{
    "info": {
        "nct_id": "NCT05715229",
        "official_title": "A Multicenter Phase II Randomized Trial Of Immunotherapy Versus Chemotherapy Guided By Circulating Tumor DNA-Based Molecular Response On Patients With Metastatic NSCLC",
        "inclusion_criteria": "1. Eligible patients will have newly diagnosed, previously untreated histologically documented Stage IV NSCLC\n2. Eligible patients will be required to have positive PD-L1 expression ≥1% by IHC using Dako 22C3 assay.\n3. Patients will require a baseline Guardant360 CDx test prior to enrollment\n4. Patients willing to undergo serial ctDNA testing as required by protocol\n5. Patients will be over the age of 18\n6. Life expectancy ≥12 weeks\n7. Measurable (RECIST 1.1) indicator lesion not previously irradiated, with measurable disease determined per the treating investigator.\n8. Prior palliative radiotherapy to non-CNS lesions must have been completed at least 2 weeks prior to randomization\n9. ECOG Performance Score ≤2\n10. Adequate organ function\n11. Hemoglobin > 9 g/dL\n12. Platelets > 100,000mm3 or 100 x 109/L\n13. AST, ALT < 2.5 x ULN with no liver metastases or < 5x ULN with the presence of liver metastases\n14. Total bilirubin < 1.5 x ULN if no liver metastases or < 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases\n15. Absolute neutrophil count (ANC) > 1500 cells/mm3\n16. Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance ≥ 60ml/min calculated by Cockcroft and Gault's equation\n17. Willing to use highly effective contraceptive measures if child-bearing potential or if the patient's sexual partner is a woman of childbearing potential: a. Female subjects should be using a highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to starting of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: i. Post-menopausal is defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments ii. Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the the post-menopausal range for the institution iii. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not a tubal ligation b. Male subjects should be willing to use barrier contraception\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Patients under the age of 18\n2. Inability to provide informed consent by either the patient or the authorized representative\n3. Patients with known EGFR, ALK, ROS1, MET, and RET oncogenic driver alterations that have approved first-line targeted therapies are excluded from the study (All patients must have a tissue or blood-based testing to identify these driver alterations)\n4. Patients with no detectable ctDNA or ctDNA VAF ≤ 0.3% on Guardant360 CDx at baseline\n5. Subjects with untreated CNS metastases are excluded.\n6. Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to randomization. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization.\n7. Subjects with carcinomatous meningitis\n8. Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before randomization\n9. Subjects with previous malignancies (except non-melanoma skin cancers, and in situ cancers such as the following: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to randomization and no additional therapy is required or anticipated to be needed during the study period.\n10. Other active malignancy requiring concurrent intervention.\n11. Subjects with an active, known, or suspected autoimmune disease. Subjects with type I diabetes mellitus, and hypothyroidism only require hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.\n12. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroids > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.\n13. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.\n14. Significant uncontrolled cardiovascular disease, including but not limited to, any of the following:\n\n    1. Uncontrolled hypertension, which is defined as systolic blood pressure > 160 mm Hg or diastolic blood pressure > 100 mm Hg despite optimal medical management.\n    2. Active coronary artery disease, including unstable all newly diagnosed angina within 3 months of study enrollment.\n    3. Myocardial infarction in the past 6 months.\n    4. History of congenital long QT syndrome.\n    5. History of clinically significant arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or torsade de pointes.\n    6. Uncontrolled heart failure, defined as class III of 4 by the New York Heart Association functional classification.\n    7. History of a current diagnosis of myocarditis.\n15. the Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.\n16. Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection\n17. Subjects with Grade 2 peripheral neuropathy\n18. Life expectancy <12 weeks",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Eligible patients will have newly diagnosed, previously untreated histologically documented Stage IV NSCLC",
            "criterions": [
                {
                    "exact_snippets": "newly diagnosed",
                    "criterion": "diagnosis status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "newly diagnosed"
                        }
                    ]
                },
                {
                    "exact_snippets": "previously untreated",
                    "criterion": "treatment history",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "untreated"
                        }
                    ]
                },
                {
                    "exact_snippets": "histologically documented",
                    "criterion": "documentation method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "histologically documented"
                        }
                    ]
                },
                {
                    "exact_snippets": "Stage IV NSCLC",
                    "criterion": "cancer stage and type",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "Stage IV"
                        },
                        {
                            "requirement_type": "type",
                            "expected_value": "NSCLC"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Eligible patients will be required to have positive PD-L1 expression ≥1% by IHC using Dako 22C3 assay.",
            "criterions": [
                {
                    "exact_snippets": "positive PD-L1 expression ≥1% by IHC using Dako 22C3 assay",
                    "criterion": "PD-L1 expression",
                    "requirements": [
                        {
                            "requirement_type": "expression level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients will require a baseline Guardant360 CDx test prior to enrollment",
