{
    "info": {
        "nct_id": "NCT03091491",
        "official_title": "Randomised Phase 2 Study of Nivolumab Versus Nivolumab and Ipilimumab Combination in EGFR Mutant Non-small Cell Lung Cancer",
        "inclusion_criteria": "i. Signed informed consent\n\nii. Male or female, 21 years or older\n\n* Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug\n* Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab\n* Women must not be breastfeeding\n* Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception\n* WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 milli-international units per millilitre (mIU/mL).\n* Women of childbearing potential (WOCBP) receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days.\n\niii. Advanced EGFR+ NSCLC\n\niv. Eastern Cooperative Oncology Group (ECOG) 0-2 performance status\n\nv. Progressed on one line of standard EGFR TKI and not more than one line of chemotherapy; 3rd generation EGFR TKI for patients with T790M mutation is allowed\n\n* A 14-day washout period is required for EGFR TKI for patients who received this as the last therapy before recruitment\n* A 28-day washout period is required for chemotherapy for patients who received this as the last therapy before recruitment. All drug-related toxicities should have returned to baseline with the exception of neuropathy, fatigue, and alopecia.\n\nvi. Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to randomization/registration\n\n* White Blood Cell (WBC) ≥ 2000/µL\n* Neutrophils ≥ 1000/µL\n* Platelets ≥ 100 x 10^3/µL\n* Hemoglobin > 9.0 g/dL\n* Serum creatinine ≤ 1.5 x Upper Limit of Normal (ULN) or creatinine clearance (CrCl) ≥ 30 mL/min (if using the Cockcroft-Gault formula below):\n* Aspartate Aminotransferase/ Alanine Aminotransferase (AST/ALT) ≤ 3 x ULN\n* Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)\n\nvii. Measurable disease, as defined by RECIST v1.1; Previously irradiated lesions can only be considered as measurable disease if disease progression has been unequivocally documented at that site since radiation.\n\nviii. Patients with a history of treated asymptomatic central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria:\n\n1. Measurable disease outside CNS\n2. No ongoing requirement for corticosteroids as therapy for CNS disease; anticonvulsants at a stable dose allowed\n3. No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization\n4. No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study\n\nix. Tumor sites amenable for CT-guided core biopsies or trucut biopsies\n\nx. Willing to undergo 2 biopsies and contribute research bloods for the study. Archived tissue that is less than 6 months old is acceptable as an alternative to biopsy at screening if a biopsy is not feasible; patients from arm A must be willing to undergo biopsy as baseline upon clear-cut disease progression and on-treatment repeat biopsy before they are allowed to cross over to receive ipilimumab in addition to nivolumab.\n\nxi. Patients with confirmed concomitant HBV infection that are eligible for inclusion must be treated with antiviral therapy prior to enrollment to ensure adequate viral suppression (HBV DNA < 2000 IU/mL), must remain on antiviral therapy for the study duration, and continue therapy for 6 months after the last dose of investigational product(s). Subjects with confirmed Hepatitis C (HCV) infection who are negative for HBsAg and positive for anti-HBc, are eligible but must be started on active antiviral therapy (for HBV) prior to their first dose of investigational product.\n\nxi. For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception and to continue its use for 90 days after the last dose of nivolumab\n\nxii. Women who are not postmenopausal (≥12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 24 hours prior to initiation of study drug\n\nxiii. Available for follow-up\nHealthy volunteers allowed\nMust have minimum age of 21 Years\nMust have maximum age of 99 Years",
        "exclusion_criteria": "i. Symptomatic brain or leptomeningeal metastases (patients who have treated stable brain or Leptomeningeal disease are eligible; there is no magnetic resonance imaging (MRI) evidence of progression for [lowest minimum is 4 weeks or more] after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration).\n\nii. Poor performance status of ECOG 3-4\n\niii. Tumour sites not amenable to CT-guided core biopsies or trucut biopsies; However waiver for this criterion can be given for selected patients on a case-by-case basis for patients with sites of disease that are technically difficult to access after discussion with interventional radiologist. Waivers are allowed for not more than 70 patients for this study in order to allow sufficient number of quality tumour biopsies for biomarker analysis in this study. Waivers would have to be approved by the Principal Investigator.\n\niv. Unwilling to undergo 2 biopsies and contribute research bloods for the study\n\nv. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins\n\nvi. Concurrent Autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.\n\nvii. Prior treatment with other anti-Programmed cell death protein 1 (anti-PD1) or anti-PDL1 or anti-CTLA4 therapies\n\nviii. Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (anti-TNF) agents) within 2 weeks prior to randomization\n\n1. Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study.\n2. Patients with history of allergic reaction to IV contrast requiring steroid pre-treatment should have baseline and subsequent tumor assessments done by MRI.\n3. The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.\n\nix. Active interstitial lung disease or history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan; History of radiation pneumonitis in the radiation field (fibrosis) is permitted.\n\nx. Active tuberculosis\n\nxi. Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)\n\nxii. Prior allogeneic bone marrow transplantation or solid organ transplant\n\nxiii. Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation that such a live attenuated vaccine will be required during the study\n\nxiv. Not available for follow-up and unlikely to be compliant with follow-up or protocol requirements",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "i. Signed informed consent",
            "criterions": [
                {
                    "exact_snippets": "Signed informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "ii. Male or female, 21 years or older",
            "criterions": [
                {
