{
    "info": {
        "nct_id": "NCT03356860",
        "official_title": "A Phase IB/II Study of Durvalumab (MEDI4736) Combined With Dose-dense EC in a Neoadjuvant Setting for Patients With Locally Advanced Luminal B HER2(-) or Triple Negative Breast Cancers.",
        "inclusion_criteria": "* Written informed consent and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations\n* Female and male aged > 18 years at time of study entry.\n* Patient has T1-T4 any N, M0, operable breast cancer\n* Confirmed invasive ductal, lobular, mixed or medullary breast carcinoma\n* TNBC defined as negative oestrogen and progesterone receptors as per local laboratory testing and negative HER2 defined as negative ISH test or an IHC status of 0 or 1+ as per local laboratory testing\n* Luminal B HER2 negative BC defined as positive oestrogen and/or progesterone receptors, a negative HER2 defined as negative ISH test or an IHC status of 0 or 1+ as per local laboratory testing and a Ki67 > 14%.\n* World Health Organisation (WHO) performance status of 0 or 1\n* Adequate normal organ and marrow function as defined below:\n\n  1. Haemoglobin ≥ 9.0 g/dL\n  2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (> 1500 per mm3)\n  3. Platelet count ≥ 100 x 109/L (>100,000 per mm3)\n  4. Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).\n  5. AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit\n  6. Serum creatinine CL>40 mL/min\n* Normal cardiac function must be confirmed by ECG and cardiac function assessed by US imagery, radionucleotide ventriculography or MUGA, 4 weeks prior to randomization. Results must be above the normal limit of the institution\n* Women must either be postmenopausal or must have a negative serum pregnancy test 14 days upon study entry.\n* For a woman of childbearing potential, an effective method of birth control must be employed.\n* Men must use 2 effective contraceptive measures or male sterilization with female partners of childbearing potential or pregnant female partners, or they must remain abstinent during the treatment period and for at least 6 months after the last dose of the study treatment.\n* Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.\n* Subject accepts planned biological samples collection and their use for the trial propose.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Involvement in the planning and/or conduct of the study\n* Previous enrolment in the present study\n* Participation in another clinical study with an investigational product during the last 4 weeks\n* Patient has locally recurrent or metastatic invasive BC\n* History of another primary malignancy except for:\n\n  1. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug\n  2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease\n  3. Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ or BC in situ.\n* Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy, immunotherapy) or radiotherapy for current breast cancer disease\n* Whatever the indication, receipt of a last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 21 days prior to the first dose of study drug\n* Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab\n* Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1\n* Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid\n* Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from electrocardiograms (ECGs) using Fridericia's Correction\n* Known or suspected congestive heart failure (>NYHA I) and / or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, uncontrolled or poorly controlled arterial hypertension (i.e. BP >140 / 90 mm Hg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease.\n* Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.\n* Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)\n* History of primary immunodeficiency\n* History of allogeneic organ transplant\n* History of hypersensitivity to durvalumab or any excipient\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent\n* Subjects with uncontrolled seizures.\n* Known history of active tuberculosis\n* Anticipation that a live attenuated vaccine will be required during the period from 30 days prior to the first planned durvalumab administration (e.i. week 18 and week 14 after study entry for the phase Ib and phase II respectively) to 5 months of durvalumab discontinuation. Influenza vaccination (inactivated forms only but not live attenuated forms) should be given during influenza season only (approximately October to March).\n* Female subjects who are pregnant, breast-feeding or female patients of reproductive potential who are not employing an effective method of birth control\n* Men with female partners of childbearing potential or pregnant female partners who are not employing an effective method of birth control\n* Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Written informed consent and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations",
            "criterions": [
                {
                    "exact_snippets": "Written informed consent ... obtained from the subject",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject",
                    "criterion": "locally-required authorization",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Female and male aged > 18 years at time of study entry.",
            "criterions": [
                {
                    "exact_snippets": "Female and male",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "female",
                                "male"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "aged > 18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": ">",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient has T1-T4 any N, M0, operable breast cancer",
            "criterions": [
                {
                    "exact_snippets": "T1-T4",
                    "criterion": "tumor size",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 1,
                                        "unit": "T"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "T"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "any N",
                    "criterion": "lymph node involvement",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": "any"
                        }
                    ]
                },
                {
                    "exact_snippets": "M0",
                    "criterion": "distant metastasis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "operable breast cancer",
                    "criterion": "operability of breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "operability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Confirmed invasive ductal, lobular, mixed or medullary breast carcinoma",
            "criterions": [
                {
                    "exact_snippets": "Confirmed invasive ductal, lobular, mixed or medullary breast carcinoma",
                    "criterion": "breast carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "subtype",
                            "expected_value": [
                                "invasive ductal",
                                "lobular",
                                "mixed",
                                "medullary"
                            ]
                        },
                        {
                            "requirement_type": "confirmation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* TNBC defined as negative oestrogen and progesterone receptors as per local laboratory testing and negative HER2 defined as negative ISH test or an IHC status of 0 or 1+ as per local laboratory testing",
