{
    "info": {
        "nct_id": "NCT04304248",
        "official_title": "A Phase II Study of Neoadjuvant Toripalimab Plus Platinum-based Doublet for Potentially Resectable Stage III Non-small Cell Lung Cancer",
        "inclusion_criteria": "1. Previously untreated patients with histologically- or cytologically- documented NSCLC who present stage IIIA disease (according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology) and also, potentially resectable locally advanced NSCLC patients' stage IIIB with T3N2 disease according to 8th edition can be included.\n\n   PET/CT including IV contrast (CT of diagnostic quality) will be performed at baseline (28 days +10 before randomization);\n2. Tumor should be EGFR wild-type or EML4-ALK negative;\n3. Tumor should be considered resectable before study entry by a multidisciplinary team;\n4. ECOG (Performance status) 0-1;\n5. Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to randomization.\n\n   i. Neutrophils ≥ 1500×109/L ii. Platelets ≥ 100 x×109/L iii. Hemoglobin > 9.0 g/dL iv. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min v. AST/ALT ≤ 3 x ULN vi. Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) vii. The patients need to have a forced expiratory volume (FEV1) ≥ 1.2 liters or >40% predicted value viii. INR/APTT within normal limits;\n6. All patients are notified of the investigational nature of this study and signed a written informed consent in accordance with institutional and national guidelines, including the Declaration of Helsinki prior to any trial-related intervention;\n7. Patients aged > 18 years;\n8. Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine pregnancy test within 7 days before randomization.\n\n   All sexually active men and women of childbearing potential must use an effective contraceptive method (two barrier methods or a barrier method plus a hormonal method) during the study treatment and for a period of at least 12 months following the last administration of trial drugs;\n9. Patient capable of proper therapeutic compliance and accessible for correct follow-up;\n10. Measurable or evaluable disease (according to RECIST 1.1 criteria).\nHealthy volunteers allowed\nMust have minimum age of 18 Years\nMust have maximum age of 80 Years",
        "exclusion_criteria": "1. All patients carrying activating mutations in the TK domain of EGFR or any variety of alterations in the ALK gene.\n2. Patients with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement or unexpected conditions of recurrence in the absence of an external trigger are allowed to be included.\n3. Patients 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 steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.\n4. Patients with a history of interstitial lung disease cannot be included if they have symptomatic ILD (Grade 3-4) and/or poor lung function. In case of doubt please contact trial team.\n5. Patients with other active malignancy requiring concurrent intervention and/or concurrent treatment with other investigational drugs or anti-cancer therapy\n6. Patients with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period.\n7. Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or understand the patient information\n8. Patients who have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways\n9. Patients with positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection\n10. Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)\n11. Patients with history of allergy to study drug components excipients\n12. Women who are pregnant or in the period of breastfeeding\n13. Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Previously untreated patients with histologically- or cytologically- documented NSCLC who present stage IIIA disease (according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology) and also, potentially resectable locally advanced NSCLC patients' stage IIIB with T3N2 disease according to 8th edition can be included.",
            "criterions": [
                {
                    "exact_snippets": "Previously untreated patients",
                    "criterion": "treatment history",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "untreated"
                        }
                    ]
                },
                {
                    "exact_snippets": "histologically- or cytologically- documented NSCLC",
                    "criterion": "NSCLC documentation",
                    "requirements": [
                        {
                            "requirement_type": "documentation method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "stage IIIA disease (according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology)",
                    "criterion": "NSCLC stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "IIIA"
                        }
                    ]
                },
                {
                    "exact_snippets": "potentially resectable locally advanced NSCLC patients' stage IIIB with T3N2 disease according to 8th edition",
                    "criterion": "NSCLC stage and resectability",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "IIIB"
                        },
                        {
                            "requirement_type": "resectability",
                            "expected_value": "potentially resectable"
                        },
                        {
                            "requirement_type": "disease classification",
                            "expected_value": "T3N2"
                        }
                    ]
                }
            ]
        },
        {
            "line": "PET/CT including IV contrast (CT of diagnostic quality) will be performed at baseline (28 days +10 before randomization);",
            "criterions": [
                {
                    "exact_snippets": "PET/CT including IV contrast (CT of diagnostic quality)",
                    "criterion": "PET/CT scan",
                    "requirements": [
                        {
                            "requirement_type": "contrast",
                            "expected_value": "IV"
                        },
                        {
                            "requirement_type": "quality",
                            "expected_value": "diagnostic"
                        }
                    ]
                },
                {
                    "exact_snippets": "will be performed at baseline (28 days +10 before randomization)",
                    "criterion": "timing of PET/CT scan",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "baseline (28 days +10 before randomization)"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Tumor should be EGFR wild-type or EML4-ALK negative;",
            "criterions": [
                {