                    "exact_snippets": "Male or female",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "male",
                                "female"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "21 years or older",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 21,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential (WOCBP)",
                    "criterion": "women of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must use appropriate method(s) of contraception",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "WOCBP should use an adequate method to avoid pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug",
                    "criterion": "contraception duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "5 months after the last dose of investigational drug"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "negative serum or urine pregnancy test",
                    "criterion": "pregnancy test result",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "minimum sensitivity 25 IU/L or equivalent units of HCG",
                    "criterion": "pregnancy test sensitivity",
                    "requirements": [
                        {
                            "requirement_type": "sensitivity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 25,
                                "unit": "IU/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "within 24 hours prior to the start of nivolumab",
                    "criterion": "timing of pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 24 hours prior to the start of nivolumab"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women must not be breastfeeding",
            "criterions": [
                {
                    "exact_snippets": "Women must not be breastfeeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception",
            "criterions": [
                {
                    "exact_snippets": "Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year",
                    "criterion": "contraceptive method failure rate",
                    "requirements": [
                        {
                            "requirement_type": "failure rate",
                            "expected_value": {
                                "operator": "<",
                                "value": 1,
                                "unit": "% per year"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product",
                    "criterion": "contraception adherence period",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "=",
                                "value": 7,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "not of childbearing potential"
                        }
                    ]
                },
                {
                    "exact_snippets": "azoospermic men do not require contraception",
                    "criterion": "azoospermia",
                    "requirements": [
                        {
                            "requirement_type": "contraception requirement",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 milli-international units per millilitre (mIU/mL).",
            "criterions": [
                {
                    "exact_snippets": "female who has experienced menarche",
                    "criterion": "menarche",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "female who ... has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy)",
                    "criterion": "surgical sterilization",
                    "requirements": [
                        {
                            "requirement_type": "absence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "female who ... is not postmenopausal",
                    "criterion": "postmenopausal status",
                    "requirements": [
                        {
                            "requirement_type": "absence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "12 months of amenorrhea in a woman over 45",
                    "criterion": "amenorrhea",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 12,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "12 months of amenorrhea in a woman over 45",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">",
                                "value": 45,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "women under the age of 55",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<",
                                "value": 55,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "documented serum follicle stimulating hormone (FSH) level less than 40 milli-international units per millilitre (mIU/mL)",
                    "criterion": "serum follicle stimulating hormone (FSH) level",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<",
                                "value": 40,
                                "unit": "mIU/mL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of childbearing potential (WOCBP) receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days.",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential (WOCBP) receiving nivolumab",
                    "criterion": "women of childbearing potential receiving nivolumab",
                    "requirements": [
                        {
                            "requirement_type": "contraception adherence duration",
                            "expected_value": {
                                "operator": "=",
                                "value": 5,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Men receiving nivolumab and who are sexually active with WOCBP",
                    "criterion": "men receiving nivolumab and sexually active with WOCBP",
                    "requirements": [
                        {
                            "requirement_type": "contraception adherence duration",
                            "expected_value": {
                                "operator": "=",
                                "value": 7,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "iii. Advanced EGFR+ NSCLC",
            "criterions": [
                {
                    "exact_snippets": "Advanced EGFR+ NSCLC",
                    "criterion": "EGFR mutation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Advanced EGFR+ NSCLC",
                    "criterion": "NSCLC",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "advanced"
                        }
                    ]
                }
            ]
