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 x ULN, and\n   * Serum creatinine ≤1.5 x ULN\n8. Acceptable hematological function, defined as:\n\n   * Hemoglobin ≥9 g/dL, and\n   * Neutrophils ≥1.5 x 109/L, and\n   * Platelet count ≥100 x 109/L Patients may be transfused to meet the hemoglobin entry criteria.\n9. Acceptable coagulation status defined by international normalized ratio (INR) of blood clotting, prothrombin time and activated partial thromboplastin time within ≤1.5 x upper limit of normal.\n10. Negative pregnancy test at screening in all women of childbearing potential (WOCBP). Such patients must agree to use a highly effective method of contraception (Appendix 1) during study intervention and for 3 months after the last virus treatment, 4 months after the last dose of pembrolizumab, and 12 months after CPO dosing. Male patients and male partners of female patients must also use barrier contraception, i.e., condom, for the time periods specified for WOCBP, plus a further 3 month period.\n\n    Urine pregnancy tests should have a sensitivity of at least 25 mIU/mL for human chorionic gonadotropin (hCG). If the urine test is positive, it must be followed by a quantitative analysis of hCG concentration in blood.\n11. Prior therapy with an immune CPI is allowed provided a 6-week washout period is observed for patients with prior programmed cell death (PD)1 or PDL1 treatment\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Receipt of any oncolytic virus treatment, or administration of a vaccine containing live virus within 4 weeks before Day 1.\n2. Use of significant immunosuppressive medication, including high dose corticosteroid (defined as the equivalent of >10 mg/day prednisone) within 4 weeks before Day 1. Inhaled or topical corticosteroid use is allowed.\n3. Prior or concomitant radiotherapy within 4 weeks before Day 1.\n4. Participation in a study with an investigational drug or device within 4 weeks prior to Day 1.\n5. Active bacterial, viral, or fungal infection that requires systemic therapy.\n6. Active autoimmune disease that has required systemic treatment in the past two years.\n7. Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the patient, if included in this study.\n8. Any concomitant medical condition requiring receipt of a therapeutic anticoagulant that, in the opinion of the treating physician, cannot safely be withheld to allow for repeated injection of PeptiCRAd 1 and tumor biopsies.\n9. Known infection with human immunodeficiency virus, hepatitis B, or hepatitis C or active tuberculosis.\n10. Known active central nervous system metastases. Patients with leptomeningeal disease, carcinomatous meningitis, symptomatic brain metastases, or radiographic signs of CNS hemorrhage are excluded.\n\n    Note: Participants with asymptomatic brain metastases (i.e. off corticosteroids and anticonvulsants for at least 7 days) are permitted.\n11. Any prior severe AE according to Common Terminology Criteria for Adverse Events (CTCAE), severe hypersensitivity reaction attributed to prior anti-PD1 or PDL1 therapy or components of the study intervention or has a history of any contraindication that, in the investigator's opinion, would contraindicate pembrolizumab administration such as:\n\n    * Resolution of side effect of prior anti-PD1 or PDL1 therapy to Grade 1\n    * Grade 2 or higher pneumonitis\n    * Grade 4 AST or ALT elevation\n    * Grade 3 or higher colitis attributable to immunotherapy Note: in the absence of clinical symptoms of pancreatitis, elevations of amylase or lipase are not contraindications to therapy on this trial.\n12. History of or planned tissue / organ transplant.\n13. Females who are pregnant or breast feeding or expecting to conceive within the projected duration of the study starting with the screening visit or males expecting to father children within the projected duration of the study starting with the screening visit.\n14. Unwillingness or inability to comply with the study protocol for any reason.\n15. Admission to an institution by virtue of an order issued by the judicial or administrative authorities.\n16. Sponsor or Contract Research Organization employees, or employees under the direct supervision of the investigator or the investigational sites and/or involved directly in the study.\n17. Prior or concurrent malignancy, unless the natural history or treatment of the disease does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Written informed consent.",
            "criterions": [
                {
                    "exact_snippets": "Written informed consent.",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "form",
                            "expected_value": "written"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Male or female, ≥18 years of age.",
            "criterions": [
                {
                    "exact_snippets": "Male or female",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "≥18 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients with any 1 of the following histologically confirmed tumors and who qualifies for new or continued CPI therapy and relapsing to/after standard therapy or the patient has refused or does not tolerate standard therapy:",
            "criterions": [
                {
                    "exact_snippets": "histologically confirmed tumors",
                    "criterion": "tumor histology",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "qualifies for new or continued CPI therapy",
                    "criterion": "CPI therapy qualification",
                    "requirements": [
                        {
                            "requirement_type": "qualification",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "relapsing to/after standard therapy",
                    "criterion": "relapse after standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "relapse",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patient has refused or does not tolerate standard therapy",
                    "criterion": "standard therapy tolerance or refusal",
                    "requirements": [
                        {
                            "requirement_type": "tolerance or refusal",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Inoperable/metastatic cutaneous malignant melanoma",
            "criterions": [
                {
                    "exact_snippets": "Inoperable/metastatic cutaneous malignant melanoma",
                    "criterion": "cutaneous malignant melanoma",
                    "requirements": [
                        {