                    "exact_snippets": "Tumor should be EGFR wild-type",
                    "criterion": "EGFR status",
                    "requirements": [
                        {
                            "requirement_type": "mutation",
                            "expected_value": "wild-type"
                        }
                    ]
                },
                {
                    "exact_snippets": "Tumor should be ... EML4-ALK negative",
                    "criterion": "EML4-ALK status",
                    "requirements": [
                        {
                            "requirement_type": "mutation",
                            "expected_value": "negative"
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Tumor should be considered resectable before study entry by a multidisciplinary team;",
            "criterions": [
                {
                    "exact_snippets": "Tumor should be considered resectable",
                    "criterion": "tumor resectability",
                    "requirements": [
                        {
                            "requirement_type": "consideration",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "before study entry",
                    "criterion": "timing of tumor resectability consideration",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "before study entry"
                        }
                    ]
                },
                {
                    "exact_snippets": "by a multidisciplinary team",
                    "criterion": "evaluation team for tumor resectability",
                    "requirements": [
                        {
                            "requirement_type": "team composition",
                            "expected_value": "multidisciplinary"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. ECOG (Performance status) 0-1;",
            "criterions": [
                {
                    "exact_snippets": "ECOG (Performance status) 0-1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to randomization.",
            "criterions": [
                {
                    "exact_snippets": "Screening laboratory values must meet the following criteria",
                    "criterion": "screening laboratory values",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": "must meet the following criteria"
                        }
                    ]
                },
                {
                    "exact_snippets": "obtained within 14 days prior to randomization",
                    "criterion": "screening laboratory values",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "i. Neutrophils ≥ 1500×109/L ii. Platelets ≥ 100 x×109/L iii. Hemoglobin > 9.0 g/dL iv. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min v. AST/ALT ≤ 3 x ULN vi. Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) vii. The patients need to have a forced expiratory volume (FEV1) ≥ 1.2 liters or >40% predicted value viii. INR/APTT within normal limits;",
            "criterions": [
                {
                    "exact_snippets": "Neutrophils ≥ 1500×109/L",
                    "criterion": "neutrophils",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1500,
                                "unit": "×109/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Platelets ≥ 100 x×109/L",
                    "criterion": "platelets",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "x×109/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Hemoglobin > 9.0 g/dL",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 9.0,
                                "unit": "g/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Serum creatinine ≤ 1.5 x ULN",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinine clearance (CrCl) ≥ 40 mL/min",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 40,
                                "unit": "mL/min"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "AST/ALT ≤ 3 x ULN",
                    "criterion": "AST/ALT",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Total Bilirubin ≤ 1.5 x ULN",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL",
                    "criterion": "total bilirubin in subjects with Gilbert Syndrome",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 3.0,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "forced expiratory volume (FEV1) ≥ 1.2 liters",
                    "criterion": "forced expiratory volume (FEV1)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.2,
                                "unit": "liters"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "forced expiratory volume (FEV1) ... >40% predicted value",
                    "criterion": "forced expiratory volume (FEV1)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 40,
                                "unit": "% predicted value"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "INR/APTT within normal limits",
                    "criterion": "INR/APTT",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "within normal limits"
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. All patients are notified of the investigational nature of this study and signed a written informed consent in accordance with institutional and national guidelines, including the Declaration of Helsinki prior to any trial-related intervention;",
            "criterions": [
                {
                    "exact_snippets": "notified of the investigational nature of this study",
                    "criterion": "notification of investigational nature",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "signed a written informed consent",
                    "criterion": "written informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "in accordance with institutional and national guidelines, including the Declaration of Helsinki",
                    "criterion": "compliance with guidelines",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Patients aged > 18 years;",
            "criterions": [
                {
                    "exact_snippets": "Patients aged > 18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine pregnancy test within 7 days before randomization.",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "women who had their last menstrual period in the last 2 years",
                    "criterion": "last menstrual period",
                    "requirements": [
                        {
                            "requirement_type": "time since last period",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "must have a negative serum or urine pregnancy test",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "within 7 days before randomization",