        },
        {
            "line": "iv. Eastern Cooperative Oncology Group (ECOG) 0-2 performance status",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) 0-2 performance status",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "v. Progressed on one line of standard EGFR TKI and not more than one line of chemotherapy; 3rd generation EGFR TKI for patients with T790M mutation is allowed",
            "criterions": [
                {
                    "exact_snippets": "Progressed on one line of standard EGFR TKI",
                    "criterion": "progression on standard EGFR TKI",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "=",
                                "value": 1,
                                "unit": "line"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "not more than one line of chemotherapy",
                    "criterion": "chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "line"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "3rd generation EGFR TKI for patients with T790M mutation is allowed",
                    "criterion": "3rd generation EGFR TKI",
                    "requirements": [
                        {
                            "requirement_type": "mutation",
                            "expected_value": "T790M"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* A 14-day washout period is required for EGFR TKI for patients who received this as the last therapy before recruitment",
            "criterions": [
                {
                    "exact_snippets": "14-day washout period is required for EGFR TKI",
                    "criterion": "EGFR TKI washout period",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patients who received this as the last therapy before recruitment",
                    "criterion": "last therapy before recruitment",
                    "requirements": [
                        {
                            "requirement_type": "therapy type",
                            "expected_value": "EGFR TKI"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* A 28-day washout period is required for chemotherapy for patients who received this as the last therapy before recruitment. All drug-related toxicities should have returned to baseline with the exception of neuropathy, fatigue, and alopecia.",
            "criterions": [
                {
                    "exact_snippets": "28-day washout period is required for chemotherapy",
                    "criterion": "chemotherapy washout period",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "All drug-related toxicities should have returned to baseline",
                    "criterion": "drug-related toxicities",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "returned to baseline"
                        }
                    ]
                },
                {
                    "exact_snippets": "with the exception of neuropathy, fatigue, and alopecia",
                    "criterion": "drug-related toxicities exceptions",
                    "requirements": [
                        {
                            "requirement_type": "conditions",
                            "expected_value": [
                                "neuropathy",
                                "fatigue",
                                "alopecia"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "vi. Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to randomization/registration",
            "criterions": [
                {
                    "exact_snippets": "Screening laboratory values must meet the following criteria",
                    "criterion": "screening laboratory values",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": "must meet the following criteria"
                        }
                    ]
                },
                {
                    "exact_snippets": "should be obtained within 14 days prior to randomization/registration",
                    "criterion": "screening laboratory values",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 14 days prior to randomization/registration"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* White Blood Cell (WBC) ≥ 2000/µL",
            "criterions": [
                {
                    "exact_snippets": "White Blood Cell (WBC) ≥ 2000/µL",
                    "criterion": "White Blood Cell (WBC) count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2000,
                                "unit": "µL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Neutrophils ≥ 1000/µL",
            "criterions": [
                {
                    "exact_snippets": "Neutrophils ≥ 1000/µL",
                    "criterion": "neutrophils",
                    "requirements": [
                        {
                            "requirement_type": "count",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1000,
                                "unit": "µL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelets ≥ 100 x 10^3/µL",
            "criterions": [
                {
                    "exact_snippets": "Platelets ≥ 100 x 10^3/µL",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100000,
                                "unit": "/µL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin > 9.0 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin > 9.0 g/dL",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 9.0,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Serum creatinine ≤ 1.5 x Upper Limit of Normal (ULN) or creatinine clearance (CrCl) ≥ 30 mL/min (if using the Cockcroft-Gault formula below):",
            "criterions": [
                {
                    "exact_snippets": "Serum creatinine ≤ 1.5 x Upper Limit of Normal (ULN)",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinine clearance (CrCl) ≥ 30 mL/min",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 30,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Aspartate Aminotransferase/ Alanine Aminotransferase (AST/ALT) ≤ 3 x ULN",
            "criterions": [
                {
                    "exact_snippets": "Aspartate Aminotransferase/ Alanine Aminotransferase (AST/ALT) ≤ 3 x ULN",
                    "criterion": "Aspartate Aminotransferase/ Alanine Aminotransferase (AST/ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)",
            "criterions": [
                {
                    "exact_snippets": "Total Bilirubin ≤ 1.5 x ULN",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Gilbert Syndrome ... total bilirubin < 3.0 mg/dL",