                            "requirement_type": "operability",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "metastasis",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Relapsed or newly diagnosed locally advanced inoperable/metastatic TNBC",
            "criterions": [
                {
                    "exact_snippets": "Relapsed or newly diagnosed",
                    "criterion": "disease status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "relapsed",
                                "newly diagnosed"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "locally advanced inoperable/metastatic",
                    "criterion": "disease stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "locally advanced inoperable",
                                "metastatic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "TNBC",
                    "criterion": "cancer type",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "TNBC"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Inoperable advanced/metastatic non-squamous NSCLC",
            "criterions": [
                {
                    "exact_snippets": "Inoperable",
                    "criterion": "operability",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "inoperable"
                        }
                    ]
                },
                {
                    "exact_snippets": "advanced/metastatic",
                    "criterion": "cancer stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "advanced",
                                "metastatic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "non-squamous NSCLC",
                    "criterion": "cancer type",
                    "requirements": [
                        {
                            "requirement_type": "subtype",
                            "expected_value": "non-squamous NSCLC"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Inoperable and/or advanced Synovial or myxoid round cell sarcoma",
            "criterions": [
                {
                    "exact_snippets": "Inoperable",
                    "criterion": "operability",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "inoperable"
                        }
                    ]
                },
                {
                    "exact_snippets": "advanced",
                    "criterion": "stage",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "advanced"
                        }
                    ]
                },
                {
                    "exact_snippets": "Synovial or myxoid round cell sarcoma",
                    "criterion": "cancer type",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "Synovial sarcoma",
                                "myxoid round cell sarcoma"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Inoperable and/or advanced osteosarcoma",
            "criterions": [
                {
                    "exact_snippets": "Inoperable",
                    "criterion": "operability",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "inoperable"
                        }
                    ]
                },
                {
                    "exact_snippets": "advanced osteosarcoma",
                    "criterion": "osteosarcoma stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "advanced"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Inoperable and/or advanced colorectal cancer, patients assessed as positive for NY-ESO-1 or MAGE-A3 expression at baseline",
            "criterions": [
                {
                    "exact_snippets": "Inoperable and/or advanced colorectal cancer",
                    "criterion": "colorectal cancer",
                    "requirements": [
                        {
                            "requirement_type": "operability",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "stage",
                            "expected_value": "advanced"
                        }
                    ]
                },
                {
                    "exact_snippets": "positive for NY-ESO-1",
                    "criterion": "NY-ESO-1 expression",
                    "requirements": [
                        {
                            "requirement_type": "expression",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "positive for ... MAGE-A3 expression",
                    "criterion": "MAGE-A3 expression",
                    "requirements": [
                        {
                            "requirement_type": "expression",
                            "expected_value": "positive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Inoperable and/or advanced/metastatic sarcoma, patients assessed as positive for NY-ESO-1 or MAGE-A3 expression at baseline",
            "criterions": [
                {
                    "exact_snippets": "Inoperable and/or advanced/metastatic sarcoma",
                    "criterion": "sarcoma",
                    "requirements": [
                        {
                            "requirement_type": "operability",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "advanced",
                                "metastatic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "positive for NY-ESO-1",
                    "criterion": "NY-ESO-1 expression",
                    "requirements": [
                        {
                            "requirement_type": "expression",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "positive for ... MAGE-A3 expression",
                    "criterion": "MAGE-A3 expression",
                    "requirements": [
                        {
                            "requirement_type": "expression",
                            "expected_value": "positive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.",
            "criterions": [
                {
                    "exact_snippets": "Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.",
                    "criterion": "measurable disease",
                    "requirements": [
                        {
                            "requirement_type": "evaluation criteria",
                            "expected_value": "Response Evaluation Criteria in Solid Tumors (RECIST) 1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Tumor lesion which is deemed feasible for biopsy and injection",
            "criterions": [
                {
                    "exact_snippets": "Tumor lesion which is deemed feasible for biopsy",
                    "criterion": "tumor lesion",
                    "requirements": [
                        {