            "criterions": [
                {
                    "exact_snippets": "baseline Guardant360 CDx test",
                    "criterion": "Guardant360 CDx test",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Patients willing to undergo serial ctDNA testing as required by protocol",
            "criterions": [
                {
                    "exact_snippets": "Patients willing to undergo serial ctDNA testing",
                    "criterion": "willingness to undergo serial ctDNA testing",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Patients will be over the age of 18",
            "criterions": [
                {
                    "exact_snippets": "Patients will be over the age of 18",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": {
                                "operator": ">",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Life expectancy ≥12 weeks",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy ≥12 weeks",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Measurable (RECIST 1.1) indicator lesion not previously irradiated, with measurable disease determined per the treating investigator.",
            "criterions": [
                {
                    "exact_snippets": "Measurable (RECIST 1.1) indicator lesion",
                    "criterion": "indicator lesion",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": "RECIST 1.1"
                        }
                    ]
                },
                {
                    "exact_snippets": "indicator lesion not previously irradiated",
                    "criterion": "indicator lesion",
                    "requirements": [
                        {
                            "requirement_type": "previous irradiation",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "measurable disease determined per the treating investigator",
                    "criterion": "disease",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": "determined per the treating investigator"
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Prior palliative radiotherapy to non-CNS lesions must have been completed at least 2 weeks prior to randomization",
            "criterions": [
                {
                    "exact_snippets": "Prior palliative radiotherapy to non-CNS lesions",
                    "criterion": "palliative radiotherapy to non-CNS lesions",
                    "requirements": [
                        {
                            "requirement_type": "completion time",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. ECOG Performance Score ≤2",
            "criterions": [
                {
                    "exact_snippets": "ECOG Performance Score ≤2",
                    "criterion": "ECOG Performance Score",
                    "requirements": [
                        {
                            "requirement_type": "score",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Adequate organ function",
            "criterions": [
                {
                    "exact_snippets": "Adequate organ function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Hemoglobin > 9 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin > 9 g/dL",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 9,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Platelets > 100,000mm3 or 100 x 109/L",
            "criterions": [
                {
                    "exact_snippets": "Platelets > 100,000mm3 or 100 x 109/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">",
                                        "value": 100000,
                                        "unit": "mm3"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">",
                                        "value": 100,
                                        "unit": "x 10^9/L"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. AST, ALT < 2.5 x ULN with no liver metastases or < 5x ULN with the presence of liver metastases",
            "criterions": [
                {
                    "exact_snippets": "AST, ALT < 2.5 x ULN with no liver metastases",
                    "criterion": "AST, ALT levels",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": "<",
                                "value": 2.5,
                                "unit": "x ULN"
                            }
                        },
                        {
                            "requirement_type": "liver metastases",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "AST, ALT ... < 5x ULN with the presence of liver metastases",
                    "criterion": "AST, ALT levels",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": "<",
                                "value": 5,
                                "unit": "x ULN"
                            }
                        },
                        {
                            "requirement_type": "liver metastases",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Absolute neutrophil count (ANC) > 1500 cells/mm3",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count (ANC) > 1500 cells/mm3",
                    "criterion": "absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 1500,
                                "unit": "cells/mm3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance ≥ 60ml/min calculated by Cockcroft and Gault's equation",
            "criterions": [
                {
                    "exact_snippets": "Creatinine ≤ 1.5 x ULN",
                    "criterion": "creatinine level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "calculated creatinine clearance ≥ 60ml/min calculated by Cockcroft and Gault's equation",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "clearance",
                            "expected_value": {
                                "operator": ">=",
                                "value": 60,
                                "unit": "ml/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Willing to use highly effective contraceptive measures if child-bearing potential or if the patient's sexual partner is a woman of childbearing potential: a. Female subjects should be using a highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to starting of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: i. Post-menopausal is defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments ii. Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the the post-menopausal range for the institution iii. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not a tubal ligation b. Male subjects should be willing to use barrier contraception",
