{
    "info": {
        "nct_id": "NCT02094573",
        "official_title": "A Randomized Phase 2 Study of AP26113 in Patients With ALK-positive, Non-small Cell Lung Cancer (NSCLC) Previously Treated With Crizotinib",
        "inclusion_criteria": "1. Have histologically or cytologically confirmed locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) that is anaplastic lymphoma kinase (ALK+).\n2. Must meet one of the following two criteria:\n\n   1. Have documented ALK rearrangement by a positive result from the Vysis® ALK Break-Apart fluorescence in situ hybridization (FISH) Probe Kit; or\n   2. Have documented ALK positivity by a different test and tissue available for the Vysis® FISH test. Tissue should be derived preferably from a biopsy taken after progression with crizotinib. If such a sample is not available, testing may be performed with archived tumor tissue.\n3. Had progressive disease while on crizotinib, as assessed by the investigator or treating physician.\n4. Have at least 1 measurable lesion per RECIST v1.1. Note: Previously irradiated lesions may not be used for target lesions, unless there is unambiguous radiological progression after radiotherapy. Brain lesions may not be used as target lesions if they were: 1) previously treated with whole brain radiation therapy (WBRT) within 3 months, or 2) previously treated by stereotactic radiosurgery (SRS) or surgical resection.\n5. Recovered from toxicities related to prior anticancer therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, v4.0) grade ≤2.\n6. Are a male or female participants ≥18 years old.\n7. Have a life expectancy ≥3 months.\n8. Have adequate organ and hematologic function, as determined by:\n\n   1. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN; ≤5 x ULN is acceptable if liver metastases are present)\n   2. Total serum bilirubin ≤1.5 x ULN (<3.0 x ULN for participants with Gilbert syndrome)\n   3. Serum creatinine ≤1.5 x ULN\n   4. Serum lipase/amylase ≤1.5 x ULN\n   5. Absolute neutrophil count (ANC) ≥1500/µL\n   6. Platelets ≥75000/µL\n   7. Hemoglobin ≥10 g/dL\n9. Have Eastern Cooperative Oncology Group (ECOG) performance status ≤2.\n10. Have normal QT interval on screening electrocardiogram (ECG) evaluation, defined as QT interval corrected (Fridericia) (QTcF) of ≤450 ms in males or ≤470 ms in females.\n11. For female participants of childbearing potential, a negative pregnancy test must be documented prior to enrollment.\n12. Female and male participants who are fertile must agree to use a highly effective form of contraception with their sexual partners throughout study participation.\n13. Must provide a signed and dated informed consent indicating that the participants has been informed of all pertinent aspects of the study, including the potential risks, and is willingly participating.\n14. Have the willingness and ability to comply with scheduled visits and study procedures.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Received any prior ALK-targeted TKI other than crizotinib.\n2. Received crizotinib within 3 days of the first dose of brigatinib (Day 1, Cycle 1).\n3. Received cytotoxic chemotherapy, investigational agents, or radiation within 14 days, except SRS or stereotactic body radiosurgery.\n4. Received monoclonal antibodies or had major surgery within 30 days of the first dose of brigatinib (Day 1, Cycle 1).\n5. Have been diagnosed with another primary malignancy within the past 3 years (except for adequately treated non-melanoma skin cancer, cervical cancer in situ, or prostate cancer, which are allowed within 3 years).\n6. Have symptomatic CNS metastases that are neurologically unstable or require an increasing dose of corticosteroids.\n7. Have current spinal cord compression.\n8. Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:\n\n   1. Myocardial infarction (MI) within 6 months prior to the first dose of brigatinib\n   2. Unstable angina within 6 months prior to first dose\n   3. Congestive heart failure (CHF) within 6 months prior to first dose\n   4. History of clinically significant (as determined by the treating physician) atrial arrhythmia\n   5. Any history of ventricular arrhythmia\n   6. Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose\n9. Have a history or the presence of pulmonary interstitial disease or drug-related pneumonitis.\n10. Have an ongoing or active infection. The requirement for intravenous (IV) antibiotics is considered active infection.\n11. Have a known history of human immunodeficiency virus (HIV). Testing is not required in the absence of history.\n12. Have a history of or active significant gastrointestinal (GI) bleeding within 3 months of the first dose of brigatinib.\n13. Have a known or suspected hypersensitivity to brigatinib or its excipients.\n14. Have malabsorption syndrome or other GI illness that could affect oral absorption of the study drug.\n15. Have any condition or illness that, in the opinion of the investigator, would compromise participants safety or interfere with evaluation of the drug study.\n16. Be pregnant or breastfeeding.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Have histologically or cytologically confirmed locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) that is anaplastic lymphoma kinase (ALK+).",
            "criterions": [
                {
                    "exact_snippets": "histologically or cytologically confirmed",
                    "criterion": "confirmation method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC)",
                    "criterion": "Non-small Cell Lung Cancer (NSCLC)",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "locally advanced",
                                "metastatic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "anaplastic lymphoma kinase (ALK+)",
                    "criterion": "anaplastic lymphoma kinase (ALK)",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "positive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Must meet one of the following two criteria:",
            "criterions": [
                {
