{
    "info": {
        "nct_id": "NCT03193931",
        "official_title": "A Randomized Phase II Study Comparing Pembrolizumab With Methotrexate in Elderly, Frail or Cisplatin-ineligible Patients With Head and Neck Cancers",
        "inclusion_criteria": "1. Cooperation and willingness to complete all aspects of the study\n2. Signed written informed consent must be given prior to study inclusion\n3. Histological or cytological confirmed recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) not amenable to local therapies\n4. Progressive disease at study entry\n5. At least 1 measurable lesion according to RECIST 1.1\n6. No previous systemic treatment for metastatic disease\n7. Not eligible for cisplatin-based chemotherapy, defined as:\n\n   * ECOG 2 [Eastern Cooperative Oncology Group] and/or\n   * Calculated CrCl [Creatinine Clearance] <60 mL/min (measured by MDRD)\n8. Age ≥ 18 years\n9. ECOG performance status 0 - 2\n10. Brain metastases require completion of local therapy with discontinuation of steroids prior to start of treatment\n11. If of childbearing potential, willingness to use highly effective contraceptive method for the duration of the study and 120 days after last dose, such as combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), vasectomized partner, bilateral tubal occlusion, sexual abstinence. If an oral contraception is used, a barrier method of contraception (e.g. male condom, female condom, cervical cap, diaphragm, contraceptive sponge) has to be applied additionally.\n12. Adequate bone marrow function, liver and renal function:\n\n    1. Absolute neutrophil count ≥ 1.5 x 109/L\n    2. Thrombocytes ≥ 100 x 109/L\n    3. Hemoglobin ≥ 9 g/dL\n    4. INR [international normalized ratio] ≤ 1.5 and PPT [partial prothrombin time] ≤ 1.5 x lower limit during the last 7 days before therapy\n    5. Bilirubin < 1.5 x lower limit and\n    6. AST (GOT) [aspartate aminotransferase] and ALT (GPT) [alanine transaminase] < 3 x lower limit (5 x lower limit in case of liver metastases)\n13. Tumor block or 20 slides must be available at study inclusion for central pathology testing\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Live expectancy less than 3 months\n2. Nasopharynx carcinoma\n3. Anticancer treatment during the last 30 days prior to start of treatment, including systemic therapy, radiotherapy or major surgery\n4. Participation in a clinical trial within the last 30 days prior to study treatment\n5. History of allogeneic tissue/solid organ transplant\n6. History of pneumonitis that has required oral or i.v. steroids\n7. Evidence of interstitial lung disease\n8. Minor surgery ≤ 24 hours prior first dose of study treatment\n9. Symptomatic acute cardiovascular or cerebrovascular disease\n10. Known active HBV [hepatitis B virus], HCV [hepatitis C virus] or HIV infection\n11. Has any other active infection requiring systemic therapy.\n12. Patients with active tuberculosis\n13. Prior therapy with an anti-Programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-Programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor (TNFR) family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)\n14. A diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.\n15. Patient has had a prior monoclonal antibody, which does significantly interfere with the immune system or which does have a systemic therapeutic effect on the tumor within 4 weeks prior to randomization.\n16. Patient has not recovered (i.e., ≤ Grade 1 or at baseline) from any toxicity due to agents administered more than 4 weeks earlier. [Subjects with ≤ Grade 2 neuropathy or alopecia are an exception to this criterion and may qualify for the study.]\n17. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.\n18. Has received a live vaccine within 30 days prior to the first dose of trial treatment.\n19. Has known hypersensitivity to methotrexate or pembrolizumab or any constituent of the products..\n20. Other active malignancy requiring treatment\n21. Lactating or pregnant women, women of child-bearing potential who do not agree to the usage of highly effective contraception methods (allowed methods of contraception, meaning methods with a rate of failure of less than 1% per year are combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), vasectomized partner, bilateral tubal occlusion, sexual abstinence. If an oral contraception is used, a barrier method of contraception (e.g. male condom, female condom, cervical cap, diaphragm, contraceptive sponge) has to be applied additionally). Women of childbearing potential must have a negative pregnancy test (serum β-hCG) at Screening.\n22. Any psychiatric illness that would affect the patient's ability to understand the demands of the clinical trial\n23. Patient has already been recruited in this trial (does not include screening failures)\n24. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.\n25. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "identified_line": {
                "line": "1. Cooperation and willingness to complete all aspects of the study",
                "criterions": [
                    {
                        "exact_snippets": "Cooperation and willingness to complete all aspects of the study",
                        "criterion": "cooperation and willingness",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "Cooperation and willingness to complete all aspects of the study",
                        "criterion": "cooperation and willingness",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "2. Signed written informed consent must be given prior to study inclusion",
                "criterions": [
                    {
                        "exact_snippets": "Signed written informed consent must be given",
                        "criterion": "informed consent",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "Signed written informed consent must be given",
                        "criterion": "informed consent",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "7. Not eligible for cisplatin-based chemotherapy, defined as:",
                "criterions": [
                    {
                        "exact_snippets": "Not eligible for cisplatin-based chemotherapy",
                        "criterion": "cisplatin-based chemotherapy eligibility",
                        "requirement": {
                            "requirement_type": "eligibility",
                            "expected_value": false
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "Not eligible for cisplatin-based chemotherapy",
                        "criterion": "cisplatin-based chemotherapy eligibility",
                        "requirement": {
                            "requirement_type": "eligibility",
                            "expected_value": false
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "* ECOG 2 [Eastern Cooperative Oncology Group] and/or",
                "criterions": [
                    {
                        "exact_snippets": "ECOG 2 [Eastern Cooperative Oncology Group]",
                        "criterion": "ECOG performance status",
                        "requirement": {
                            "requirement_type": "value",
                            "expected_value": "2"
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "or_criteria": [
                            {
                                "exact_snippets": "ECOG 2 [Eastern Cooperative Oncology Group]",
                                "criterion": "ECOG performance status",
                                "requirement": {
                                    "requirement_type": "value",
                                    "expected_value": "2"
                                }
                            }
                        ]
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "* Calculated CrCl [Creatinine Clearance] <60 mL/min (measured by MDRD)",
                "criterions": [
                    {
                        "exact_snippets": "Calculated CrCl [Creatinine Clearance] <60 mL/min",
                        "criterion": "Creatinine Clearance",
                        "requirement": {
                            "requirement_type": "measurement",
                            "expected_value": {
                                "operator": "<",
                                "value": 60,
                                "unit": "mL/min"
                            }
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "Calculated CrCl [Creatinine Clearance] <60 mL/min",
                        "criterion": "Creatinine Clearance",
                        "requirement": {
                            "requirement_type": "measurement",
                            "expected_value": {
                                "operator": "<",
                                "value": 60,
                                "unit": "mL/min"
                            }
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "8. Age ≥ 18 years",
                "criterions": [
                    {
                        "exact_snippets": "Age ≥ 18 years",
                        "criterion": "age",
                        "requirement": {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "Age ≥ 18 years",
                        "criterion": "age",
                        "requirement": {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "9. ECOG performance status 0 - 2",
                "criterions": [
                    {
                        "exact_snippets": "ECOG performance status 0 - 2",
                        "criterion": "ECOG performance status",
                        "requirement": {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "ECOG performance status 0 - 2",
                        "criterion": "ECOG performance status",
                        "requirement": {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "10. Brain metastases require completion of local therapy with discontinuation of steroids prior to start of treatment",
                "criterions": [
                    {
                        "exact_snippets": "Brain metastases require completion of local therapy",
                        "criterion": "brain metastases",
                        "requirement": {
                            "requirement_type": "local therapy completion",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "discontinuation of steroids prior to start of treatment",
                        "criterion": "steroid use",
                        "requirement": {
                            "requirement_type": "discontinuation",
                            "expected_value": true
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "Brain metastases require completion of local therapy",
                        "criterion": "brain metastases",
                        "requirement": {