                    "criterion": "total bilirubin in subjects with Gilbert Syndrome",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 3.0,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "vii. Measurable disease, as defined by RECIST v1.1; Previously irradiated lesions can only be considered as measurable disease if disease progression has been unequivocally documented at that site since radiation.",
            "criterions": [
                {
                    "exact_snippets": "Measurable disease, as defined by RECIST v1.1",
                    "criterion": "measurable disease",
                    "requirements": [
                        {
                            "requirement_type": "definition",
                            "expected_value": "RECIST v1.1"
                        }
                    ]
                },
                {
                    "exact_snippets": "Previously irradiated lesions can only be considered as measurable disease if disease progression has been unequivocally documented at that site since radiation",
                    "criterion": "previously irradiated lesions",
                    "requirements": [
                        {
                            "requirement_type": "consideration as measurable disease",
                            "expected_value": "disease progression has been unequivocally documented at that site since radiation"
                        }
                    ]
                }
            ]
        },
        {
            "line": "viii. Patients with a history of treated asymptomatic central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria:",
            "criterions": [
                {
                    "exact_snippets": "history of treated asymptomatic central nervous system (CNS) metastases",
                    "criterion": "CNS metastases",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "treatment",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "symptoms",
                            "expected_value": "asymptomatic"
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Measurable disease outside CNS",
            "criterions": [
                {
                    "exact_snippets": "Measurable disease outside CNS",
                    "criterion": "disease",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "location",
                            "expected_value": "outside CNS"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. No ongoing requirement for corticosteroids as therapy for CNS disease; anticonvulsants at a stable dose allowed",
            "criterions": [
                {
                    "exact_snippets": "No ongoing requirement for corticosteroids as therapy for CNS disease",
                    "criterion": "corticosteroids requirement",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "anticonvulsants at a stable dose allowed",
                    "criterion": "anticonvulsants dose stability",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization",
            "criterions": [
                {
                    "exact_snippets": "No stereotactic radiation within 7 days",
                    "criterion": "stereotactic radiation",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 7,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "No ... whole-brain radiation within 14 days",
                    "criterion": "whole-brain radiation",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study",
            "criterions": [
                {
                    "exact_snippets": "No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study",
                    "criterion": "interim progression",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "ix. Tumor sites amenable for CT-guided core biopsies or trucut biopsies",
            "criterions": [
                {
                    "exact_snippets": "Tumor sites amenable for CT-guided core biopsies or trucut biopsies",
                    "criterion": "tumor sites",
                    "requirements": [
                        {
                            "requirement_type": "amenability",
                            "expected_value": [
                                "CT-guided core biopsies",
                                "trucut biopsies"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "x. Willing to undergo 2 biopsies and contribute research bloods for the study. Archived tissue that is less than 6 months old is acceptable as an alternative to biopsy at screening if a biopsy is not feasible; patients from arm A must be willing to undergo biopsy as baseline upon clear-cut disease progression and on-treatment repeat biopsy before they are allowed to cross over to receive ipilimumab in addition to nivolumab.",
            "criterions": [
                {
                    "exact_snippets": "Willing to undergo 2 biopsies",
                    "criterion": "willingness to undergo biopsies",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "contribute research bloods for the study",
                    "criterion": "willingness to contribute research bloods",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Archived tissue that is less than 6 months old is acceptable as an alternative to biopsy at screening",
                    "criterion": "archived tissue age",
                    "requirements": [
                        {
                            "requirement_type": "age",
                            "expected_value": {
                                "operator": "<",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patients from arm A must be willing to undergo biopsy as baseline upon clear-cut disease progression",
                    "criterion": "willingness to undergo biopsy upon disease progression",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "on-treatment repeat biopsy before they are allowed to cross over to receive ipilimumab in addition to nivolumab",
                    "criterion": "willingness to undergo on-treatment repeat biopsy",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "xi. Patients with confirmed concomitant HBV infection that are eligible for inclusion must be treated with antiviral therapy prior to enrollment to ensure adequate viral suppression (HBV DNA < 2000 IU/mL), must remain on antiviral therapy for the study duration, and continue therapy for 6 months after the last dose of investigational product(s). Subjects with confirmed Hepatitis C (HCV) infection who are negative for HBsAg and positive for anti-HBc, are eligible but must be started on active antiviral therapy (for HBV) prior to their first dose of investigational product.",