                            "requirement_type": "feasibility for biopsy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Tumor lesion which is deemed feasible for ... injection",
                    "criterion": "tumor lesion",
                    "requirements": [
                        {
                            "requirement_type": "feasibility for injection",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. ECOG/WHO performance status 0 to 1.",
            "criterions": [
                {
                    "exact_snippets": "ECOG/WHO performance status 0 to 1",
                    "criterion": "ECOG/WHO performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Acceptable liver and renal function, defined as:",
            "criterions": [
                {
                    "exact_snippets": "Acceptable liver ... function",
                    "criterion": "liver function",
                    "requirements": [
                        {
                            "requirement_type": "acceptability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Acceptable ... renal function",
                    "criterion": "renal function",
                    "requirements": [
                        {
                            "requirement_type": "acceptability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin ≤1.5 x upper limit of normal (ULN; does not include patients with Gilbert's Disease), and",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin ≤1.5 x upper limit of normal (ULN; does not include patients with Gilbert's Disease)",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 x ULN, and",
            "criterions": [
                {
                    "exact_snippets": "Aspartate aminotransferase (AST) ... ≤3.0 x ULN",
                    "criterion": "Aspartate aminotransferase (AST) level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3.0,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alanine aminotransferase (ALT) ≤3.0 x ULN",
                    "criterion": "alanine aminotransferase (ALT) level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3.0,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Serum creatinine ≤1.5 x ULN",
            "criterions": [
                {
                    "exact_snippets": "Serum creatinine ≤1.5 x ULN",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Acceptable hematological function, defined as:",
            "criterions": [
                {
                    "exact_snippets": "Acceptable hematological function",
                    "criterion": "hematological function",
                    "requirements": [
                        {
                            "requirement_type": "acceptability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin ≥9 g/dL, and",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin ≥9 g/dL",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Neutrophils ≥1.5 x 109/L, and",
            "criterions": [
                {
                    "exact_snippets": "Neutrophils ≥1.5 x 109/L",
                    "criterion": "neutrophils",
                    "requirements": [
                        {
                            "requirement_type": "count",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelet count ≥100 x 109/L Patients may be transfused to meet the hemoglobin entry criteria.",
            "criterions": [
                {
                    "exact_snippets": "Platelet count ≥100 x 109/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Acceptable coagulation status defined by international normalized ratio (INR) of blood clotting, prothrombin time and activated partial thromboplastin time within ≤1.5 x upper limit of normal.",
            "criterions": [
                {
                    "exact_snippets": "international normalized ratio (INR) of blood clotting ... within ≤1.5 x upper limit of normal",
                    "criterion": "INR of blood clotting",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 1.5,
                                        "unit": "x upper limit of normal"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "prothrombin time ... within ≤1.5 x upper limit of normal",
                    "criterion": "prothrombin time",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 1.5,
                                        "unit": "x upper limit of normal"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "activated partial thromboplastin time within ≤1.5 x upper limit of normal",
                    "criterion": "activated partial thromboplastin time",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 1.5,
                                        "unit": "x upper limit of normal"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Negative pregnancy test at screening in all women of childbearing potential (WOCBP). Such patients must agree to use a highly effective method of contraception (Appendix 1) during study intervention and for 3 months after the last virus treatment, 4 months after the last dose of pembrolizumab, and 12 months after CPO dosing. Male patients and male partners of female patients must also use barrier contraception, i.e., condom, for the time periods specified for WOCBP, plus a further 3 month period.",
            "criterions": [
                {
                    "exact_snippets": "Negative pregnancy test at screening in all women of childbearing potential (WOCBP)",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "Such patients must agree to use a highly effective method of contraception (Appendix 1) during study intervention and for 3 months after the last virus treatment, 4 months after the last dose of pembrolizumab, and 12 months after CPO dosing",
                    "criterion": "contraception use (WOCBP)",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Male patients and male partners of female patients must also use barrier contraception, i.e., condom, for the time periods specified for WOCBP, plus a further 3 month period",
                    "criterion": "barrier contraception use (male patients and male partners)",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Urine pregnancy tests should have a sensitivity of at least 25 mIU/mL for human chorionic gonadotropin (hCG). If the urine test is positive, it must be followed by a quantitative analysis of hCG concentration in blood.",
            "criterions": [
                {
                    "exact_snippets": "Urine pregnancy tests should have a sensitivity of at least 25 mIU/mL for human chorionic gonadotropin (hCG).",