                    "exact_snippets": "Must meet one of the following two criteria",
                    "criterion": "eligibility criteria",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": ">= 1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Have documented ALK rearrangement by a positive result from the Vysis® ALK Break-Apart fluorescence in situ hybridization (FISH) Probe Kit; or",
            "criterions": [
                {
                    "exact_snippets": "documented ALK rearrangement by a positive result from the Vysis® ALK Break-Apart fluorescence in situ hybridization (FISH) Probe Kit",
                    "criterion": "ALK rearrangement",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "test",
                            "expected_value": "positive result from the Vysis® ALK Break-Apart fluorescence in situ hybridization (FISH) Probe Kit"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Have documented ALK positivity by a different test and tissue available for the Vysis® FISH test. Tissue should be derived preferably from a biopsy taken after progression with crizotinib. If such a sample is not available, testing may be performed with archived tumor tissue.",
            "criterions": [
                {
                    "exact_snippets": "documented ALK positivity by a different test",
                    "criterion": "ALK positivity",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "tissue available for the Vysis® FISH test",
                    "criterion": "tissue availability for Vysis® FISH test",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Tissue should be derived preferably from a biopsy taken after progression with crizotinib",
                    "criterion": "tissue derivation from biopsy after progression with crizotinib",
                    "requirements": [
                        {
                            "requirement_type": "preference",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "If such a sample is not available, testing may be performed with archived tumor tissue",
                    "criterion": "archived tumor tissue",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Had progressive disease while on crizotinib, as assessed by the investigator or treating physician.",
            "criterions": [
                {
                    "exact_snippets": "progressive disease while on crizotinib",
                    "criterion": "progressive disease on crizotinib",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "as assessed by the investigator or treating physician",
                    "criterion": "assessment by investigator or treating physician",
                    "requirements": [
                        {
                            "requirement_type": "assessor",
                            "expected_value": [
                                "investigator",
                                "treating physician"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Have at least 1 measurable lesion per RECIST v1.1. Note: Previously irradiated lesions may not be used for target lesions, unless there is unambiguous radiological progression after radiotherapy. Brain lesions may not be used as target lesions if they were: 1) previously treated with whole brain radiation therapy (WBRT) within 3 months, or 2) previously treated by stereotactic radiosurgery (SRS) or surgical resection.",
            "criterions": [
                {
                    "exact_snippets": "at least 1 measurable lesion per RECIST v1.1",
                    "criterion": "measurable lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Previously irradiated lesions may not be used for target lesions, unless there is unambiguous radiological progression after radiotherapy",
                    "criterion": "previously irradiated lesions",
                    "requirements": [
                        {
                            "requirement_type": "use as target lesions",
                            "expected_value": "unambiguous radiological progression after radiotherapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "Brain lesions may not be used as target lesions if they were: 1) previously treated with whole brain radiation therapy (WBRT) within 3 months",
                    "criterion": "brain lesions previously treated with WBRT",
                    "requirements": [
                        {
                            "requirement_type": "use as target lesions",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Brain lesions may not be used as target lesions if they were: ... 2) previously treated by stereotactic radiosurgery (SRS) or surgical resection",
                    "criterion": "brain lesions previously treated by SRS or surgical resection",
                    "requirements": [
                        {
                            "requirement_type": "use as target lesions",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Recovered from toxicities related to prior anticancer therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, v4.0) grade ≤2.",
            "criterions": [
                {
                    "exact_snippets": "Recovered from toxicities related to prior anticancer therapy",
                    "criterion": "recovery from prior therapy toxicities",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "NCI CTCAE grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Are a male or female participants ≥18 years old.",
            "criterions": [
                {
                    "exact_snippets": "male or female participants",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "≥18 years old",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Have a life expectancy ≥3 months.",
            "criterions": [
                {
                    "exact_snippets": "life expectancy ≥3 months",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Have adequate organ and hematologic function, as determined by:",
            "criterions": [
                {