                    "criterion": "timing of pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 7,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "All sexually active men and women of childbearing potential must use an effective contraceptive method (two barrier methods or a barrier method plus a hormonal method) during the study treatment and for a period of at least 12 months following the last administration of trial drugs;",
            "criterions": [
                {
                    "exact_snippets": "sexually active men and women of childbearing potential",
                    "criterion": "sexually active status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "use an effective contraceptive method",
                    "criterion": "contraceptive method usage",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "two barrier methods or a barrier method plus a hormonal method",
                    "criterion": "contraceptive method type",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "two barrier methods",
                                "a barrier method plus a hormonal method"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "during the study treatment and for a period of at least 12 months following the last administration of trial drugs",
                    "criterion": "contraceptive method duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "during the study treatment and for a period of at least 12 months following the last administration of trial drugs"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Patient capable of proper therapeutic compliance and accessible for correct follow-up;",
            "criterions": [
                {
                    "exact_snippets": "Patient capable of proper therapeutic compliance",
                    "criterion": "therapeutic compliance",
                    "requirements": [
                        {
                            "requirement_type": "capability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "accessible for correct follow-up",
                    "criterion": "follow-up accessibility",
                    "requirements": [
                        {
                            "requirement_type": "accessibility",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Measurable or evaluable disease (according to RECIST 1.1 criteria).",
            "criterions": [
                {
                    "exact_snippets": "Measurable or evaluable disease (according to RECIST 1.1 criteria)",
                    "criterion": "disease",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": [
                                "measurable",
                                "evaluable"
                            ]
                        },
                        {
                            "requirement_type": "criteria",
                            "expected_value": "RECIST 1.1"
                        }
                    ]
                }
            ]
        },
        {
            "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"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 80 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 80 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 80,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. All patients carrying activating mutations in the TK domain of EGFR or any variety of alterations in the ALK gene.",
            "criterions": [
                {
                    "exact_snippets": "activating mutations in the TK domain of EGFR",
                    "criterion": "EGFR TK domain mutations",
                    "requirements": [
                        {
                            "requirement_type": "mutation type",
                            "expected_value": "activating"
                        }
                    ]
                },
                {
                    "exact_snippets": "alterations in the ALK gene",
                    "criterion": "ALK gene alterations",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Patients with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement or unexpected conditions of recurrence in the absence of an external trigger are allowed to be included.",
            "criterions": [
                {
                    "exact_snippets": "active, known or suspected autoimmune disease",
                    "criterion": "autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "active",
                                "known",
                                "suspected"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "vitiligo",
                    "criterion": "vitiligo",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "type I diabetes mellitus",
                    "criterion": "type I diabetes mellitus",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement",
                    "criterion": "residual hypothyroidism due to autoimmune thyroiditis",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "hormone replacement"
                        }
                    ]
                },
                {
                    "exact_snippets": "unexpected conditions of recurrence in the absence of an external trigger",
                    "criterion": "unexpected conditions of recurrence",
                    "requirements": [
                        {
                            "requirement_type": "trigger",
                            "expected_value": "absence of an external trigger"
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients 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 steroid doses > 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": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Inhaled or topical steroids, and adrenal replacement steroid doses > 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": "4. Patients with a history of interstitial lung disease cannot be included if they have symptomatic ILD (Grade 3-4) and/or poor lung function. In case of doubt please contact trial team.",
            "criterions": [
                {
                    "exact_snippets": "history of interstitial lung disease",
                    "criterion": "history of interstitial lung disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "symptomatic ILD (Grade 3-4)",
                    "criterion": "symptomatic ILD",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "poor lung function",
                    "criterion": "lung function",
                    "requirements": [
                        {
                            "requirement_type": "quality",
                            "expected_value": "poor"
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Patients with other active malignancy requiring concurrent intervention and/or concurrent treatment with other investigational drugs or anti-cancer therapy",
