{
    "info": {
        "nct_id": "NCT06011772",
        "official_title": "A Phase 0 Study of EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer",
        "inclusion_criteria": "* Histologically or cytologically confirmed metastatic adenocarcinoma of colon or rectum that cannot be removed by surgery without prior systemic therapy for advanced disease (prior adjuvant chemotherapy completed >12 months from diagnosis of metastatic or advanced disease is allowed) for cohorts A and C and with one prior line of therapy but no more than 2 prior lines of therapy for advanced disease (prior adjuvant chemotherapy completed <12 months from diagnosis of metastatic or advanced disease is considered one line of therapy).\n\n  * Cohort A: May have received 1 cycle of chemotherapy± appropriate biologic agent pending results of RAS and BRAF. If results determine patient is eligible, the patient will be enrolled and will receive the addition of CIMAvax + Bevacizumab or CIMAvax+ anti-EGFR therapy in their second cycle.\n  * Cohort B: Patients with RAS- and BRAF wild-type metastatic CRC who have received at least one but no more than 2 prior therapies for advanced disease\n  * Cohort C: Patients with RAS- and BRAF wild-type metastatic CRC who have not received prior therapy for advanced disease and are candidates for metastatic disease resistant resection (one cycle of standard chemotherapy with or without appropriate biologic agent is allowed)\n* KRAS/NRAS/BRAF wild-type.\n* Have an ECOG Performance Status of 0-2\n* Patients must have adequate organ and marrow function as defined below:\n\n  * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L\n  * Platelets ≥ 75 x 10^9/L\n  * Hemoglobin ≥ 8 g/dL\n  * Creatinine clearance> 60 mL/min (Cockcroft-Gault Equation)\n  * ALT and AST ≤ 3 x ULN (ALT and AST ≤ 5 x ULN is acceptable if liver metastases are present\n  * Total bilirubin ≤ 1.5x ULN. For patients with well documented Gilbert's syndrome, total bilirubin ≤ 3x ULN with direct bilirubin within normal range\n* Have measurable disease per RECIST 1.1 criteria present.\n* Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.\n* Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.\n* Participant agrees to provide paired-tumor biopsy tissue while on study (cohort A and B) or allow tissue to be taken during surgery (cohort C)\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Toxicity ≥Grade 2 from prior chemotherapy with exception to Grade 2 peripheral neuropathy..\n* Other cancer requiring active treatment.\n* Prior exposure to anti-EGFR monoclonal antibody (i.e. cetuximab or panitumumab) for colorectal cancer treatment is exclusionary to Cohort A and C only\n* Participants with Her2 positive mutational status\n* Had major surgery within 4 weeks prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered major surgery) resulting from a prior surgery.\n* Has known immunosuppressive disease (e.g. HIV, AIDS or other immune depressing disease). Testing is not mandatory.\n* Participants with known active brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.\n* Active, clinically serious infections or other serious uncontrolled medical conditions or psychiatric illness/social situations that would limit compliance with study requirements.\n* 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, including, but not limited to:\n\n  * Myocardial infarction or arterial thromboembolic events within 6 months prior to baseline or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease\n  * History of documented congestive heart failure (New York Heart Association functional classification III or IV) within 6 months prior to baseline\n  * Uncontrolled hypertension (SBP>160/DBP>100 despite medical intervention).\n  * History of myocarditis of any etiology\n  * History of ventricular arrhythmias\n* Active major or clinically significant bleeding based on the International Society on Thrombosis and Hemostasis definition.\n* Pregnant or nursing female participants.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Histologically or cytologically confirmed metastatic adenocarcinoma of colon or rectum that cannot be removed by surgery without prior systemic therapy for advanced disease (prior adjuvant chemotherapy completed >12 months from diagnosis of metastatic or advanced disease is allowed) for cohorts A and C and with one prior line of therapy but no more than 2 prior lines of therapy for advanced disease (prior adjuvant chemotherapy completed <12 months from diagnosis of metastatic or advanced disease is considered one line of therapy).",
            "criterions": [
                {
                    "exact_snippets": "Histologically or cytologically confirmed metastatic adenocarcinoma of colon or rectum",
                    "criterion": "metastatic adenocarcinoma of colon or rectum",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "cannot be removed by surgery",
                    "criterion": "surgical removal",
                    "requirements": [
                        {
                            "requirement_type": "possibility",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "without prior systemic therapy for advanced disease",
                    "criterion": "prior systemic therapy for advanced disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "prior adjuvant chemotherapy completed >12 months from diagnosis of metastatic or advanced disease is allowed",
                    "criterion": "prior adjuvant chemotherapy completion time",
                    "requirements": [
                        {
                            "requirement_type": "time since diagnosis",
                            "expected_value": {
                                "operator": ">",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "with one prior line of therapy but no more than 2 prior lines of therapy for advanced disease",
                    "criterion": "prior lines of therapy for advanced disease",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 1,
                                        "unit": "lines"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "lines"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "prior adjuvant chemotherapy completed <12 months from diagnosis of metastatic or advanced disease is considered one line of therapy",
                    "criterion": "prior adjuvant chemotherapy completion time",
                    "requirements": [
                        {
                            "requirement_type": "time since diagnosis",
                            "expected_value": {