            "criterions": [
                {
                    "exact_snippets": "negative oestrogen and progesterone receptors",
                    "criterion": "oestrogen and progesterone receptors",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "negative HER2 defined as negative ISH test",
                    "criterion": "HER2 ISH test",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "negative HER2 defined as ... IHC status of 0 or 1+",
                    "criterion": "HER2 IHC status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "0",
                                "1+"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Luminal B HER2 negative BC defined as positive oestrogen and/or progesterone receptors, a negative HER2 defined as negative ISH test or an IHC status of 0 or 1+ as per local laboratory testing and a Ki67 > 14%.",
            "criterions": [
                {
                    "exact_snippets": "Luminal B HER2 negative BC",
                    "criterion": "breast cancer subtype",
                    "requirements": [
                        {
                            "requirement_type": "subtype",
                            "expected_value": "Luminal B HER2 negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "positive oestrogen and/or progesterone receptors",
                    "criterion": "hormone receptor status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "negative HER2 defined as negative ISH test or an IHC status of 0 or 1+",
                    "criterion": "HER2 status",
                    "requirements": [
                        {
                            "requirement_type": "ISH test",
                            "expected_value": "negative"
                        },
                        {
                            "requirement_type": "IHC status",
                            "expected_value": [
                                "0",
                                "1+"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Ki67 > 14%",
                    "criterion": "Ki67 index",
                    "requirements": [
                        {
                            "requirement_type": "percentage",
                            "expected_value": {
                                "operator": ">",
                                "value": 14,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* World Health Organisation (WHO) performance status of 0 or 1",
            "criterions": [
                {
                    "exact_snippets": "World Health Organisation (WHO) performance status of 0 or 1",
                    "criterion": "WHO performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate normal organ and marrow function as defined below:",
            "criterions": [
                {
                    "exact_snippets": "Adequate normal organ and marrow function",
                    "criterion": "organ and marrow function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": "normal"
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Haemoglobin ≥ 9.0 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Haemoglobin ≥ 9.0 g/dL",
                    "criterion": "haemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9.0,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (> 1500 per mm3)",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (> 1500 per mm3)",
                    "criterion": "absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 1.5,
                                        "unit": "x 10^9/L"
                                    },
                                    {
                                        "operator": ">",
                                        "value": 1500,
                                        "unit": "per mm3"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Platelet count ≥ 100 x 109/L (>100,000 per mm3)",
            "criterions": [
                {
                    "exact_snippets": "Platelet count ≥ 100 x 109/L (>100,000 per mm3)",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).",
            "criterions": [
                {
                    "exact_snippets": "Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).",
                    "criterion": "serum bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x institutional upper limit of normal (ULN)"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit",
            "criterions": [
                {
                    "exact_snippets": "AST (SGOT) ... ≤ 2.5 x institutional upper limit",
                    "criterion": "AST (SGOT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "x institutional upper limit"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ALT (SGPT) ≤ 2.5 x institutional upper limit",
                    "criterion": "ALT (SGPT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "x institutional upper limit"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Serum creatinine CL>40 mL/min",
            "criterions": [
                {
                    "exact_snippets": "Serum creatinine CL>40 mL/min",
                    "criterion": "serum creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 40,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Normal cardiac function must be confirmed by ECG and cardiac function assessed by US imagery, radionucleotide ventriculography or MUGA, 4 weeks prior to randomization. Results must be above the normal limit of the institution",
            "criterions": [
                {
                    "exact_snippets": "Normal cardiac function must be confirmed by ECG",
                    "criterion": "cardiac function",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "ECG"
                        }
                    ]
                },
                {
                    "exact_snippets": "cardiac function assessed by US imagery, radionucleotide ventriculography or MUGA",
                    "criterion": "cardiac function",
                    "requirements": [
                        {
                            "requirement_type": "assessment methods",
                            "expected_value": [
                                "US imagery",
                                "radionucleotide ventriculography",
                                "MUGA"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "4 weeks prior to randomization",
                    "criterion": "assessment timing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "4 weeks prior to randomization"
                        }
                    ]
                },
                {
                    "exact_snippets": "Results must be above the normal limit of the institution",
                    "criterion": "cardiac function results",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": "> normal limit of the institution"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women must either be postmenopausal or must have a negative serum pregnancy test 14 days upon study entry.",
            "criterions": [
                {
                    "exact_snippets": "Women must either be postmenopausal",
                    "criterion": "menopausal status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "postmenopausal"
                        }
                    ]
                },
                {