                    "criterion": "urine pregnancy test sensitivity",
                    "requirements": [
                        {
                            "requirement_type": "sensitivity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 25,
                                "unit": "mIU/mL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "If the urine test is positive, it must be followed by a quantitative analysis of hCG concentration in blood.",
                    "criterion": "hCG concentration in blood",
                    "requirements": [
                        {
                            "requirement_type": "quantitative analysis",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Prior therapy with an immune CPI is allowed provided a 6-week washout period is observed for patients with prior programmed cell death (PD)1 or PDL1 treatment",
            "criterions": [
                {
                    "exact_snippets": "Prior therapy with an immune CPI is allowed",
                    "criterion": "prior therapy with an immune CPI",
                    "requirements": [
                        {
                            "requirement_type": "allowance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "6-week washout period is observed for patients with prior programmed cell death (PD)1 or PDL1 treatment",
                    "criterion": "washout period for prior PD1 or PDL1 treatment",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Receipt of any oncolytic virus treatment, or administration of a vaccine containing live virus within 4 weeks before Day 1.",
            "criterions": [
                {
                    "exact_snippets": "Receipt of any oncolytic virus treatment",
                    "criterion": "oncolytic virus treatment",
                    "requirements": [
                        {
                            "requirement_type": "receipt",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "administration of a vaccine containing live virus within 4 weeks before Day 1",
                    "criterion": "vaccine containing live virus",
                    "requirements": [
                        {
                            "requirement_type": "administration",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Use of significant immunosuppressive medication, including high dose corticosteroid (defined as the equivalent of >10 mg/day prednisone) within 4 weeks before Day 1. Inhaled or topical corticosteroid use is allowed.",
            "criterions": [
                {
                    "exact_snippets": "Use of significant immunosuppressive medication",
                    "criterion": "immunosuppressive medication use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "high dose corticosteroid (defined as the equivalent of >10 mg/day prednisone) within 4 weeks before Day 1",
                    "criterion": "high dose corticosteroid use",
                    "requirements": [
                        {
                            "requirement_type": "dosage",
                            "expected_value": {
                                "operator": ">",
                                "value": 10,
                                "unit": "mg/day prednisone"
                            }
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 4 weeks before Day 1"
                        }
                    ]
                },
                {
                    "exact_snippets": "Inhaled or topical corticosteroid use is allowed",
                    "criterion": "inhaled or topical corticosteroid use",
                    "requirements": [
                        {
                            "requirement_type": "allowance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Prior or concomitant radiotherapy within 4 weeks before Day 1.",
            "criterions": [
                {
                    "exact_snippets": "Prior or concomitant radiotherapy within 4 weeks before Day 1.",
                    "criterion": "radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Participation in a study with an investigational drug or device within 4 weeks prior to Day 1.",
            "criterions": [
                {
                    "exact_snippets": "Participation in a study with an investigational drug or device within 4 weeks prior to Day 1.",
                    "criterion": "participation in a study with an investigational drug or device",
                    "requirements": [
                        {
                            "requirement_type": "time since last participation",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Active bacterial, viral, or fungal infection that requires systemic therapy.",
            "criterions": [
                {
                    "exact_snippets": "Active bacterial, viral, or fungal infection",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "bacterial",
                                "viral",
                                "fungal"
                            ]
                        },
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "requires systemic therapy",
                    "criterion": "systemic therapy",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Active autoimmune disease that has required systemic treatment in the past two years.",
            "criterions": [
                {
                    "exact_snippets": "Active autoimmune disease",
                    "criterion": "autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "required systemic treatment in the past two years",
                    "criterion": "systemic treatment for autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "past two years"
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the patient, if included in this study.",
            "criterions": [
                {
                    "exact_snippets": "Concomitant disease or condition that could interfere with the conduct of the study",
                    "criterion": "concomitant disease or condition",
                    "requirements": [
                        {
                            "requirement_type": "interference with study conduct",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Concomitant disease or condition ... that would, in the opinion of the investigator, pose an unacceptable risk to the patient",
                    "criterion": "concomitant disease or condition",
                    "requirements": [
                        {
                            "requirement_type": "risk to patient",
                            "expected_value": "unacceptable"