                                "operator": "<",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Cohort A: May have received 1 cycle of chemotherapy± appropriate biologic agent pending results of RAS and BRAF. If results determine patient is eligible, the patient will be enrolled and will receive the addition of CIMAvax + Bevacizumab or CIMAvax+ anti-EGFR therapy in their second cycle.",
            "criterions": [
                {
                    "exact_snippets": "May have received 1 cycle of chemotherapy",
                    "criterion": "chemotherapy cycles received",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "=",
                                "value": 1,
                                "unit": "cycle"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "pending results of RAS and BRAF",
                    "criterion": "RAS and BRAF results",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Cohort B: Patients with RAS- and BRAF wild-type metastatic CRC who have received at least one but no more than 2 prior therapies for advanced disease",
            "criterions": [
                {
                    "exact_snippets": "RAS- and BRAF wild-type metastatic CRC",
                    "criterion": "RAS mutation status",
                    "requirements": [
                        {
                            "requirement_type": "mutation status",
                            "expected_value": "wild-type"
                        }
                    ]
                },
                {
                    "exact_snippets": "RAS- and BRAF wild-type metastatic CRC",
                    "criterion": "BRAF mutation status",
                    "requirements": [
                        {
                            "requirement_type": "mutation status",
                            "expected_value": "wild-type"
                        }
                    ]
                },
                {
                    "exact_snippets": "metastatic CRC",
                    "criterion": "metastatic CRC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "at least one but no more than 2 prior therapies for advanced disease",
                    "criterion": "prior therapies for advanced disease",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 1,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Cohort C: Patients with RAS- and BRAF wild-type metastatic CRC who have not received prior therapy for advanced disease and are candidates for metastatic disease resistant resection (one cycle of standard chemotherapy with or without appropriate biologic agent is allowed)",
            "criterions": [
                {
                    "exact_snippets": "RAS- and BRAF wild-type metastatic CRC",
                    "criterion": "RAS and BRAF mutation status",
                    "requirements": [
                        {
                            "requirement_type": "mutation status",
                            "expected_value": [
                                "wild-type"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "metastatic CRC",
                    "criterion": "metastatic colorectal cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "have not received prior therapy for advanced disease",
                    "criterion": "prior therapy for advanced disease",
                    "requirements": [
                        {
                            "requirement_type": "prior therapy",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "candidates for metastatic disease resistant resection",
                    "criterion": "candidate for metastatic disease resistant resection",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* KRAS/NRAS/BRAF wild-type.",
            "criterions": [
                {
                    "exact_snippets": "KRAS/NRAS/BRAF wild-type",
                    "criterion": "KRAS gene",
                    "requirements": [
                        {
                            "requirement_type": "mutation status",
                            "expected_value": "wild-type"
                        }
                    ]
                },
                {
                    "exact_snippets": "KRAS/NRAS/BRAF wild-type",
                    "criterion": "NRAS gene",
                    "requirements": [
                        {
                            "requirement_type": "mutation status",
                            "expected_value": "wild-type"
                        }
                    ]
                },
                {
                    "exact_snippets": "KRAS/NRAS/BRAF wild-type",
                    "criterion": "BRAF gene",
                    "requirements": [
                        {
                            "requirement_type": "mutation status",
                            "expected_value": "wild-type"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have an ECOG Performance Status of 0-2",
            "criterions": [
                {
                    "exact_snippets": "ECOG Performance Status of 0-2",
                    "criterion": "ECOG Performance Status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have adequate organ and marrow function as defined below:",
            "criterions": [
                {
                    "exact_snippets": "adequate organ and marrow function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "adequate organ and marrow function",
                    "criterion": "marrow function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count (ANC) ≥ 1.5 x 109/L",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count (ANC) ≥ 1.5 x 109/L",
                    "criterion": "absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelets ≥ 75 x 10^9/L",
            "criterions": [
                {
                    "exact_snippets": "Platelets ≥ 75 x 10^9/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 75,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin ≥ 8 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin ≥ 8 g/dL",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 8,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Creatinine clearance> 60 mL/min (Cockcroft-Gault Equation)",
            "criterions": [
                {
                    "exact_snippets": "Creatinine clearance> 60 mL/min",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 60,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ALT and AST ≤ 3 x ULN (ALT and AST ≤ 5 x ULN is acceptable if liver metastases are present",
            "criterions": [
                {
                    "exact_snippets": "ALT and AST ≤ 3 x ULN",
                    "criterion": "ALT and AST levels",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ALT and AST ≤ 5 x ULN ... if liver metastases are present",