                    "exact_snippets": "must have a negative serum pregnancy test 14 days upon study entry",
                    "criterion": "serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "14 days upon study entry"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* For a woman of childbearing potential, an effective method of birth control must be employed.",
            "criterions": [
                {
                    "exact_snippets": "woman of childbearing potential",
                    "criterion": "woman of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "effective method of birth control must be employed",
                    "criterion": "birth control method",
                    "requirements": [
                        {
                            "requirement_type": "effectiveness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Men must use 2 effective contraceptive measures or male sterilization with female partners of childbearing potential or pregnant female partners, or they must remain abstinent during the treatment period and for at least 6 months after the last dose of the study treatment.",
            "criterions": [
                {
                    "exact_snippets": "Men must use 2 effective contraceptive measures",
                    "criterion": "contraceptive measures",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": ">= 2"
                        }
                    ]
                },
                {
                    "exact_snippets": "male sterilization",
                    "criterion": "sterilization",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "remain abstinent",
                    "criterion": "abstinence",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "during the treatment period and for at least 6 months after the last dose of the study treatment",
                    "criterion": "duration of contraceptive measures or abstinence",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "during the treatment period and for at least 6 months after the last dose of the study treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.",
            "criterions": [
                {
                    "exact_snippets": "Subject is willing and able to comply with the protocol",
                    "criterion": "compliance with protocol",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "undergoing treatment",
                    "criterion": "undergoing treatment",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "scheduled visits and examinations",
                    "criterion": "scheduled visits and examinations",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "including follow up",
                    "criterion": "follow up",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Subject accepts planned biological samples collection and their use for the trial propose.",
            "criterions": [
                {
                    "exact_snippets": "Subject accepts planned biological samples collection",
                    "criterion": "biological samples collection",
                    "requirements": [
                        {
                            "requirement_type": "acceptance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "their use for the trial propose",
                    "criterion": "use of biological samples",
                    "requirements": [
                        {
                            "requirement_type": "acceptance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Involvement in the planning and/or conduct of the study",
            "criterions": [
                {
                    "exact_snippets": "Involvement in the planning and/or conduct of the study",
                    "criterion": "involvement in study",
                    "requirements": [
                        {
                            "requirement_type": "participation",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Previous enrolment in the present study",
            "criterions": [
                {
                    "exact_snippets": "Previous enrolment in the present study",
                    "criterion": "previous enrolment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participation in another clinical study with an investigational product during the last 4 weeks",
            "criterions": [
                {
                    "exact_snippets": "Participation in another clinical study with an investigational product during the last 4 weeks",
                    "criterion": "participation in another clinical study",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient has locally recurrent or metastatic invasive BC",
            "criterions": [
                {
                    "exact_snippets": "locally recurrent or metastatic invasive BC",
                    "criterion": "breast cancer (BC)",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "locally recurrent",
                                "metastatic"
                            ]
                        },
                        {
                            "requirement_type": "invasiveness",
                            "expected_value": "invasive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of another primary malignancy except for:",
            "criterions": [
                {
                    "exact_snippets": "History of another primary malignancy",
                    "criterion": "history of another primary malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug",
            "criterions": [
                {
                    "exact_snippets": "Malignancy treated with curative intent",
                    "criterion": "malignancy treatment intent",
                    "requirements": [
                        {
                            "requirement_type": "intent",
                            "expected_value": "curative"
                        }
                    ]
                },
                {
                    "exact_snippets": "no known active disease ≥5 years before the first dose of study drug",
                    "criterion": "active disease status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 5,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease",
            "criterions": [
                {
                    "exact_snippets": "Adequately treated non-melanoma skin cancer",
                    "criterion": "non-melanoma skin cancer",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "adequately treated"
                        }
                    ]
                },
                {
                    "exact_snippets": "lentigo maligna without evidence of disease",
                    "criterion": "lentigo maligna",
                    "requirements": [
                        {
                            "requirement_type": "disease evidence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ or BC in situ.",
            "criterions": [
                {
                    "exact_snippets": "Adequately treated carcinoma in situ",
                    "criterion": "carcinoma in situ",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "adequately treated"
                        }
                    ]
                },
                {
                    "exact_snippets": "without evidence of disease",
                    "criterion": "evidence of disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy, immunotherapy) or radiotherapy for current breast cancer disease",