                    "exact_snippets": "adequate organ and hematologic function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "adequate organ and hematologic function",
                    "criterion": "hematologic function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN; ≤5 x ULN is acceptable if liver metastases are present)",
            "criterions": [
                {
                    "exact_snippets": "Alanine aminotransferase (ALT) ... ≤2.5 x upper limit of normal (ULN; ≤5 x ULN is acceptable if liver metastases are present)",
                    "criterion": "Alanine aminotransferase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2.5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN; ≤5 x ULN is acceptable if liver metastases are present)",
                    "criterion": "aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2.5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "liver metastases ... ≤5 x ULN is acceptable",
                    "criterion": "liver metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Total serum bilirubin ≤1.5 x ULN (<3.0 x ULN for participants with Gilbert syndrome)",
            "criterions": [
                {
                    "exact_snippets": "Total serum bilirubin ≤1.5 x ULN",
                    "criterion": "total serum bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "<3.0 x ULN for participants with Gilbert syndrome",
                    "criterion": "total serum bilirubin for participants with Gilbert syndrome",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 3.0,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. 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": "4. Serum lipase/amylase ≤1.5 x ULN",
            "criterions": [
                {
                    "exact_snippets": "Serum lipase/amylase ≤1.5 x ULN",
                    "criterion": "serum lipase/amylase",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Absolute neutrophil count (ANC) ≥1500/µL",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count (ANC) ≥1500/µL",
                    "criterion": "absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1500,
                                "unit": "µL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Platelets ≥75000/µL",
            "criterions": [
                {
                    "exact_snippets": "Platelets ≥75000/µL",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 75000,
                                "unit": "/µL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Hemoglobin ≥10 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin ≥10 g/dL",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 10,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Have Eastern Cooperative Oncology Group (ECOG) performance status ≤2.",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status ≤2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Have normal QT interval on screening electrocardiogram (ECG) evaluation, defined as QT interval corrected (Fridericia) (QTcF) of ≤450 ms in males or ≤470 ms in females.",
            "criterions": [
                {
                    "exact_snippets": "normal QT interval on screening electrocardiogram (ECG) evaluation",
                    "criterion": "QT interval",
                    "requirements": [
                        {
                            "requirement_type": "normality",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "QT interval corrected (Fridericia) (QTcF) of ≤450 ms in males",
                    "criterion": "QTcF in males",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 450,
                                "unit": "ms"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "QT interval corrected (Fridericia) (QTcF) of ... ≤470 ms in females",
                    "criterion": "QTcF in females",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 470,
                                "unit": "ms"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. For female participants of childbearing potential, a negative pregnancy test must be documented prior to enrollment.",
            "criterions": [
                {
                    "exact_snippets": "female participants of childbearing potential",
                    "criterion": "female participants of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "a negative pregnancy test must be documented",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Female and male participants who are fertile must agree to use a highly effective form of contraception with their sexual partners throughout study participation.",
            "criterions": [
                {
                    "exact_snippets": "Female and male participants who are fertile",
                    "criterion": "fertility",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must agree to use a highly effective form of contraception",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Must provide a signed and dated informed consent indicating that the participants has been informed of all pertinent aspects of the study, including the potential risks, and is willingly participating.",
            "criterions": [
                {
                    "exact_snippets": "Must provide a signed and dated informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "dated",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "indicating that the participants has been informed of all pertinent aspects of the study, including the potential risks",
                    "criterion": "participant information",
                    "requirements": [
                        {
                            "requirement_type": "informed",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "is willingly participating",
                    "criterion": "willing participation",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Have the willingness and ability to comply with scheduled visits and study procedures.",
            "criterions": [
                {