                            "requirement_type": "local therapy completion",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "discontinuation of steroids prior to start of treatment",
                        "criterion": "steroid use",
                        "requirement": {
                            "requirement_type": "discontinuation",
                            "expected_value": true
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "11. If of childbearing potential, willingness to use highly effective contraceptive method for the duration of the study and 120 days after last dose, such as combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), vasectomized partner, bilateral tubal occlusion, sexual abstinence. If an oral contraception is used, a barrier method of contraception (e.g. male condom, female condom, cervical cap, diaphragm, contraceptive sponge) has to be applied additionally.",
                "criterions": [
                    {
                        "exact_snippets": "If of childbearing potential",
                        "criterion": "childbearing potential",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "willingness to use highly effective contraceptive method for the duration of the study and 120 days after last dose",
                        "criterion": "use of highly effective contraceptive method",
                        "requirement": {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "If an oral contraception is used, a barrier method of contraception (e.g. male condom, female condom, cervical cap, diaphragm, contraceptive sponge) has to be applied additionally",
                        "criterion": "use of barrier method of contraception",
                        "requirement": {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    }
                ]
            },
            "logical_structure": {
                "condition": {
                    "exact_snippets": "If of childbearing potential",
                    "criterion": "childbearing potential",
                    "requirement": {
                        "requirement_type": "presence",
                        "expected_value": true
                    }
                },
                "then_criteria": {
                    "and_criteria": [
                        {
                            "exact_snippets": "willingness to use highly effective contraceptive method for the duration of the study and 120 days after last dose",
                            "criterion": "use of highly effective contraceptive method",
                            "requirement": {
                                "requirement_type": "willingness",
                                "expected_value": true
                            }
                        },
                        {
                            "condition": {
                                "exact_snippets": "use of highly effective contraceptive method",
                                "criterion": "use of highly effective contraceptive method",
                                "requirement": {
                                    "requirement_type": "presence",
                                    "expected_value": "oral contraception"
                                }
                            },
                            "then_criteria": {
                                "exact_snippets": "If an oral contraception is used, a barrier method of contraception (e.g. male condom, female condom, cervical cap, diaphragm, contraceptive sponge) has to be applied additionally",
                                "criterion": "use of barrier method of contraception",
                                "requirement": {
                                    "requirement_type": "necessity",
                                    "expected_value": true
                                }
                            },
                            "else_criteria": null
                        }
                    ]
                },
                "else_criteria": null
            }
        },
        {
            "identified_line": {
                "line": "1. Absolute neutrophil count ≥ 1.5 x 109/L",
                "criterions": [
                    {
                        "exact_snippets": "Absolute neutrophil count ≥ 1.5 x 109/L",
                        "criterion": "absolute neutrophil count",
                        "requirement": {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "x 10^9/L"
                            }
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "Absolute neutrophil count ≥ 1.5 x 109/L",
                        "criterion": "absolute neutrophil count",
                        "requirement": {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "x 10^9/L"
                            }
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "2. Thrombocytes ≥ 100 x 109/L",
                "criterions": [
                    {
                        "exact_snippets": "Thrombocytes ≥ 100 x 109/L",
                        "criterion": "thrombocytes",
                        "requirement": {
                            "requirement_type": "count",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "x 10^9/L"
                            }
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "Thrombocytes ≥ 100 x 109/L",
                        "criterion": "thrombocytes",
                        "requirement": {
                            "requirement_type": "count",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "x 10^9/L"
                            }
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "3. Hemoglobin ≥ 9 g/dL",
                "criterions": [
                    {
                        "exact_snippets": "Hemoglobin ≥ 9 g/dL",
                        "criterion": "hemoglobin",
                        "requirement": {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9,
                                "unit": "g/dL"
                            }
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "Hemoglobin ≥ 9 g/dL",
                        "criterion": "hemoglobin",
                        "requirement": {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9,
                                "unit": "g/dL"
                            }
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "4. INR [international normalized ratio] ≤ 1.5 and PPT [partial prothrombin time] ≤ 1.5 x lower limit during the last 7 days before therapy",
                "criterions": [
                    {
                        "exact_snippets": "INR [international normalized ratio] ≤ 1.5",
                        "criterion": "INR",
                        "requirement": {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "N/A"
                            }
                        }
                    },
                    {
                        "exact_snippets": "PPT [partial prothrombin time] ≤ 1.5 x lower limit",
                        "criterion": "PPT",
                        "requirement": {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x lower limit"
                            }
                        }
                    },
                    {
                        "exact_snippets": "during the last 7 days before therapy",
                        "criterion": "time frame",
                        "requirement": {
                            "requirement_type": "time frame",
                            "expected_value": "last 7 days before therapy"
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "and_criteria": [
                            {
                                "exact_snippets": "INR [international normalized ratio] ≤ 1.5",
                                "criterion": "INR",
                                "requirement": {
                                    "requirement_type": "value",
                                    "expected_value": {
                                        "operator": "<=",
                                        "value": 1.5,
                                        "unit": "N/A"
                                    }
                                }
                            },
                            {
                                "exact_snippets": "PPT [partial prothrombin time] ≤ 1.5 x lower limit",
                                "criterion": "PPT",
                                "requirement": {
                                    "requirement_type": "value",
                                    "expected_value": {
                                        "operator": "<=",
                                        "value": 1.5,
                                        "unit": "x lower limit"
                                    }
                                }
                            }
                        ]
                    },
                    {
                        "exact_snippets": "during the last 7 days before therapy",
                        "criterion": "time frame",
                        "requirement": {
                            "requirement_type": "time frame",
                            "expected_value": "last 7 days before therapy"
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "5. Bilirubin < 1.5 x lower limit and",
                "criterions": [
                    {
                        "exact_snippets": "Bilirubin < 1.5 x lower limit",
                        "criterion": "bilirubin level",
                        "requirement": {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "x lower limit"
                            }
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "Bilirubin < 1.5 x lower limit",
                        "criterion": "bilirubin level",
                        "requirement": {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "x lower limit"
                            }
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "6. AST (GOT) [aspartate aminotransferase] and ALT (GPT) [alanine transaminase] < 3 x lower limit (5 x lower limit in case of liver metastases)",
                "criterions": [
                    {
                        "exact_snippets": "AST (GOT) [aspartate aminotransferase] ... < 3 x lower limit (5 x lower limit in case of liver metastases)",
                        "criterion": "AST (GOT) [aspartate aminotransferase]",
                        "requirement": {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 3,
                                        "unit": "x lower limit"
                                    }
                                ]
                            }
                        }
                    },
                    {
                        "exact_snippets": "ALT (GPT) [alanine transaminase] ... < 3 x lower limit (5 x lower limit in case of liver metastases)",
                        "criterion": "ALT (GPT) [alanine transaminase]",