            "criterions": [
                {
                    "exact_snippets": "Willing to use highly effective contraceptive measures if child-bearing potential",
                    "criterion": "use of contraceptive measures",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Female subjects should be using a highly effective contraceptive measures",
                    "criterion": "use of contraceptive measures",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must have a negative pregnancy test",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "not be breast-feeding prior to starting of dosing",
                    "criterion": "breast-feeding",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "evidence of non-child-bearing potential",
                    "criterion": "child-bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Post-menopausal is defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments",
                    "criterion": "post-menopausal status",
                    "requirements": [
                        {
                            "requirement_type": "age",
                            "expected_value": {
                                "operator": ">",
                                "value": 50,
                                "unit": "years"
                            }
                        },
                        {
                            "requirement_type": "amenorrheic duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the the post-menopausal range",
                    "criterion": "post-menopausal status",
                    "requirements": [
                        {
                            "requirement_type": "age",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "years"
                            }
                        },
                        {
                            "requirement_type": "amenorrheic duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "months"
                            }
                        },
                        {
                            "requirement_type": "LH and FSH levels",
                            "expected_value": "post-menopausal range"
                        }
                    ]
                },
                {
                    "exact_snippets": "Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy",
                    "criterion": "surgical sterilization",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Male subjects should be willing to use barrier contraception",
                    "criterion": "use of barrier contraception",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "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. Patients under the age of 18",
            "criterions": [
                {
                    "exact_snippets": "Patients under the age of 18",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Inability to provide informed consent by either the patient or the authorized representative",
            "criterions": [
                {
                    "exact_snippets": "Inability to provide informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients with known EGFR, ALK, ROS1, MET, and RET oncogenic driver alterations that have approved first-line targeted therapies are excluded from the study (All patients must have a tissue or blood-based testing to identify these driver alterations)",
            "criterions": [
                {
                    "exact_snippets": "known EGFR, ALK, ROS1, MET, and RET oncogenic driver alterations",
                    "criterion": "EGFR, ALK, ROS1, MET, and RET oncogenic driver alterations",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "tissue or blood-based testing to identify these driver alterations",
                    "criterion": "tissue or blood-based testing",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Patients with no detectable ctDNA or ctDNA VAF ≤ 0.3% on Guardant360 CDx at baseline",
            "criterions": [
                {
                    "exact_snippets": "no detectable ctDNA",
                    "criterion": "ctDNA",
                    "requirements": [
                        {
                            "requirement_type": "detectability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "ctDNA VAF ≤ 0.3%",
                    "criterion": "ctDNA VAF",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 0.3,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Subjects with untreated CNS metastases are excluded.",
            "criterions": [
                {
                    "exact_snippets": "untreated CNS metastases",
                    "criterion": "CNS metastases",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "untreated"
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to randomization. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization.",
            "criterions": [
                {
                    "exact_snippets": "CNS metastases are adequately treated",
                    "criterion": "CNS metastases",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "adequately treated"
                        }
                    ]
                },
                {
                    "exact_snippets": "neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to randomization",
                    "criterion": "neurological status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "returned to baseline"
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "off corticosteroids",
                    "criterion": "corticosteroid use",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "off"
                        }
                    ]
                },
                {
                    "exact_snippets": "on a stable or decreasing dose of 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization",
                    "criterion": "corticosteroid use",
                    "requirements": [
                        {
                            "requirement_type": "dose stability",
                            "expected_value": "stable or decreasing"
                        },
                        {
                            "requirement_type": "dose",
                            "expected_value": {
                                "operator": "=",
                                "value": 10,
                                "unit": "mg"
                            }