                    "criterion": "ALT and AST levels with liver metastases",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "condition",
                            "expected_value": "liver metastases"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin ≤ 1.5x ULN. For patients with well documented Gilbert's syndrome, total bilirubin ≤ 3x ULN with direct bilirubin within normal range",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin ≤ 1.5x ULN",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with well documented Gilbert's syndrome, total bilirubin ≤ 3x ULN",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with well documented Gilbert's syndrome ... direct bilirubin within normal range",
                    "criterion": "direct bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": "within normal range"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have measurable disease per RECIST 1.1 criteria present.",
            "criterions": [
                {
                    "exact_snippets": "measurable disease per RECIST 1.1 criteria present",
                    "criterion": "measurable disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "criteria",
                            "expected_value": "RECIST 1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.",
            "criterions": [
                {
                    "exact_snippets": "Participants of child-bearing potential",
                    "criterion": "child-bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must agree to use adequate contraceptive methods",
                    "criterion": "use of contraceptive methods",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Should a woman become pregnant or suspect she is pregnant",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.",
            "criterions": [
                {
                    "exact_snippets": "Participant must understand the investigational nature of this study",
                    "criterion": "understanding of study nature",
                    "requirements": [
                        {
                            "requirement_type": "understanding",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participant agrees to provide paired-tumor biopsy tissue while on study (cohort A and B) or allow tissue to be taken during surgery (cohort C)",
            "criterions": [
                {
                    "exact_snippets": "Participant agrees to provide paired-tumor biopsy tissue while on study (cohort A and B)",
                    "criterion": "paired-tumor biopsy tissue",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "provision",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "allow tissue to be taken during surgery (cohort C)",
                    "criterion": "tissue",
                    "requirements": [
                        {
                            "requirement_type": "allowance",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "provision",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "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": "* Toxicity ≥Grade 2 from prior chemotherapy with exception to Grade 2 peripheral neuropathy..",
            "criterions": [
                {
                    "exact_snippets": "Toxicity ≥Grade 2 from prior chemotherapy",
                    "criterion": "toxicity from prior chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "exception to Grade 2 peripheral neuropathy",
                    "criterion": "peripheral neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "=",
                                "value": 2,
                                "unit": "Grade"
                            }
                        },
                        {
                            "requirement_type": "exception",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Other cancer requiring active treatment.",
            "criterions": [
                {
                    "exact_snippets": "Other cancer requiring active treatment.",
                    "criterion": "other cancer",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "active treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior exposure to anti-EGFR monoclonal antibody (i.e. cetuximab or panitumumab) for colorectal cancer treatment is exclusionary to Cohort A and C only",
            "criterions": [
                {
                    "exact_snippets": "Prior exposure to anti-EGFR monoclonal antibody (i.e. cetuximab or panitumumab)",
                    "criterion": "prior exposure to anti-EGFR monoclonal antibody",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "colorectal cancer treatment",
                    "criterion": "colorectal cancer treatment",
                    "requirements": [
                        {
                            "requirement_type": "purpose",
                            "expected_value": "treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants with Her2 positive mutational status",
            "criterions": [
                {
                    "exact_snippets": "Her2 positive mutational status",
                    "criterion": "Her2 mutational status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "positive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Had major surgery within 4 weeks prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered major surgery) resulting from a prior surgery.",
            "criterions": [
                {
                    "exact_snippets": "Had major surgery within 4 weeks prior to starting study drug",
                    "criterion": "major surgery",
                    "requirements": [
                        {
                            "requirement_type": "time since surgery",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "has not recovered from major side effects ... resulting from a prior surgery",
                    "criterion": "recovery from major side effects",
                    "requirements": [
                        {
                            "requirement_type": "recovery status",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has known immunosuppressive disease (e.g. HIV, AIDS or other immune depressing disease). Testing is not mandatory.",
            "criterions": [
                {
                    "exact_snippets": "Has known immunosuppressive disease (e.g. HIV, AIDS or other immune depressing disease)",
                    "criterion": "immunosuppressive disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Testing is not mandatory",
                    "criterion": "immunosuppressive disease testing",