                        "requirement": {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 3,
                                        "unit": "x lower limit"
                                    }
                                ]
                            }
                        }
                    }
                ]
            },
            "logical_structure": {
                "condition": {
                    "exact_snippets": "liver metastases",
                    "criterion": "liver metastases",
                    "requirement": {
                        "requirement_type": "presence",
                        "expected_value": true
                    }
                },
                "then_criteria": {
                    "and_criteria": [
                        {
                            "exact_snippets": "AST (GOT) [aspartate aminotransferase] ... < 3 x lower limit (5 x lower limit in case of liver metastases)",
                            "criterion": "AST (GOT) [aspartate aminotransferase]",
                            "requirement": {
                                "requirement_type": "level",
                                "expected_value": {
                                    "comparisons": [
                                        {
                                            "operator": "<",
                                            "value": 5,
                                            "unit": "x lower limit"
                                        }
                                    ]
                                }
                            }
                        },
                        {
                            "exact_snippets": "ALT (GPT) [alanine transaminase] ... < 3 x lower limit (5 x lower limit in case of liver metastases)",
                            "criterion": "ALT (GPT) [alanine transaminase]",
                            "requirement": {
                                "requirement_type": "level",
                                "expected_value": {
                                    "comparisons": [
                                        {
                                            "operator": "<",
                                            "value": 5,
                                            "unit": "x lower limit"
                                        }
                                    ]
                                }
                            }
                        }
                    ]
                },
                "else_criteria": {
                    "and_criteria": [
                        {
                            "exact_snippets": "AST (GOT) [aspartate aminotransferase] ... < 3 x lower limit (5 x lower limit in case of liver metastases)",
                            "criterion": "AST (GOT) [aspartate aminotransferase]",
                            "requirement": {
                                "requirement_type": "level",
                                "expected_value": {
                                    "comparisons": [
                                        {
                                            "operator": "<",
                                            "value": 3,
                                            "unit": "x lower limit"
                                        }
                                    ]
                                }
                            }
                        },
                        {
                            "exact_snippets": "ALT (GPT) [alanine transaminase] ... < 3 x lower limit (5 x lower limit in case of liver metastases)",
                            "criterion": "ALT (GPT) [alanine transaminase]",
                            "requirement": {
                                "requirement_type": "level",
                                "expected_value": {
                                    "comparisons": [
                                        {
                                            "operator": "<",
                                            "value": 3,
                                            "unit": "x lower limit"
                                        }
                                    ]
                                }
                            }
                        }
                    ]
                }
            }
        },
        {
            "identified_line": {
                "line": "Healthy volunteers allowed",
                "criterions": [
                    {
                        "exact_snippets": "Healthy volunteers allowed",
                        "criterion": "volunteer health status",
                        "requirement": {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "Healthy volunteers allowed",
                        "criterion": "volunteer health status",
                        "requirement": {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "Must have minimum age of 18 Years",
                "criterions": [
                    {
                        "exact_snippets": "minimum age of 18 Years",
                        "criterion": "age",
                        "requirement": {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "minimum age of 18 Years",
                        "criterion": "age",
                        "requirement": {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "12. Adequate bone marrow function, liver and renal function:",
                "criterions": [
                    {
                        "exact_snippets": "Adequate bone marrow function",
                        "criterion": "bone marrow function",
                        "requirement": {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "adequate ... liver ... function",
                        "criterion": "liver function",
                        "requirement": {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "adequate ... renal function",
                        "criterion": "renal function",
                        "requirement": {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "Adequate bone marrow function",
                        "criterion": "bone marrow function",
                        "requirement": {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "adequate ... liver ... function",
                        "criterion": "liver function",
                        "requirement": {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "adequate ... renal function",
                        "criterion": "renal function",
                        "requirement": {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    }
                ]
            }
        }
    ],
    "exclusion_lines": [
        {
            "identified_line": {
                "line": "1. Live expectancy less than 3 months",
                "criterions": [
                    {
                        "exact_snippets": "Live expectancy less than 3 months",
                        "criterion": "life expectancy",
                        "requirement": {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "Live expectancy less than 3 months",
                        "criterion": "life expectancy",
                        "requirement": {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "2. Nasopharynx carcinoma",
                "criterions": [
                    {
                        "exact_snippets": "Nasopharynx carcinoma",
                        "criterion": "nasopharynx carcinoma",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    }
                ]
            },
            "logical_structure": {
                "not_criteria": {
                    "exact_snippets": "Nasopharynx carcinoma",
                    "criterion": "nasopharynx carcinoma",
                    "requirement": {
                        "requirement_type": "presence",
                        "expected_value": true
                    }
                }
            }
        },
        {
            "identified_line": {
                "line": "3. Anticancer treatment during the last 30 days prior to start of treatment, including systemic therapy, radiotherapy or major surgery",
                "criterions": [
                    {
                        "exact_snippets": "Anticancer treatment during the last 30 days prior to start of treatment",
                        "criterion": "anticancer treatment",
                        "requirement": {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 30,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    },
                    {
                        "exact_snippets": "systemic therapy",
                        "criterion": "systemic therapy",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "radiotherapy",
                        "criterion": "radiotherapy",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "major surgery",
                        "criterion": "major surgery",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    }
                ]
            },
            "logical_structure": {
                "or_criteria": [
                    {
                        "and_criteria": [
                            {
                                "exact_snippets": "Anticancer treatment during the last 30 days prior to start of treatment",
                                "criterion": "anticancer treatment",
                                "requirement": {
                                    "requirement_type": "time frame",
                                    "expected_value": {
                                        "comparisons": [
                                            {
                                                "operator": "<=",
                                                "value": 30,
                                                "unit": "days"
                                            }
                                        ]
                                    }
                                }
                            },
                            {
                                "exact_snippets": "systemic therapy",
                                "criterion": "systemic therapy",
                                "requirement": {
                                    "requirement_type": "presence",
                                    "expected_value": true
                                }
                            }
                        ]
                    },
                    {
                        "and_criteria": [
                            {
                                "exact_snippets": "Anticancer treatment during the last 30 days prior to start of treatment",
                                "criterion": "anticancer treatment",
                                "requirement": {