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Subjects with carcinomatous meningitis",
            "criterions": [
                {
                    "exact_snippets": "Subjects with carcinomatous meningitis",
                    "criterion": "carcinomatous meningitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before randomization",
            "criterions": [
                {
                    "exact_snippets": "recovered from the effects of major surgery",
                    "criterion": "recovery from major surgery",
                    "requirements": [
                        {
                            "requirement_type": "time since recovery",
                            "expected_value": {
                                "operator": ">=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "recovered from the effects of ... significant traumatic injury",
                    "criterion": "recovery from significant traumatic injury",
                    "requirements": [
                        {
                            "requirement_type": "time since recovery",
                            "expected_value": {
                                "operator": ">=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Subjects with previous malignancies (except non-melanoma skin cancers, and in situ cancers such as the following: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to randomization and no additional therapy is required or anticipated to be needed during the study period.",
            "criterions": [
                {
                    "exact_snippets": "Subjects with previous malignancies",
                    "criterion": "previous malignancies",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "except non-melanoma skin cancers",
                    "criterion": "non-melanoma skin cancers",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "in situ cancers such as the following: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast",
                    "criterion": "in situ cancers",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "complete remission was achieved at least 2 years prior to randomization",
                    "criterion": "complete remission",
                    "requirements": [
                        {
                            "requirement_type": "time since remission",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "no additional therapy is required or anticipated to be needed during the study period",
                    "criterion": "additional therapy",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Other active malignancy requiring concurrent intervention.",
            "criterions": [
                {
                    "exact_snippets": "Other active malignancy requiring concurrent intervention.",
                    "criterion": "active malignancy",
                    "requirements": [
                        {
                            "requirement_type": "intervention",
                            "expected_value": "concurrent"
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Subjects with an active, known, or suspected autoimmune disease. Subjects with type I diabetes mellitus, and hypothyroidism only require hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.",
            "criterions": [
                {
                    "exact_snippets": "active, known, or suspected autoimmune disease",
                    "criterion": "autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "active",
                                "known",
                                "suspected"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "type I diabetes mellitus",
                    "criterion": "type I diabetes mellitus",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hypothyroidism only require hormone replacement",
                    "criterion": "hypothyroidism",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "hormone replacement"
                        }
                    ]
                },
                {
                    "exact_snippets": "skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment",
                    "criterion": "skin disorders",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "not requiring systemic treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "conditions not expected to recur in the absence of an external trigger",
                    "criterion": "conditions not expected to recur",
                    "requirements": [
                        {
                            "requirement_type": "trigger",
                            "expected_value": "absence of an external trigger"
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroids > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.",
            "criterions": [
                {
                    "exact_snippets": "condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization",
                    "criterion": "systemic treatment with corticosteroids or immunosuppressive medications",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Inhaled or topical steroids, and adrenal replacement steroids > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease",
                    "criterion": "active autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.",
            "criterions": [
                {
                    "exact_snippets": "interstitial lung disease that is symptomatic",
                    "criterion": "interstitial lung disease",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "interstitial lung disease ... may interfere with the detection or management of suspected drug-related pulmonary toxicity",
                    "criterion": "interstitial lung disease",
                    "requirements": [
                        {
                            "requirement_type": "interference with detection or management of drug-related pulmonary toxicity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Significant uncontrolled cardiovascular disease, including but not limited to, any of the following:",
            "criterions": [
                {
                    "exact_snippets": "Significant uncontrolled cardiovascular disease",
                    "criterion": "cardiovascular disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Uncontrolled hypertension, which is defined as systolic blood pressure > 160 mm Hg or diastolic blood pressure > 100 mm Hg despite optimal medical management.",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled hypertension, which is defined as systolic blood pressure > 160 mm Hg",