                    "exact_snippets": "willingness and ability to comply with scheduled visits and study procedures",
                    "criterion": "compliance with study protocol",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "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": "1. Received any prior ALK-targeted TKI other than crizotinib.",
            "criterions": [
                {
                    "exact_snippets": "Received any prior ALK-targeted TKI other than crizotinib",
                    "criterion": "prior ALK-targeted TKI",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": "crizotinib"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Received crizotinib within 3 days of the first dose of brigatinib (Day 1, Cycle 1).",
            "criterions": [
                {
                    "exact_snippets": "Received crizotinib within 3 days of the first dose of brigatinib",
                    "criterion": "crizotinib administration",
                    "requirements": [
                        {
                            "requirement_type": "time since last dose",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Received cytotoxic chemotherapy, investigational agents, or radiation within 14 days, except SRS or stereotactic body radiosurgery.",
            "criterions": [
                {
                    "exact_snippets": "Received cytotoxic chemotherapy ... within 14 days",
                    "criterion": "cytotoxic chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Received ... investigational agents ... within 14 days",
                    "criterion": "investigational agents",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Received ... radiation within 14 days",
                    "criterion": "radiation",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except SRS or stereotactic body radiosurgery",
                    "criterion": "SRS or stereotactic body radiosurgery",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Received monoclonal antibodies or had major surgery within 30 days of the first dose of brigatinib (Day 1, Cycle 1).",
            "criterions": [
                {
                    "exact_snippets": "Received monoclonal antibodies",
                    "criterion": "monoclonal antibodies",
                    "requirements": [
                        {
                            "requirement_type": "receipt",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "had major surgery within 30 days of the first dose of brigatinib",
                    "criterion": "major surgery",
                    "requirements": [
                        {
                            "requirement_type": "time since surgery",
                            "expected_value": {
                                "operator": "<=",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Have been diagnosed with another primary malignancy within the past 3 years (except for adequately treated non-melanoma skin cancer, cervical cancer in situ, or prostate cancer, which are allowed within 3 years).",
            "criterions": [
                {
                    "exact_snippets": "Have been diagnosed with another primary malignancy within the past 3 years",
                    "criterion": "diagnosis of another primary malignancy",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except for adequately treated non-melanoma skin cancer",
                    "criterion": "adequately treated non-melanoma skin cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "cervical cancer in situ",
                    "criterion": "cervical cancer in situ",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "prostate cancer, which are allowed within 3 years",
                    "criterion": "prostate cancer",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Have symptomatic CNS metastases that are neurologically unstable or require an increasing dose of corticosteroids.",
            "criterions": [
                {
                    "exact_snippets": "Have symptomatic CNS metastases",
                    "criterion": "CNS metastases",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "neurologically unstable",
                    "criterion": "neurological stability",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": "unstable"
                        }
                    ]
                },
                {
                    "exact_snippets": "require an increasing dose of corticosteroids",
                    "criterion": "corticosteroid dose",
                    "requirements": [
                        {
                            "requirement_type": "dose trend",
                            "expected_value": "increasing"
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Have current spinal cord compression.",
            "criterions": [
                {
                    "exact_snippets": "current spinal cord compression",
                    "criterion": "spinal cord compression",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:",
            "criterions": [
                {
                    "exact_snippets": "significant, uncontrolled, or active cardiovascular disease",
                    "criterion": "cardiovascular disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "activity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Myocardial infarction (MI) within 6 months prior to the first dose of brigatinib",
            "criterions": [
                {
                    "exact_snippets": "Myocardial infarction (MI) within 6 months prior to the first dose of brigatinib",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Unstable angina within 6 months prior to first dose",
            "criterions": [
                {
                    "exact_snippets": "Unstable angina within 6 months prior to first dose",
                    "criterion": "unstable angina",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Congestive heart failure (CHF) within 6 months prior to first dose",
            "criterions": [
                {