                                    "requirement_type": "time frame",
                                    "expected_value": {
                                        "comparisons": [
                                            {
                                                "operator": "<=",
                                                "value": 30,
                                                "unit": "days"
                                            }
                                        ]
                                    }
                                }
                            },
                            {
                                "exact_snippets": "radiotherapy",
                                "criterion": "radiotherapy",
                                "requirement": {
                                    "requirement_type": "presence",
                                    "expected_value": true
                                }
                            }
                        ]
                    },
                    {
                        "and_criteria": [
                            {
                                "exact_snippets": "Anticancer treatment during the last 30 days prior to start of treatment",
                                "criterion": "anticancer treatment",
                                "requirement": {
                                    "requirement_type": "time frame",
                                    "expected_value": {
                                        "comparisons": [
                                            {
                                                "operator": "<=",
                                                "value": 30,
                                                "unit": "days"
                                            }
                                        ]
                                    }
                                }
                            },
                            {
                                "exact_snippets": "major surgery",
                                "criterion": "major surgery",
                                "requirement": {
                                    "requirement_type": "presence",
                                    "expected_value": true
                                }
                            }
                        ]
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "4. Participation in a clinical trial within the last 30 days prior to study treatment",
                "criterions": [
                    {
                        "exact_snippets": "Participation in a clinical trial within the last 30 days",
                        "criterion": "participation in a clinical trial",
                        "requirement": {
                            "requirement_type": "time since last participation",
                            "expected_value": {
                                "operator": "<=",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "Participation in a clinical trial within the last 30 days",
                        "criterion": "participation in a clinical trial",
                        "requirement": {
                            "requirement_type": "time since last participation",
                            "expected_value": {
                                "operator": "<=",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "5. History of allogeneic tissue/solid organ transplant",
                "criterions": [
                    {
                        "exact_snippets": "History of allogeneic tissue/solid organ transplant",
                        "criterion": "allogeneic tissue/solid organ transplant",
                        "requirement": {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    }
                ]
            },
            "logical_structure": {
                "not_criteria": {
                    "exact_snippets": "History of allogeneic tissue/solid organ transplant",
                    "criterion": "allogeneic tissue/solid organ transplant",
                    "requirement": {
                        "requirement_type": "history",
                        "expected_value": true
                    }
                }
            }
        },
        {
            "identified_line": {
                "line": "6. History of pneumonitis that has required oral or i.v. steroids",
                "criterions": [
                    {
                        "exact_snippets": "History of pneumonitis that has required oral or i.v. steroids",
                        "criterion": "pneumonitis",
                        "requirement": {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "History of pneumonitis that has required oral or i.v. steroids",
                        "criterion": "pneumonitis",
                        "requirement": {
                            "requirement_type": "treatment",
                            "expected_value": [
                                "oral steroids",
                                "i.v. steroids"
                            ]
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "History of pneumonitis that has required oral or i.v. steroids",
                        "criterion": "pneumonitis",
                        "requirement": {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "History of pneumonitis that has required oral or i.v. steroids",
                        "criterion": "pneumonitis",
                        "requirement": {
                            "requirement_type": "treatment",
                            "expected_value": [
                                "oral steroids",
                                "i.v. steroids"
                            ]
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "7. Evidence of interstitial lung disease",
                "criterions": [
                    {
                        "exact_snippets": "Evidence of interstitial lung disease",
                        "criterion": "interstitial lung disease",
                        "requirement": {
                            "requirement_type": "evidence",
                            "expected_value": true
                        }
                    }
                ]
            },
            "logical_structure": {
                "not_criteria": {
                    "exact_snippets": "Evidence of interstitial lung disease",
                    "criterion": "interstitial lung disease",
                    "requirement": {
                        "requirement_type": "evidence",
                        "expected_value": true
                    }
                }
            }
        },
        {
            "identified_line": {
                "line": "9. Symptomatic acute cardiovascular or cerebrovascular disease",
                "criterions": [
                    {
                        "exact_snippets": "Symptomatic acute cardiovascular ... disease",
                        "criterion": "acute cardiovascular disease",
                        "requirement": {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "Symptomatic acute ... cerebrovascular disease",
                        "criterion": "acute cerebrovascular disease",
                        "requirement": {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    }
                ]
            },
            "logical_structure": {
                "or_criteria": [
                    {
                        "exact_snippets": "Symptomatic acute cardiovascular ... disease",
                        "criterion": "acute cardiovascular disease",
                        "requirement": {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "Symptomatic acute ... cerebrovascular disease",
                        "criterion": "acute cerebrovascular disease",
                        "requirement": {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "10. Known active HBV [hepatitis B virus], HCV [hepatitis C virus] or HIV infection",
                "criterions": [
                    {
                        "exact_snippets": "Known active HBV [hepatitis B virus]",
                        "criterion": "HBV infection",
                        "requirement": {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    },
                    {
                        "exact_snippets": "Known active ... HCV [hepatitis C virus]",
                        "criterion": "HCV infection",
                        "requirement": {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    },
                    {
                        "exact_snippets": "Known active ... HIV infection",
                        "criterion": "HIV infection",
                        "requirement": {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    }
                ]
            },
            "logical_structure": {
                "or_criteria": [
                    {
                        "exact_snippets": "Known active HBV [hepatitis B virus]",
                        "criterion": "HBV infection",
                        "requirement": {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    },
                    {
                        "exact_snippets": "Known active ... HCV [hepatitis C virus]",
                        "criterion": "HCV infection",
                        "requirement": {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    },
                    {
                        "exact_snippets": "Known active ... HIV infection",
                        "criterion": "HIV infection",
                        "requirement": {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "11. Has any other active infection requiring systemic therapy.",
                "criterions": [
                    {
                        "exact_snippets": "any other active infection requiring systemic therapy",
                        "criterion": "active infection",
                        "requirement": {
                            "requirement_type": "treatment",
                            "expected_value": "systemic therapy"
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "exact_snippets": "any other active infection requiring systemic therapy",
                        "criterion": "active infection",
                        "requirement": {
                            "requirement_type": "treatment",
                            "expected_value": "systemic therapy"
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "12. Patients with active tuberculosis",
                "criterions": [
                    {
                        "exact_snippets": "Patients with active tuberculosis",
                        "criterion": "tuberculosis",
                        "requirement": {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    }
                ]