                    "criterion": "systolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 160,
                                "unit": "mm Hg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled hypertension, which is defined as ... diastolic blood pressure > 100 mm Hg",
                    "criterion": "diastolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 100,
                                "unit": "mm Hg"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Active coronary artery disease, including unstable all newly diagnosed angina within 3 months of study enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Active coronary artery disease",
                    "criterion": "coronary artery disease",
                    "requirements": [
                        {
                            "requirement_type": "activity status",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable all newly diagnosed angina within 3 months of study enrollment",
                    "criterion": "angina",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": "unstable"
                        },
                        {
                            "requirement_type": "diagnosis timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Myocardial infarction in the past 6 months.",
            "criterions": [
                {
                    "exact_snippets": "Myocardial infarction in the past 6 months",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. History of congenital long QT syndrome.",
            "criterions": [
                {
                    "exact_snippets": "History of congenital long QT syndrome",
                    "criterion": "congenital long QT syndrome",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. History of clinically significant arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or torsade de pointes.",
            "criterions": [
                {
                    "exact_snippets": "History of clinically significant arrhythmias",
                    "criterion": "clinically significant arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ventricular tachycardia",
                    "criterion": "ventricular tachycardia",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ventricular fibrillation",
                    "criterion": "ventricular fibrillation",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "torsade de pointes",
                    "criterion": "torsade de pointes",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Uncontrolled heart failure, defined as class III of 4 by the New York Heart Association functional classification.",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled heart failure",
                    "criterion": "heart failure",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "class III of 4 by the New York Heart Association functional classification",
                    "criterion": "New York Heart Association functional classification",
                    "requirements": [
                        {
                            "requirement_type": "class",
                            "expected_value": "III of 4"
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. History of a current diagnosis of myocarditis.",
            "criterions": [
                {
                    "exact_snippets": "History of a current diagnosis of myocarditis",
                    "criterion": "myocarditis",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. the Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.",
            "criterions": [
                {
                    "exact_snippets": "Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.",
                    "criterion": "medical condition",
                    "requirements": [
                        {
                            "requirement_type": "risk",
                            "expected_value": "increase"
                        },
                        {
                            "requirement_type": "interference",
                            "expected_value": "interpretation of safety results"
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection",
            "criterions": [
                {
                    "exact_snippets": "positive test for hepatitis B virus",
                    "criterion": "hepatitis B virus",
                    "requirements": [
                        {
                            "requirement_type": "test result",
                            "expected_value": "positive"
                        },
                        {
                            "requirement_type": "infection status",
                            "expected_value": [
                                "acute",
                                "chronic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "positive test for ... hepatitis C virus",
                    "criterion": "hepatitis C virus",
                    "requirements": [
                        {
                            "requirement_type": "test result",
                            "expected_value": "positive"
                        },
                        {
                            "requirement_type": "infection status",
                            "expected_value": [
                                "acute",
                                "chronic"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Subjects with Grade 2 peripheral neuropathy",
            "criterions": [
                {
                    "exact_snippets": "Grade 2 peripheral neuropathy",
                    "criterion": "peripheral neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "Grade 2"
                        }
                    ]
                }
            ]
        },
        {
            "line": "18. Life expectancy <12 weeks",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy <12 weeks",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": {
                                "operator": "<",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "14. Total bilirubin < 1.5 x ULN if no liver metastases or < 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin < 1.5 x ULN if no liver metastases",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Total bilirubin < 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia)",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Total bilirubin < 3 x ULN ... liver metastases",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}