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Any concomitant medical condition requiring receipt of a therapeutic anticoagulant that, in the opinion of the treating physician, cannot safely be withheld to allow for repeated injection of PeptiCRAd 1 and tumor biopsies.",
            "criterions": [
                {
                    "exact_snippets": "Any concomitant medical condition requiring receipt of a therapeutic anticoagulant",
                    "criterion": "concomitant medical condition requiring therapeutic anticoagulant",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "in the opinion of the treating physician, cannot safely be withheld",
                    "criterion": "therapeutic anticoagulant",
                    "requirements": [
                        {
                            "requirement_type": "withholdability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Known infection with human immunodeficiency virus, hepatitis B, or hepatitis C or active tuberculosis.",
            "criterions": [
                {
                    "exact_snippets": "Known infection with human immunodeficiency virus",
                    "criterion": "human immunodeficiency virus infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Known infection with ... hepatitis B",
                    "criterion": "hepatitis B infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Known infection with ... hepatitis C",
                    "criterion": "hepatitis C infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active tuberculosis",
                    "criterion": "tuberculosis",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Known active central nervous system metastases. Patients with leptomeningeal disease, carcinomatous meningitis, symptomatic brain metastases, or radiographic signs of CNS hemorrhage are excluded.",
            "criterions": [
                {
                    "exact_snippets": "Known active central nervous system metastases",
                    "criterion": "central nervous system metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients with leptomeningeal disease",
                    "criterion": "leptomeningeal disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "carcinomatous meningitis",
                    "criterion": "carcinomatous meningitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "symptomatic brain metastases",
                    "criterion": "symptomatic brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "radiographic signs of CNS hemorrhage",
                    "criterion": "CNS hemorrhage",
                    "requirements": [
                        {
                            "requirement_type": "radiographic signs",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Note: Participants with asymptomatic brain metastases (i.e. off corticosteroids and anticonvulsants for at least 7 days) are permitted.",
            "criterions": [
                {
                    "exact_snippets": "asymptomatic brain metastases",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "symptoms",
                            "expected_value": "asymptomatic"
                        }
                    ]
                },
                {
                    "exact_snippets": "off corticosteroids ... for at least 7 days",
                    "criterion": "corticosteroid use",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 7,
                                "unit": "days"
                            }
                        },
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "off ... anticonvulsants for at least 7 days",
                    "criterion": "anticonvulsant use",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 7,
                                "unit": "days"
                            }
                        },
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Any prior severe AE according to Common Terminology Criteria for Adverse Events (CTCAE), severe hypersensitivity reaction attributed to prior anti-PD1 or PDL1 therapy or components of the study intervention or has a history of any contraindication that, in the investigator's opinion, would contraindicate pembrolizumab administration such as:",
            "criterions": [
                {
                    "exact_snippets": "prior severe AE according to Common Terminology Criteria for Adverse Events (CTCAE)",
                    "criterion": "prior severe adverse event",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        },
                        {
                            "requirement_type": "standard",
                            "expected_value": "Common Terminology Criteria for Adverse Events (CTCAE)"
                        }
                    ]
                },
                {
                    "exact_snippets": "severe hypersensitivity reaction attributed to prior anti-PD1 or PDL1 therapy",
                    "criterion": "severe hypersensitivity reaction",
                    "requirements": [
                        {
                            "requirement_type": "attribution",
                            "expected_value": [
                                "prior anti-PD1 therapy",
                                "prior PDL1 therapy"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "severe hypersensitivity reaction attributed to ... components of the study intervention",
                    "criterion": "severe hypersensitivity reaction",
                    "requirements": [
                        {
                            "requirement_type": "attribution",
                            "expected_value": "components of the study intervention"
                        }
                    ]
                },
                {
                    "exact_snippets": "history of any contraindication that, in the investigator's opinion, would contraindicate pembrolizumab administration",
                    "criterion": "contraindication to pembrolizumab",
                    "requirements": [
                        {
                            "requirement_type": "opinion",
                            "expected_value": "investigator's opinion"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Resolution of side effect of prior anti-PD1 or PDL1 therapy to Grade 1",
            "criterions": [
                {
                    "exact_snippets": "Resolution of side effect of prior anti-PD1 or PDL1 therapy to Grade 1",