            "criterions": [
                {
                    "exact_snippets": "confirmed concomitant HBV infection",
                    "criterion": "HBV infection",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "treated with antiviral therapy prior to enrollment",
                    "criterion": "antiviral therapy for HBV",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "prior to enrollment"
                        }
                    ]
                },
                {
                    "exact_snippets": "adequate viral suppression (HBV DNA < 2000 IU/mL)",
                    "criterion": "HBV DNA level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 2000,
                                "unit": "IU/mL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "remain on antiviral therapy for the study duration",
                    "criterion": "antiviral therapy for HBV",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "study duration"
                        }
                    ]
                },
                {
                    "exact_snippets": "continue therapy for 6 months after the last dose of investigational product(s)",
                    "criterion": "antiviral therapy for HBV",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "6 months after last dose"
                        }
                    ]
                },
                {
                    "exact_snippets": "confirmed Hepatitis C (HCV) infection",
                    "criterion": "HCV infection",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "negative for HBsAg",
                    "criterion": "HBsAg status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "positive for anti-HBc",
                    "criterion": "anti-HBc status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "started on active antiviral therapy (for HBV) prior to their first dose of investigational product",
                    "criterion": "antiviral therapy for HBV",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "prior to first dose"
                        }
                    ]
                }
            ]
        },
        {
            "line": "xi. For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception and to continue its use for 90 days after the last dose of nivolumab",
            "criterions": [
                {
                    "exact_snippets": "female patients of childbearing potential",
                    "criterion": "female patients of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "male patients with partners of childbearing potential",
                    "criterion": "male patients with partners of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "agreement (by patient and/or partner) to use a highly effective form(s) of contraception",
                    "criterion": "use of contraception",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "to continue its use for 90 days after the last dose of nivolumab",
                    "criterion": "duration of contraception use",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 90,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "xii. Women who are not postmenopausal (≥12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 24 hours prior to initiation of study drug",
            "criterions": [
                {
                    "exact_snippets": "Women who are not postmenopausal (≥12 months of non-therapy-induced amenorrhea)",
                    "criterion": "postmenopausal status",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "months"
                            }
                        },
                        {
                            "requirement_type": "induction",
                            "expected_value": "non-therapy-induced"
                        }
                    ]
                },
                {
                    "exact_snippets": "surgically sterile",
                    "criterion": "surgical sterility",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must have a negative serum pregnancy test result within 24 hours prior to initiation of study drug",
                    "criterion": "serum pregnancy test result",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 24 hours prior to initiation of study drug"
                        }
                    ]
                }
            ]
        },
        {
            "line": "xiii. Available for follow-up",
            "criterions": [
                {
                    "exact_snippets": "Available for follow-up",
                    "criterion": "follow-up availability",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 21 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 21 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 21,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 99 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 99 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 99,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "i. Symptomatic brain or leptomeningeal metastases (patients who have treated stable brain or Leptomeningeal disease are eligible; there is no magnetic resonance imaging (MRI) evidence of progression for [lowest minimum is 4 weeks or more] after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration).",
            "criterions": [
                {
                    "exact_snippets": "Symptomatic brain or leptomeningeal metastases",
                    "criterion": "symptomatic brain or leptomeningeal metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "treated stable brain or Leptomeningeal disease",
                    "criterion": "treated stable brain or leptomeningeal disease",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "no magnetic resonance imaging (MRI) evidence of progression",
                    "criterion": "MRI evidence of progression",
                    "requirements": [
                        {
                            "requirement_type": "evidence of progression",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents)",
                    "criterion": "requirement for immunosuppressive doses of systemic corticosteroids",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "> 10 mg/day prednisone equivalents",