                    "requirements": [
                        {
                            "requirement_type": "mandatory",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants with known active brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.",
            "criterions": [
                {
                    "exact_snippets": "known active brain metastases",
                    "criterion": "active brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active, clinically serious infections or other serious uncontrolled medical conditions or psychiatric illness/social situations that would limit compliance with study requirements.",
            "criterions": [
                {
                    "exact_snippets": "Active, clinically serious infections",
                    "criterion": "infections",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "clinically serious"
                        },
                        {
                            "requirement_type": "activity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "serious uncontrolled medical conditions",
                    "criterion": "medical conditions",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": "serious"
                        }
                    ]
                },
                {
                    "exact_snippets": "psychiatric illness/social situations that would limit compliance with study requirements",
                    "criterion": "psychiatric illness/social situations",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance",
                            "expected_value": "limit compliance with study requirements"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 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, including, but not limited to:",
            "criterions": [
                {
                    "exact_snippets": "History or current evidence of any condition",
                    "criterion": "condition",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "therapy",
                    "criterion": "therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "laboratory abnormality",
                    "criterion": "laboratory abnormality",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Myocardial infarction or arterial thromboembolic events within 6 months prior to baseline or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease",
            "criterions": [
                {
                    "exact_snippets": "Myocardial infarction ... within 6 months prior to baseline",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "arterial thromboembolic events within 6 months prior to baseline",
                    "criterion": "arterial thromboembolic events",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "severe or unstable angina",
                    "criterion": "angina",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "severe",
                                "unstable"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "New York Heart Association (NYHA) Class III or IV disease",
                    "criterion": "NYHA class",
                    "requirements": [
                        {
                            "requirement_type": "classification",
                            "expected_value": [
                                "Class III",
                                "Class IV"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of documented congestive heart failure (New York Heart Association functional classification III or IV) within 6 months prior to baseline",
            "criterions": [
                {
                    "exact_snippets": "History of documented congestive heart failure (New York Heart Association functional classification III or IV)",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "New York Heart Association functional classification III",
                                "New York Heart Association functional classification IV"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "within 6 months prior to baseline",
                    "criterion": "time since congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "time since occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled hypertension (SBP>160/DBP>100 despite medical intervention).",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled hypertension",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "SBP>160",
                    "criterion": "systolic blood pressure (SBP)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 160,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "DBP>100",
                    "criterion": "diastolic blood pressure (DBP)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 100,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "despite medical intervention",
                    "criterion": "response to medical intervention",
                    "requirements": [
                        {
                            "requirement_type": "effectiveness",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of myocarditis of any etiology",
            "criterions": [
                {
                    "exact_snippets": "History of myocarditis",
                    "criterion": "myocarditis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of ventricular arrhythmias",
            "criterions": [
                {
                    "exact_snippets": "History of ventricular arrhythmias",
                    "criterion": "ventricular arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active major or clinically significant bleeding based on the International Society on Thrombosis and Hemostasis definition.",
            "criterions": [
                {
                    "exact_snippets": "Active major or clinically significant bleeding",
                    "criterion": "bleeding",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "active major",
                                "clinically significant"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "based on the International Society on Thrombosis and Hemostasis definition",
                    "criterion": "bleeding definition",
                    "requirements": [
                        {
                            "requirement_type": "source",
                            "expected_value": "International Society on Thrombosis and Hemostasis"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant or nursing female participants.",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "nursing female participants",
                    "criterion": "nursing",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}