                    "criterion": "side effect of prior anti-PD1 or PDL1 therapy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "Grade 1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Grade 2 or higher pneumonitis",
            "criterions": [
                {
                    "exact_snippets": "Grade 2 or higher pneumonitis",
                    "criterion": "pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Grade 4 AST or ALT elevation",
            "criterions": [
                {
                    "exact_snippets": "Grade 4 AST",
                    "criterion": "AST elevation",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "Grade 4"
                        }
                    ]
                },
                {
                    "exact_snippets": "Grade 4 ... ALT elevation",
                    "criterion": "ALT elevation",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "Grade 4"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Grade 3 or higher colitis attributable to immunotherapy Note: in the absence of clinical symptoms of pancreatitis, elevations of amylase or lipase are not contraindications to therapy on this trial.",
            "criterions": [
                {
                    "exact_snippets": "Grade 3 or higher colitis attributable to immunotherapy",
                    "criterion": "colitis",
                    "requirements": [
                        {
                            "requirement_type": "grade",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "N/A"
                            }
                        },
                        {
                            "requirement_type": "attribution",
                            "expected_value": "immunotherapy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. History of or planned tissue / organ transplant.",
            "criterions": [
                {
                    "exact_snippets": "History of ... tissue / organ transplant",
                    "criterion": "tissue/organ transplant",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "planned tissue / organ transplant",
                    "criterion": "tissue/organ transplant",
                    "requirements": [
                        {
                            "requirement_type": "planned",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Females who are pregnant or breast feeding or expecting to conceive within the projected duration of the study starting with the screening visit or males expecting to father children within the projected duration of the study starting with the screening visit.",
            "criterions": [
                {
                    "exact_snippets": "Females who are pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breast feeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "expecting to conceive within the projected duration of the study",
                    "criterion": "expecting to conceive",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "males expecting to father children within the projected duration of the study",
                    "criterion": "expecting to father children",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Unwillingness or inability to comply with the study protocol for any reason.",
            "criterions": [
                {
                    "exact_snippets": "Unwillingness ... to comply with the study protocol",
                    "criterion": "willingness to comply with study protocol",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "inability to comply with the study protocol",
                    "criterion": "ability to comply with study protocol",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Admission to an institution by virtue of an order issued by the judicial or administrative authorities.",
            "criterions": [
                {
                    "exact_snippets": "Admission to an institution by virtue of an order issued by the judicial or administrative authorities",
                    "criterion": "admission to an institution",
                    "requirements": [
                        {
                            "requirement_type": "cause",
                            "expected_value": "order issued by the judicial or administrative authorities"
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Sponsor or Contract Research Organization employees, or employees under the direct supervision of the investigator or the investigational sites and/or involved directly in the study.",
            "criterions": [
                {
                    "exact_snippets": "Sponsor or Contract Research Organization employees",
                    "criterion": "employment",
                    "requirements": [
                        {
                            "requirement_type": "affiliation",
                            "expected_value": [
                                "Sponsor",
                                "Contract Research Organization"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "employees under the direct supervision of the investigator",
                    "criterion": "employment",
                    "requirements": [
                        {
                            "requirement_type": "supervision",
                            "expected_value": "direct supervision of the investigator"
                        }
                    ]
                },
                {
                    "exact_snippets": "employees under the direct supervision of ... the investigational sites",
                    "criterion": "employment",
                    "requirements": [
                        {
                            "requirement_type": "supervision",
                            "expected_value": "direct supervision of the investigational sites"
                        }
                    ]
                },
                {
                    "exact_snippets": "employees ... involved directly in the study",
                    "criterion": "employment",
                    "requirements": [
                        {
                            "requirement_type": "involvement",
                            "expected_value": "directly in the study"
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Prior or concurrent malignancy, unless the natural history or treatment of the disease does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen.",
            "criterions": [
                {
                    "exact_snippets": "Prior or concurrent malignancy",
                    "criterion": "malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}