            },
            "logical_structure": {
                "not_criteria": {
                    "exact_snippets": "Patients with active tuberculosis",
                    "criterion": "tuberculosis",
                    "requirement": {
                        "requirement_type": "activity",
                        "expected_value": "active"
                    }
                }
            }
        },
        {
            "identified_line": {
                "line": "13. Prior therapy with an anti-Programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-Programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor (TNFR) family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)",
                "criterions": [
                    {
                        "exact_snippets": "Prior therapy with an anti-Programmed cell death protein 1 (anti-PD-1)",
                        "criterion": "prior therapy with anti-PD-1",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "Prior therapy with ... anti-PD-L1",
                        "criterion": "prior therapy with anti-PD-L1",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "Prior therapy with ... anti-Programmed cell death-ligand 2 (anti-PD-L2)",
                        "criterion": "prior therapy with anti-PD-L2",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "Prior therapy with ... anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor (TNFR) family)",
                        "criterion": "prior therapy with anti-CD137",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "Prior therapy with ... anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)",
                        "criterion": "prior therapy with anti-CTLA-4",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    }
                ]
            },
            "logical_structure": {
                "or_criteria": [
                    {
                        "exact_snippets": "Prior therapy with an anti-Programmed cell death protein 1 (anti-PD-1)",
                        "criterion": "prior therapy with anti-PD-1",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "Prior therapy with ... anti-PD-L1",
                        "criterion": "prior therapy with anti-PD-L1",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "Prior therapy with ... anti-Programmed cell death-ligand 2 (anti-PD-L2)",
                        "criterion": "prior therapy with anti-PD-L2",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "Prior therapy with ... anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor (TNFR) family)",
                        "criterion": "prior therapy with anti-CD137",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "Prior therapy with ... anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)",
                        "criterion": "prior therapy with anti-CTLA-4",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "14. A diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.",
                "criterions": [
                    {
                        "exact_snippets": "A diagnosis of immunodeficiency",
                        "criterion": "immunodeficiency",
                        "requirement": {
                            "requirement_type": "diagnosis",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "patient is receiving chronic systemic steroid therapy",
                        "criterion": "chronic systemic steroid therapy",
                        "requirement": {
                            "requirement_type": "receiving",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment",
                        "criterion": "immunosuppressive therapy",
                        "requirement": {
                            "requirement_type": "receiving",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment",
                        "criterion": "immunosuppressive therapy",
                        "requirement": {
                            "requirement_type": "timeframe",
                            "expected_value": "within 7 days prior to the first dose of trial treatment"
                        }
                    }
                ]
            },
            "logical_structure": {
                "or_criteria": [
                    {
                        "and_criteria": [
                            {
                                "exact_snippets": "A diagnosis of immunodeficiency",
                                "criterion": "immunodeficiency",
                                "requirement": {
                                    "requirement_type": "diagnosis",
                                    "expected_value": true
                                }
                            }
                        ]
                    },
                    {
                        "and_criteria": [
                            {
                                "exact_snippets": "patient is receiving chronic systemic steroid therapy",
                                "criterion": "chronic systemic steroid therapy",
                                "requirement": {
                                    "requirement_type": "receiving",
                                    "expected_value": true
                                }
                            }
                        ]
                    },
                    {
                        "and_criteria": [
                            {
                                "exact_snippets": "any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment",
                                "criterion": "immunosuppressive therapy",
                                "requirement": {
                                    "requirement_type": "receiving",
                                    "expected_value": true
                                }
                            },
                            {
                                "exact_snippets": "any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment",
                                "criterion": "immunosuppressive therapy",
                                "requirement": {
                                    "requirement_type": "timeframe",
                                    "expected_value": "within 7 days prior to the first dose of trial treatment"
                                }
                            }
                        ]
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "15. Patient has had a prior monoclonal antibody, which does significantly interfere with the immune system or which does have a systemic therapeutic effect on the tumor within 4 weeks prior to randomization.",
                "criterions": [
                    {
                        "exact_snippets": "Patient has had a prior monoclonal antibody, which does significantly interfere with the immune system",
                        "criterion": "prior monoclonal antibody",
                        "requirement": {
                            "requirement_type": "interference with immune system",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "Patient has had a prior monoclonal antibody, ... which does have a systemic therapeutic effect on the tumor within 4 weeks prior to randomization",
                        "criterion": "prior monoclonal antibody",
                        "requirement": {
                            "requirement_type": "systemic therapeutic effect on tumor",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "Patient has had a prior monoclonal antibody, ... which does have a systemic therapeutic effect on the tumor within 4 weeks prior to randomization",
                        "criterion": "prior monoclonal antibody",
                        "requirement": {
                            "requirement_type": "time since administration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "and_criteria": [
                            {
                                "exact_snippets": "Patient has had a prior monoclonal antibody, which does significantly interfere with the immune system",
                                "criterion": "prior monoclonal antibody",
                                "requirement": {
                                    "requirement_type": "interference with immune system",
                                    "expected_value": true
                                }
                            },
                            {
                                "exact_snippets": "Patient has had a prior monoclonal antibody, ... which does have a systemic therapeutic effect on the tumor within 4 weeks prior to randomization",
                                "criterion": "prior monoclonal antibody",
                                "requirement": {
                                    "requirement_type": "systemic therapeutic effect on tumor",
                                    "expected_value": true
                                }
                            }
                        ]
                    },
                    {
                        "exact_snippets": "Patient has had a prior monoclonal antibody, ... which does have a systemic therapeutic effect on the tumor within 4 weeks prior to randomization",
                        "criterion": "prior monoclonal antibody",
                        "requirement": {
                            "requirement_type": "time since administration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "16. Patient has not recovered (i.e., ≤ Grade 1 or at baseline) from any toxicity due to agents administered more than 4 weeks earlier. [Subjects with ≤ Grade 2 neuropathy or alopecia are an exception to this criterion and may qualify for the study.]",
                "criterions": [
                    {
                        "exact_snippets": "Patient has not recovered ... from any toxicity",
                        "criterion": "recovery from toxicity",
                        "requirement": {
                            "requirement_type": "severity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "Grade"
                                    }
                                ]
                            }
                        }
                    },
                    {
                        "exact_snippets": "toxicity due to agents administered more than 4 weeks earlier",
                        "criterion": "time since administration of agents",
                        "requirement": {
                            "requirement_type": "time elapsed",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    },
                    {
                        "exact_snippets": "Subjects with ≤ Grade 2 neuropathy or alopecia are an exception",
                        "criterion": "neuropathy or alopecia",
                        "requirement": {
                            "requirement_type": "severity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "Grade"