                    "exact_snippets": "Congestive heart failure (CHF) within 6 months prior to first dose",
                    "criterion": "congestive heart failure (CHF)",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 6 months prior to first dose"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. History of clinically significant (as determined by the treating physician) atrial arrhythmia",
            "criterions": [
                {
                    "exact_snippets": "History of clinically significant (as determined by the treating physician) atrial arrhythmia",
                    "criterion": "atrial arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "significance",
                            "expected_value": "clinically significant (as determined by the treating physician)"
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Any history of ventricular arrhythmia",
            "criterions": [
                {
                    "exact_snippets": "history of ventricular arrhythmia",
                    "criterion": "ventricular arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose",
            "criterions": [
                {
                    "exact_snippets": "Cerebrovascular accident ... within 6 months prior to first dose",
                    "criterion": "cerebrovascular accident",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "transient ischemic attack within 6 months prior to first dose",
                    "criterion": "transient ischemic attack",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Have a history or the presence of pulmonary interstitial disease or drug-related pneumonitis.",
            "criterions": [
                {
                    "exact_snippets": "history or the presence of pulmonary interstitial disease",
                    "criterion": "pulmonary interstitial disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history or the presence of ... drug-related pneumonitis",
                    "criterion": "drug-related pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Have an ongoing or active infection. The requirement for intravenous (IV) antibiotics is considered active infection.",
            "criterions": [
                {
                    "exact_snippets": "Have an ongoing or active infection",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "ongoing or active"
                        }
                    ]
                },
                {
                    "exact_snippets": "requirement for intravenous (IV) antibiotics is considered active infection",
                    "criterion": "intravenous (IV) antibiotics",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Have a known history of human immunodeficiency virus (HIV). Testing is not required in the absence of history.",
            "criterions": [
                {
                    "exact_snippets": "known history of human immunodeficiency virus (HIV)",
                    "criterion": "human immunodeficiency virus (HIV)",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Have a history of or active significant gastrointestinal (GI) bleeding within 3 months of the first dose of brigatinib.",
            "criterions": [
                {
                    "exact_snippets": "Have a history of or active significant gastrointestinal (GI) bleeding",
                    "criterion": "gastrointestinal (GI) bleeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "within 3 months of the first dose of brigatinib",
                    "criterion": "time since last significant GI bleeding",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Have a known or suspected hypersensitivity to brigatinib or its excipients.",
            "criterions": [
                {
                    "exact_snippets": "known or suspected hypersensitivity to brigatinib",
                    "criterion": "hypersensitivity to brigatinib",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity to ... excipients",
                    "criterion": "hypersensitivity to excipients",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Have malabsorption syndrome or other GI illness that could affect oral absorption of the study drug.",
            "criterions": [
                {
                    "exact_snippets": "malabsorption syndrome",
                    "criterion": "malabsorption syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "other GI illness that could affect oral absorption of the study drug",
                    "criterion": "GI illness affecting oral absorption",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Have any condition or illness that, in the opinion of the investigator, would compromise participants safety or interfere with evaluation of the drug study.",
            "criterions": [
                {
                    "exact_snippets": "Have any condition or illness that, in the opinion of the investigator, would compromise participants safety",
                    "criterion": "condition or illness",
                    "requirements": [
                        {
                            "requirement_type": "impact on safety",
                            "expected_value": "compromise participants safety"
                        }
                    ]
                },
                {
                    "exact_snippets": "Have any condition or illness that, in the opinion of the investigator, would ... interfere with evaluation of the drug study",
                    "criterion": "condition or illness",
                    "requirements": [
                        {
                            "requirement_type": "impact on study evaluation",
                            "expected_value": "interfere with evaluation of the drug study"
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Be pregnant or breastfeeding.",
            "criterions": [
                {
                    "exact_snippets": "Be pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "breastfeeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}