            "criterions": [
                {
                    "exact_snippets": "Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy, immunotherapy)",
                    "criterion": "systemic therapy for current breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patient has received any ... radiotherapy for current breast cancer disease",
                    "criterion": "radiotherapy for current breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Whatever the indication, receipt of a last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 21 days prior to the first dose of study drug",
            "criterions": [
                {
                    "exact_snippets": "receipt of a last dose of anti-cancer therapy ... ≤ 21 days prior to the first dose of study drug",
                    "criterion": "time since last anti-cancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "time interval",
                            "expected_value": {
                                "operator": "<=",
                                "value": 21,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab",
            "criterions": [
                {
                    "exact_snippets": "Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab",
                    "criterion": "previous treatment with PD1 or PD-L1 inhibitor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1",
            "criterions": [
                {
                    "exact_snippets": "Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent",
                    "criterion": "prior immune-related adverse event (irAE)",
                    "requirements": [
                        {
                            "requirement_type": "grade",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "Grade"
                            }
                        },
                        {
                            "requirement_type": "treatment context",
                            "expected_value": "while receiving any previous immunotherapy agent"
                        }
                    ]
                },
                {
                    "exact_snippets": "any unresolved irAE >Grade 1",
                    "criterion": "unresolved immune-related adverse event (irAE)",
                    "requirements": [
                        {
                            "requirement_type": "grade",
                            "expected_value": {
                                "operator": ">",
                                "value": 1,
                                "unit": "Grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid",
            "criterions": [
                {
                    "exact_snippets": "Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab",
                    "criterion": "use of immunosuppressive medication",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 28 days before the first dose of durvalumab"
                        }
                    ]
                },
                {
                    "exact_snippets": "exceptions of intranasal and inhaled corticosteroids",
                    "criterion": "use of intranasal and inhaled corticosteroids",
                    "requirements": [
                        {
                            "requirement_type": "exception",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "exceptions of ... systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid",
                    "criterion": "use of systemic corticosteroids",
                    "requirements": [
                        {
                            "requirement_type": "dose",
                            "expected_value": {
                                "operator": "<=",
                                "value": 10,
                                "unit": "mg/day of prednisone or equivalent"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from electrocardiograms (ECGs) using Fridericia's Correction",
            "criterions": [
                {
                    "exact_snippets": "Mean QT interval corrected for heart rate (QTc) ≥470 ms",
                    "criterion": "QTc interval",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 470,
                                "unit": "ms"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known or suspected congestive heart failure (>NYHA I) and / or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, uncontrolled or poorly controlled arterial hypertension (i.e. BP >140 / 90 mm Hg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease.",
            "criterions": [
                {
                    "exact_snippets": "Known or suspected congestive heart failure (>NYHA I)",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 1,
                                "unit": "NYHA"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "coronary heart disease",
                    "criterion": "coronary heart disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "angina pectoris requiring antianginal medication",
                    "criterion": "angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "antianginal medication"
                        }
                    ]
                },
                {
                    "exact_snippets": "previous history of myocardial infarction",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "evidence of transmural infarction on ECG",
                    "criterion": "transmural infarction",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": "ECG"
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled or poorly controlled arterial hypertension (i.e. BP >140 / 90 mm Hg under treatment with two antihypertensive drugs)",
                    "criterion": "arterial hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled or poorly controlled"
                        },
                        {
                            "requirement_type": "blood pressure",
                            "expected_value": {
                                "operator": ">",
                                "value": 140,
                                "unit": "mm Hg"
                            }
                        },
                        {
                            "requirement_type": "blood pressure",
                            "expected_value": {
                                "operator": ">",
                                "value": 90,
                                "unit": "mm Hg"
                            }
                        },
                        {
                            "requirement_type": "treatment",
                            "expected_value": "two antihypertensive drugs"
                        }
                    ]
                },
                {
                    "exact_snippets": "rhythm abnormalities requiring permanent treatment",
                    "criterion": "rhythm abnormalities",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "permanent"
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically significant valvular heart disease",
                    "criterion": "valvular heart disease",
                    "requirements": [
                        {
                            "requirement_type": "clinical significance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.",
            "criterions": [
                {
                    "exact_snippets": "Active or prior documented autoimmune disease within the past 2 years",