                                    }
                                ]
                            }
                        }
                    }
                ]
            },
            "logical_structure": {
                "condition": {
                    "and_criteria": [
                        {
                            "and_criteria": [
                                {
                                    "exact_snippets": "Patient has not recovered ... from any toxicity",
                                    "criterion": "recovery from toxicity",
                                    "requirement": {
                                        "requirement_type": "severity",
                                        "expected_value": {
                                            "comparisons": [
                                                {
                                                    "operator": "<=",
                                                    "value": 1,
                                                    "unit": "Grade"
                                                }
                                            ]
                                        }
                                    }
                                },
                                {
                                    "exact_snippets": "toxicity due to agents administered more than 4 weeks earlier",
                                    "criterion": "time since administration of agents",
                                    "requirement": {
                                        "requirement_type": "time elapsed",
                                        "expected_value": {
                                            "comparisons": [
                                                {
                                                    "operator": ">",
                                                    "value": 4,
                                                    "unit": "weeks"
                                                }
                                            ]
                                        }
                                    }
                                }
                            ]
                        }
                    ]
                },
                "then_criteria": {
                    "not_criteria": {
                        "exact_snippets": "Subjects with ≤ Grade 2 neuropathy or alopecia are an exception",
                        "criterion": "neuropathy or alopecia",
                        "requirement": {
                            "requirement_type": "severity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "Grade"
                                    }
                                ]
                            }
                        }
                    }
                },
                "else_criteria": null
            }
        },
        {
            "identified_line": {
                "line": "17. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.",
                "criterions": [
                    {
                        "exact_snippets": "active autoimmune disease requiring systemic treatment within the past 3 months",
                        "criterion": "active autoimmune disease",
                        "requirement": {
                            "requirement_type": "treatment",
                            "expected_value": "systemic treatment within the past 3 months"
                        }
                    },
                    {
                        "exact_snippets": "documented history of clinically severe autoimmune disease",
                        "criterion": "clinically severe autoimmune disease",
                        "requirement": {
                            "requirement_type": "history",
                            "expected_value": "documented"
                        }
                    },
                    {
                        "exact_snippets": "syndrome that requires systemic steroids or immunosuppressive agents",
                        "criterion": "syndrome",
                        "requirement": {
                            "requirement_type": "treatment",
                            "expected_value": [
                                "systemic steroids",
                                "immunosuppressive agents"
                            ]
                        }
                    },
                    {
                        "exact_snippets": "Subjects with vitiligo or resolved childhood asthma/atopy would be an exception",
                        "criterion": "vitiligo or resolved childhood asthma/atopy",
                        "requirement": {
                            "requirement_type": "exception",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded",
                        "criterion": "intermittent use of bronchodilators or local steroid injections",
                        "requirement": {
                            "requirement_type": "exception",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded",
                        "criterion": "hypothyroidism stable on hormone replacement or Sjorgen's syndrome",
                        "requirement": {
                            "requirement_type": "exception",
                            "expected_value": true
                        }
                    }
                ]
            },
            "logical_structure": {
                "or_criteria": [
                    {
                        "and_criteria": [
                            {
                                "and_criteria": [
                                    {
                                        "not_criteria": {
                                            "exact_snippets": "Subjects with vitiligo or resolved childhood asthma/atopy would be an exception",
                                            "criterion": "vitiligo or resolved childhood asthma/atopy",
                                            "requirement": {
                                                "requirement_type": "exception",
                                                "expected_value": true
                                            }
                                        }
                                    },
                                    {
                                        "not_criteria": {
                                            "exact_snippets": "Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded",
                                            "criterion": "intermittent use of bronchodilators or local steroid injections",
                                            "requirement": {
                                                "requirement_type": "exception",
                                                "expected_value": true
                                            }
                                        }
                                    }
                                ]
                            },
                            {
                                "not_criteria": {
                                    "exact_snippets": "Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded",
                                    "criterion": "hypothyroidism stable on hormone replacement or Sjorgen's syndrome",
                                    "requirement": {
                                        "requirement_type": "exception",
                                        "expected_value": true
                                    }
                                }
                            }
                        ]
                    },
                    {
                        "exact_snippets": "active autoimmune disease requiring systemic treatment within the past 3 months",
                        "criterion": "active autoimmune disease",
                        "requirement": {
                            "requirement_type": "treatment",
                            "expected_value": "systemic treatment within the past 3 months"
                        }
                    },
                    {
                        "exact_snippets": "documented history of clinically severe autoimmune disease",
                        "criterion": "clinically severe autoimmune disease",
                        "requirement": {
                            "requirement_type": "history",
                            "expected_value": "documented"
                        }
                    },
                    {
                        "exact_snippets": "syndrome that requires systemic steroids or immunosuppressive agents",
                        "criterion": "syndrome",
                        "requirement": {
                            "requirement_type": "treatment",
                            "expected_value": [
                                "systemic steroids",
                                "immunosuppressive agents"
                            ]
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "18. Has received a live vaccine within 30 days prior to the first dose of trial treatment.",
                "criterions": [
                    {
                        "exact_snippets": "Has received a live vaccine within 30 days prior to the first dose of trial treatment.",
                        "criterion": "live vaccine",
                        "requirement": {
                            "requirement_type": "time since administration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    }
                ]
            },
            "logical_structure": {
                "not_criteria": {
                    "exact_snippets": "Has received a live vaccine within 30 days prior to the first dose of trial treatment.",
                    "criterion": "live vaccine",
                    "requirement": {
                        "requirement_type": "time since administration",
                        "expected_value": {
                            "operator": "<=",
                            "value": 30,
                            "unit": "days"
                        }
                    }
                }
            }
        },
        {
            "identified_line": {
                "line": "19. Has known hypersensitivity to methotrexate or pembrolizumab or any constituent of the products..",
                "criterions": [
                    {
                        "exact_snippets": "known hypersensitivity to methotrexate",
                        "criterion": "hypersensitivity to methotrexate",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "known hypersensitivity to ... pembrolizumab",