                    "criterion": "dose of systemic corticosteroids",
                    "requirements": [
                        {
                            "requirement_type": "dose",
                            "expected_value": {
                                "operator": ">",
                                "value": 10,
                                "unit": "mg/day prednisone equivalents"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "ii. Poor performance status of ECOG 3-4",
            "criterions": [
                {
                    "exact_snippets": "Poor performance status of ECOG 3-4",
                    "criterion": "performance status",
                    "requirements": [
                        {
                            "requirement_type": "ECOG score",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 3,
                                        "unit": "ECOG"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "ECOG"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "iii. Tumour sites not amenable to CT-guided core biopsies or trucut biopsies; However waiver for this criterion can be given for selected patients on a case-by-case basis for patients with sites of disease that are technically difficult to access after discussion with interventional radiologist. Waivers are allowed for not more than 70 patients for this study in order to allow sufficient number of quality tumour biopsies for biomarker analysis in this study. Waivers would have to be approved by the Principal Investigator.",
            "criterions": [
                {
                    "exact_snippets": "Tumour sites not amenable to CT-guided core biopsies or trucut biopsies",
                    "criterion": "tumour site amenability",
                    "requirements": [
                        {
                            "requirement_type": "amenability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "iv. Unwilling to undergo 2 biopsies and contribute research bloods for the study",
            "criterions": [
                {
                    "exact_snippets": "Unwilling to undergo 2 biopsies",
                    "criterion": "willingness to undergo biopsies",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Unwilling to ... contribute research bloods",
                    "criterion": "willingness to contribute research bloods",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "v. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins",
            "criterions": [
                {
                    "exact_snippets": "History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins",
                    "criterion": "severe allergic, anaphylactic, or other hypersensitivity reactions",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "chimeric or humanized antibodies or fusion proteins",
                    "criterion": "chimeric or humanized antibodies or fusion proteins",
                    "requirements": [
                        {
                            "requirement_type": "hypersensitivity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "vi. Concurrent Autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.",
            "criterions": [
                {
                    "exact_snippets": "Concurrent Autoimmune disease",
                    "criterion": "autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "vitiligo",
                    "criterion": "vitiligo",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "type I diabetes mellitus",
                    "criterion": "type I diabetes mellitus",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "residual hypothyroidism due to autoimmune condition only requiring hormone replacement",
                    "criterion": "residual hypothyroidism",
                    "requirements": [
                        {
                            "requirement_type": "cause",
                            "expected_value": "autoimmune condition"
                        },
                        {
                            "requirement_type": "treatment",
                            "expected_value": "hormone replacement"
                        }
                    ]
                },
                {
                    "exact_snippets": "psoriasis not requiring systemic treatment",
                    "criterion": "psoriasis",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "not requiring systemic treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "conditions not expected to recur in the absence of an external trigger",
                    "criterion": "conditions not expected to recur",
                    "requirements": [
                        {
                            "requirement_type": "trigger",
                            "expected_value": "absence of an external trigger"
                        }
                    ]
                }
            ]
        },
        {
            "line": "vii. Prior treatment with other anti-Programmed cell death protein 1 (anti-PD1) or anti-PDL1 or anti-CTLA4 therapies",
            "criterions": [
                {
                    "exact_snippets": "Prior treatment with other anti-Programmed cell death protein 1 (anti-PD1)",
                    "criterion": "prior treatment with anti-PD1",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with other ... anti-PDL1",
                    "criterion": "prior treatment with anti-PDL1",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with other ... anti-CTLA4 therapies",
                    "criterion": "prior treatment with anti-CTLA4",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "viii. Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (anti-TNF) agents) within 2 weeks prior to randomization",
            "criterions": [
                {
                    "exact_snippets": "Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (anti-TNF) agents) within 2 weeks prior to randomization",
                    "criterion": "systemic immunosuppressive medications",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study.",
            "criterions": [
                {
                    "exact_snippets": "Patients who have received acute, low-dose, systemic immunosuppressant medications",
                    "criterion": "acute, low-dose, systemic immunosuppressant medications",
                    "requirements": [
                        {