            "criterions": [
                {
                    "exact_snippets": "Patients with other active malignancy requiring concurrent intervention",
                    "criterion": "other active malignancy",
                    "requirements": [
                        {
                            "requirement_type": "intervention requirement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "concurrent treatment with other investigational drugs",
                    "criterion": "treatment with other investigational drugs",
                    "requirements": [
                        {
                            "requirement_type": "concurrent treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "concurrent treatment with ... anti-cancer therapy",
                    "criterion": "treatment with anti-cancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "concurrent treatment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Patients with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period.",
            "criterions": [
                {
                    "exact_snippets": "Patients 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: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast",
                    "criterion": "in situ cancers",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "types",
                            "expected_value": [
                                "bladder",
                                "gastric",
                                "colon",
                                "endometrial",
                                "cervical/dysplasia",
                                "melanoma",
                                "breast"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "complete remission was achieved at least 2 years prior to study entry",
                    "criterion": "complete remission",
                    "requirements": [
                        {
                            "requirement_type": "time since remission",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "no additional therapy is required during the study period",
                    "criterion": "additional therapy",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or understand the patient information",
            "criterions": [
                {
                    "exact_snippets": "Any medical, mental or psychological condition",
                    "criterion": "medical, mental or psychological condition",
                    "requirements": [
                        {
                            "requirement_type": "impact on study completion or understanding",
                            "expected_value": "would not permit the patient to complete the study or understand the patient information"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Patients with positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection",
            "criterions": [
                {
                    "exact_snippets": "positive test for hepatitis B virus surface antigen (HBV sAg)",
                    "criterion": "hepatitis B virus surface antigen (HBV sAg)",
                    "requirements": [
                        {
                            "requirement_type": "test result",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "positive test for ... hepatitis C virus ribonucleic acid (HCV antibody)",
                    "criterion": "hepatitis C virus ribonucleic acid (HCV antibody)",
                    "requirements": [
                        {
                            "requirement_type": "test result",
                            "expected_value": "positive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)",
            "criterions": [
                {
                    "exact_snippets": "known history of testing positive for human immunodeficiency virus (HIV)",
                    "criterion": "HIV status",
                    "requirements": [
                        {
                            "requirement_type": "history of positive test",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "known acquired immunodeficiency syndrome (AIDS)",
                    "criterion": "AIDS status",
                    "requirements": [
                        {
                            "requirement_type": "known status",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Patients with history of allergy to study drug components excipients",
            "criterions": [
                {
                    "exact_snippets": "history of allergy to study drug components excipients",
                    "criterion": "allergy to study drug components",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Women who are pregnant or in the period of breastfeeding",
            "criterions": [
                {
                    "exact_snippets": "Women who are pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "in the period of breastfeeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study",
            "criterions": [
                {
                    "exact_snippets": "Sexually active men and women",
                    "criterion": "sexual activity",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "men and women of childbearing potential",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "of childbearing potential"
                        }
                    ]
                },
                {
                    "exact_snippets": "not willing to use an effective contraceptive method during the study",
                    "criterion": "contraceptive use",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [
        {
            "line": "8. Patients who have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways",
            "criterions": [
                {
                    "exact_snippets": "prior treatment with an anti-PD-1",
                    "criterion": "prior treatment with anti-PD-1 antibody",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "prior treatment with an anti-PD-L1",
                    "criterion": "prior treatment with anti-PD-L1 antibody",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "prior treatment with an anti-PD-L2",
                    "criterion": "prior treatment with anti-PD-L2 antibody",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "prior treatment with an anti-CTLA-4 antibody",
                    "criterion": "prior treatment with anti-CTLA-4 antibody",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "prior treatment with ... any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways",
                    "criterion": "prior treatment with antibody or drug targeting T-cell costimulation or immune checkpoint pathways",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}