                        "criterion": "hypersensitivity to pembrolizumab",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "known hypersensitivity to ... any constituent of the products",
                        "criterion": "hypersensitivity to any constituent of the products",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    }
                ]
            },
            "logical_structure": {
                "or_criteria": [
                    {
                        "exact_snippets": "known hypersensitivity to methotrexate",
                        "criterion": "hypersensitivity to methotrexate",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "known hypersensitivity to ... pembrolizumab",
                        "criterion": "hypersensitivity to pembrolizumab",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "known hypersensitivity to ... any constituent of the products",
                        "criterion": "hypersensitivity to any constituent of the products",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "20. Other active malignancy requiring treatment",
                "criterions": [
                    {
                        "exact_snippets": "Other active malignancy requiring treatment",
                        "criterion": "active malignancy",
                        "requirement": {
                            "requirement_type": "treatment requirement",
                            "expected_value": true
                        }
                    }
                ]
            },
            "logical_structure": {
                "not_criteria": {
                    "exact_snippets": "Other active malignancy requiring treatment",
                    "criterion": "active malignancy",
                    "requirement": {
                        "requirement_type": "treatment requirement",
                        "expected_value": true
                    }
                }
            }
        },
        {
            "identified_line": {
                "line": "21. Lactating or pregnant women, women of child-bearing potential who do not agree to the usage of highly effective contraception methods (allowed methods of contraception, meaning methods with a rate of failure of less than 1% per year are combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), vasectomized partner, bilateral tubal occlusion, sexual abstinence. If an oral contraception is used, a barrier method of contraception (e.g. male condom, female condom, cervical cap, diaphragm, contraceptive sponge) has to be applied additionally). Women of childbearing potential must have a negative pregnancy test (serum β-hCG) at Screening.",
                "criterions": [
                    {
                        "exact_snippets": "Lactating or pregnant women",
                        "criterion": "lactation",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    },
                    {
                        "exact_snippets": "Lactating or pregnant women",
                        "criterion": "pregnancy",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    },
                    {
                        "exact_snippets": "women of child-bearing potential who do not agree to the usage of highly effective contraception methods",
                        "criterion": "agreement to use contraception",
                        "requirement": {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "Women of childbearing potential must have a negative pregnancy test (serum β-hCG) at Screening",
                        "criterion": "pregnancy test",
                        "requirement": {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "or_criteria": [
                            {
                                "exact_snippets": "Lactating or pregnant women",
                                "criterion": "lactation",
                                "requirement": {
                                    "requirement_type": "presence",
                                    "expected_value": false
                                }
                            },
                            {
                                "exact_snippets": "Lactating or pregnant women",
                                "criterion": "pregnancy",
                                "requirement": {
                                    "requirement_type": "presence",
                                    "expected_value": false
                                }
                            }
                        ]
                    },
                    {
                        "not_criteria": {
                            "exact_snippets": "women of child-bearing potential who do not agree to the usage of highly effective contraception methods",
                            "criterion": "agreement to use contraception",
                            "requirement": {
                                "requirement_type": "agreement",
                                "expected_value": true
                            }
                        }
                    },
                    {
                        "not_criteria": {
                            "exact_snippets": "Women of childbearing potential must have a negative pregnancy test (serum β-hCG) at Screening",
                            "criterion": "pregnancy test",
                            "requirement": {
                                "requirement_type": "result",
                                "expected_value": "negative"
                            }
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "22. Any psychiatric illness that would affect the patient's ability to understand the demands of the clinical trial",
                "criterions": [
                    {
                        "exact_snippets": "psychiatric illness that would affect the patient's ability to understand the demands of the clinical trial",
                        "criterion": "psychiatric illness",
                        "requirement": {
                            "requirement_type": "impact on understanding",
                            "expected_value": "affects ability to understand trial demands"
                        }
                    }
                ]
            },
            "logical_structure": {
                "not_criteria": {
                    "exact_snippets": "psychiatric illness that would affect the patient's ability to understand the demands of the clinical trial",
                    "criterion": "psychiatric illness",
                    "requirement": {
                        "requirement_type": "impact on understanding",
                        "expected_value": "affects ability to understand trial demands"
                    }
                }
            }
        },
        {
            "identified_line": {
                "line": "23. Patient has already been recruited in this trial (does not include screening failures)",
                "criterions": [
                    {
                        "exact_snippets": "Patient has already been recruited in this trial",
                        "criterion": "recruitment status",
                        "requirement": {
                            "requirement_type": "status",
                            "expected_value": "already recruited"
                        }
                    },
                    {
                        "exact_snippets": "does not include screening failures",
                        "criterion": "screening failure",
                        "requirement": {
                            "requirement_type": "inclusion",
                            "expected_value": false
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "not_criteria": {
                            "exact_snippets": "does not include screening failures",
                            "criterion": "screening failure",
                            "requirement": {
                                "requirement_type": "inclusion",
                                "expected_value": false
                            }
                        }
                    },
                    {
                        "exact_snippets": "Patient has already been recruited in this trial",
                        "criterion": "recruitment status",
                        "requirement": {
                            "requirement_type": "status",
                            "expected_value": "already recruited"
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "24. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.",
                "criterions": [
                    {
                        "exact_snippets": "Patient who has been incarcerated",
                        "criterion": "incarceration status",
                        "requirement": {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    },
                    {
                        "exact_snippets": "involuntarily institutionalized by court order or by the authorities",
                        "criterion": "involuntary institutionalization",
                        "requirement": {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    }
                ]
            },
            "logical_structure": {
                "or_criteria": [
                    {
                        "exact_snippets": "Patient who has been incarcerated",
                        "criterion": "incarceration status",
                        "requirement": {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    },
                    {
                        "exact_snippets": "involuntarily institutionalized by court order or by the authorities",
                        "criterion": "involuntary institutionalization",
                        "requirement": {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "25. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].",
                "criterions": [
                    {
                        "exact_snippets": "Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial",
                        "criterion": "ability to consent",
                        "requirement": {
                            "requirement_type": "understanding",
                            "expected_value": true
                        }
                    }
                ]
            },
            "logical_structure": {
                "not_criteria": {
                    "exact_snippets": "Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial",
                    "criterion": "ability to consent",
                    "requirement": {
                        "requirement_type": "understanding",
                        "expected_value": true
                    }
                }
            }
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "identified_line": {
                "line": "3. Histological or cytological confirmed recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) not amenable to local therapies",