                    "criterion": "autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within the past 2 years"
                        }
                    ]
                },
                {
                    "exact_snippets": "Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded",
                    "criterion": "autoimmune disease exceptions",
                    "requirements": [
                        {
                            "requirement_type": "exceptions",
                            "expected_value": [
                                "vitiligo",
                                "Grave's disease",
                                "psoriasis not requiring systemic treatment"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)",
            "criterions": [
                {
                    "exact_snippets": "Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)",
                    "criterion": "inflammatory bowel disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of primary immunodeficiency",
            "criterions": [
                {
                    "exact_snippets": "History of primary immunodeficiency",
                    "criterion": "primary immunodeficiency",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of allogeneic organ transplant",
            "criterions": [
                {
                    "exact_snippets": "History of allogeneic organ transplant",
                    "criterion": "allogeneic organ transplant",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of hypersensitivity to durvalumab or any excipient",
            "criterions": [
                {
                    "exact_snippets": "History of hypersensitivity to durvalumab",
                    "criterion": "hypersensitivity to durvalumab",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity to ... any excipient",
                    "criterion": "hypersensitivity to any excipient",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection",
                    "criterion": "intercurrent illness",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "symptomatic congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled hypertension",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable angina pectoris",
                    "criterion": "angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "cardiac arrhythmia",
                    "criterion": "cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active peptic ulcer disease or gastritis",
                    "criterion": "peptic ulcer disease or gastritis",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active bleeding diatheses",
                    "criterion": "bleeding diatheses",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV)",
                    "criterion": "hepatitis B, hepatitis C or HIV",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent",
                    "criterion": "psychiatric illness/social situations",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance or consent",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Subjects with uncontrolled seizures.",
            "criterions": [
                {
                    "exact_snippets": "uncontrolled seizures",
                    "criterion": "seizures",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known history of active tuberculosis",
            "criterions": [
                {
                    "exact_snippets": "Known history of active tuberculosis",
                    "criterion": "active tuberculosis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Anticipation that a live attenuated vaccine will be required during the period from 30 days prior to the first planned durvalumab administration (e.i. week 18 and week 14 after study entry for the phase Ib and phase II respectively) to 5 months of durvalumab discontinuation. Influenza vaccination (inactivated forms only but not live attenuated forms) should be given during influenza season only (approximately October to March).",
            "criterions": [
                {
                    "exact_snippets": "Anticipation that a live attenuated vaccine will be required during the period from 30 days prior to the first planned durvalumab administration ... to 5 months of durvalumab discontinuation.",
                    "criterion": "live attenuated vaccine requirement",
                    "requirements": [
                        {
                            "requirement_type": "anticipation",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Influenza vaccination (inactivated forms only but not live attenuated forms) should be given during influenza season only (approximately October to March).",
                    "criterion": "influenza vaccination",
                    "requirements": [
                        {
                            "requirement_type": "form",
                            "expected_value": [
                                "inactivated"
                            ]
                        },
                        {
                            "requirement_type": "season",
                            "expected_value": "October to March"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Female subjects who are pregnant, breast-feeding or female patients of reproductive potential who are not employing an effective method of birth control",
            "criterions": [
                {
                    "exact_snippets": "Female subjects who are pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breast-feeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "female patients of reproductive potential",
                    "criterion": "reproductive potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "not employing an effective method of birth control",
                    "criterion": "birth control method",
                    "requirements": [
                        {
                            "requirement_type": "effectiveness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Men with female partners of childbearing potential or pregnant female partners who are not employing an effective method of birth control",
            "criterions": [
                {
                    "exact_snippets": "Men with female partners of childbearing potential",
                    "criterion": "female partner's childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "potential",
                            "expected_value": "childbearing"
                        }
                    ]
                },
                {
                    "exact_snippets": "Men with ... pregnant female partners",
                    "criterion": "female partner's pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "pregnant"
                        }
                    ]
                },
                {
                    "exact_snippets": "not employing an effective method of birth control",
                    "criterion": "use of birth control",
                    "requirements": [
                        {
                            "requirement_type": "employment",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results",
            "criterions": [
                {
                    "exact_snippets": "Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results",
                    "criterion": "condition interfering with study",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}