                            "requirement_type": "receipt",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Patients with history of allergic reaction to IV contrast requiring steroid pre-treatment should have baseline and subsequent tumor assessments done by MRI.",
            "criterions": [
                {
                    "exact_snippets": "history of allergic reaction to IV contrast",
                    "criterion": "allergic reaction to IV contrast",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "requiring steroid pre-treatment",
                    "criterion": "steroid pre-treatment",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.",
            "criterions": [
                {
                    "exact_snippets": "The use of inhaled corticosteroids for chronic obstructive pulmonary disease ... are allowed.",
                    "criterion": "inhaled corticosteroids",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "chronic obstructive pulmonary disease"
                        },
                        {
                            "requirement_type": "usage",
                            "expected_value": "allowed"
                        }
                    ]
                },
                {
                    "exact_snippets": "The use of ... mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension ... are allowed.",
                    "criterion": "mineralocorticoids",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "orthostatic hypotension"
                        },
                        {
                            "requirement_type": "usage",
                            "expected_value": "allowed"
                        }
                    ]
                },
                {
                    "exact_snippets": "The use of ... low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.",
                    "criterion": "low-dose supplemental corticosteroids",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "adrenocortical insufficiency"
                        },
                        {
                            "requirement_type": "usage",
                            "expected_value": "allowed"
                        }
                    ]
                }
            ]
        },
        {
            "line": "ix. Active interstitial lung disease or history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan; History of radiation pneumonitis in the radiation field (fibrosis) is permitted.",
            "criterions": [
                {
                    "exact_snippets": "Active interstitial lung disease",
                    "criterion": "interstitial lung disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of idiopathic pulmonary fibrosis",
                    "criterion": "idiopathic pulmonary fibrosis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "organizing pneumonia (e.g., bronchiolitis obliterans)",
                    "criterion": "organizing pneumonia",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "drug-induced pneumonitis",
                    "criterion": "drug-induced pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "idiopathic pneumonitis",
                    "criterion": "idiopathic pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "evidence of active pneumonitis on screening chest CT scan",
                    "criterion": "active pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History of radiation pneumonitis in the radiation field (fibrosis) is permitted",
                    "criterion": "radiation pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "x. Active tuberculosis",
            "criterions": [
                {
                    "exact_snippets": "Active tuberculosis",
                    "criterion": "tuberculosis",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "xi. Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)",
            "criterions": [
                {
                    "exact_snippets": "known history of testing positive for human immunodeficiency virus (HIV)",
                    "criterion": "HIV status",
                    "requirements": [
                        {
                            "requirement_type": "history of testing positive",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "known acquired immunodeficiency syndrome (AIDS)",
                    "criterion": "AIDS status",
                    "requirements": [
                        {
                            "requirement_type": "known",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "xii. Prior allogeneic bone marrow transplantation or solid organ transplant",
            "criterions": [
                {
                    "exact_snippets": "Prior allogeneic bone marrow transplantation",
                    "criterion": "allogeneic bone marrow transplantation",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "solid organ transplant",
                    "criterion": "solid organ transplant",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "xiii. Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation that such a live attenuated vaccine will be required during the study",
            "criterions": [
                {
                    "exact_snippets": "Administration of a live, attenuated vaccine within 4 weeks before randomization",
                    "criterion": "live attenuated vaccine administration",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "anticipation that such a live attenuated vaccine will be required during the study",
                    "criterion": "live attenuated vaccine requirement",
                    "requirements": [
                        {
                            "requirement_type": "anticipated requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "xiv. Not available for follow-up and unlikely to be compliant with follow-up or protocol requirements",
            "criterions": [
                {
                    "exact_snippets": "Not available for follow-up",
                    "criterion": "availability for follow-up",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "unlikely to be compliant with follow-up",
                    "criterion": "compliance with follow-up",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unlikely to be compliant with ... protocol requirements",
                    "criterion": "compliance with protocol requirements",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}