                "criterions": [
                    {
                        "exact_snippets": "Histological or cytological confirmed",
                        "criterion": "confirmation method",
                        "requirement": {
                            "requirement_type": "method",
                            "expected_value": [
                                "histological",
                                "cytological"
                            ]
                        }
                    },
                    {
                        "exact_snippets": "recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC)",
                        "criterion": "squamous cell carcinoma of the head and neck",
                        "requirement": {
                            "requirement_type": "status",
                            "expected_value": [
                                "recurrent",
                                "metastatic"
                            ]
                        }
                    },
                    {
                        "exact_snippets": "not amenable to local therapies",
                        "criterion": "amenability to local therapies",
                        "requirement": {
                            "requirement_type": "amenability",
                            "expected_value": false
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "and_criteria": [
                            {
                                "or_criteria": [
                                    {
                                        "exact_snippets": "Histological or cytological confirmed",
                                        "criterion": "confirmation method",
                                        "requirement": {
                                            "requirement_type": "method",
                                            "expected_value": [
                                                "histological"
                                            ]
                                        }
                                    },
                                    {
                                        "exact_snippets": "Histological or cytological confirmed",
                                        "criterion": "confirmation method",
                                        "requirement": {
                                            "requirement_type": "method",
                                            "expected_value": [
                                                "cytological"
                                            ]
                                        }
                                    }
                                ]
                            },
                            {
                                "or_criteria": [
                                    {
                                        "exact_snippets": "recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC)",
                                        "criterion": "squamous cell carcinoma of the head and neck",
                                        "requirement": {
                                            "requirement_type": "status",
                                            "expected_value": [
                                                "recurrent"
                                            ]
                                        }
                                    },
                                    {
                                        "exact_snippets": "recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC)",
                                        "criterion": "squamous cell carcinoma of the head and neck",
                                        "requirement": {
                                            "requirement_type": "status",
                                            "expected_value": [
                                                "metastatic"
                                            ]
                                        }
                                    }
                                ]
                            }
                        ]
                    },
                    {
                        "exact_snippets": "not amenable to local therapies",
                        "criterion": "amenability to local therapies",
                        "requirement": {
                            "requirement_type": "amenability",
                            "expected_value": false
                        }
                    }
                ]
            }
        },
        {
            "identified_line": {
                "line": "4. Progressive disease at study entry",
                "criterions": [
                    {
                        "exact_snippets": "Progressive disease at study entry",
                        "criterion": "progressive disease",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    }
                ]
            },
            "logical_structure": {
                "exact_snippets": "failed",
                "criterion": "failed",
                "requirement": {
                    "requirement_type": "failed",
                    "expected_value": "failed"
                }
            }
        },
        {
            "identified_line": {
                "line": "5. At least 1 measurable lesion according to RECIST 1.1",
                "criterions": [
                    {
                        "exact_snippets": "At least 1 measurable lesion according to RECIST 1.1",
                        "criterion": "measurable lesion",
                        "requirement": {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        }
                    },
                    {
                        "exact_snippets": "At least 1 measurable lesion according to RECIST 1.1",
                        "criterion": "measurable lesion",
                        "requirement": {
                            "requirement_type": "measurement standard",
                            "expected_value": "RECIST 1.1"
                        }
                    }
                ]
            },
            "logical_structure": {
                "exact_snippets": "failed",
                "criterion": "failed",
                "requirement": {
                    "requirement_type": "failed",
                    "expected_value": "failed"
                }
            }
        },
        {
            "identified_line": {
                "line": "6. No previous systemic treatment for metastatic disease",
                "criterions": [
                    {
                        "exact_snippets": "No previous systemic treatment for metastatic disease",
                        "criterion": "previous systemic treatment for metastatic disease",
                        "requirement": {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    }
                ]
            },
            "logical_structure": {
                "exact_snippets": "failed",
                "criterion": "failed",
                "requirement": {
                    "requirement_type": "failed",
                    "expected_value": "failed"
                }
            }
        },
        {
            "identified_line": {
                "line": "13. Tumor block or 20 slides must be available at study inclusion for central pathology testing",
                "criterions": [
                    {
                        "exact_snippets": "Tumor block or 20 slides must be available",
                        "criterion": "tumor block or 20 slides",
                        "requirement": {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    },
                    {
                        "exact_snippets": "central pathology testing",
                        "criterion": "central pathology testing",
                        "requirement": {
                            "requirement_type": "purpose",
                            "expected_value": "study inclusion"
                        }
                    }
                ]
            },
            "logical_structure": {
                "and_criteria": [
                    {
                        "or_criteria": [
                            {
                                "exact_snippets": "Tumor block or 20 slides must be available",
                                "criterion": "tumor block",
                                "requirement": {
                                    "requirement_type": "availability",
                                    "expected_value": true
                                }
                            },
                            {
                                "exact_snippets": "Tumor block or 20 slides must be available",
                                "criterion": "20 slides",
                                "requirement": {
                                    "requirement_type": "availability",
                                    "expected_value": true
                                }
                            }
                        ]
                    },
                    {
                        "exact_snippets": "central pathology testing",
                        "criterion": "central pathology testing",
                        "requirement": {
                            "requirement_type": "purpose",
                            "expected_value": "study inclusion"
                        }
                    }
                ]
            }
        }
    ],
    "failed_exclusion": [
        {
            "identified_line": {
                "line": "8. Minor surgery ≤ 24 hours prior first dose of study treatment",
                "criterions": [
                    {
                        "exact_snippets": "Minor surgery ≤ 24 hours prior first dose of study treatment",
                        "criterion": "minor surgery",
                        "requirement": {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 24,
                                "unit": "hours"
                            }
                        }
                    }
                ]
            },
            "logical_structure": {
                "not_criteria": {
                    "exact_snippets": "Minor surgery \u0010 24 hours prior first dose of study treatment",
                    "criterion": "minor surgery",
                    "requirement": {
                        "requirement_type": "timing",
                        "expected_value": {
                            "operator": "<=",
                            "value": 24,
                            "unit": "hours"
                        }
                    }
                }
            }
        }
    ],
    "failed_miscellaneous": []
}