{
    "info": {
        "nct_id": "NCT02431559",
        "official_title": "Phase 1/2 Study of Chemoimmunotherapy With Toll-like Receptor 8 Agonist Motolimod (VTX-2337) + Anti-PD-L1 Antibody MEDI4736 in Subjects With Recurrent, Platinum-Resistant Ovarian Cancer for Whom Pegylated Liposomal Doxorubicin is Indicated",
        "inclusion_criteria": "1. Subjects must have had recurrent or persistent platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with measurable disease (as defined by the Response Evaluation Criteria in Solid Tumors [RECIST] 1.1.) after first or second line platinum-based chemotherapy, for which treatment with PLD was indicated. Platinum-based therapy was defined as treatment with carboplatin, cisplatin or another organoplatinum compound. Platinum-resistant was defined as having a platinum-free interval of < 12 months after first- or second-line platinum-based chemotherapy, or having disease progression while receiving second-line platinum-based chemotherapy.\n\n   Subjects were allowed to have received, but were not required to have received:\n   * one additional cytotoxic regimen and/or poly adenosine diphosphate-ribose polymerase inhibitor for management of recurrent or persistent disease.\n   * biologic therapy (e.g., bevacizumab) as part of their primary treatment regimen or part of their treatment for management of recurrent or persistent disease.\n2. Histologic documentation of the original primary tumor.\n3. Documented radiographic disease progression < 12 months after the last dose of first- or second-line platinum-based chemotherapy.\n4. Subjects in Phase 2 must have had disease amenable to biopsy and must have been willing to undergo pre- and post-treatment tumor biopsies. Optional for Phase 1.\n\n   Note: archival tissue was requested for all subjects preferably from primary tumor site prior to cancer treatment; however, archival tissue was not a requirement for study entry.\n5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n6. Laboratory parameters for vital functions should have been in the normal range. Laboratory abnormalities that were not clinically significant were generally permitted, except for the following laboratory parameters, which must have been within the ranges specified, regardless of clinical significance:\n\n   * Hemoglobin: ≥ 9 g/dL\n   * Neutrophil count: ≥ 1.5 x 10^9/L\n   * Platelet count: ≥ 100,000/mm^3\n   * Serum creatinine: ≤ 1.5 x institutional upper limit of normal (ULN), or creatinine clearance ≥ 50 mL/min (by Cockcroft-Gault formula)\n   * Serum bilirubin: ≤ 1.2 mg/dL\n   * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT): ≤ 2.5 x ULN\n   * Alkaline phosphatase: ≤ 2.5 x ULN\n7. Age ≥18 years.\n8. Able and willing to give valid written informed consent.\n9. Body weight > 30 kg.\nHealthy volunteers allowed\nMust be FEMALE\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Prior exposure to doxorubicin, PLD or any other anthracycline, motolimod and other toll-like receptor agonists, durvalumab or checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1)/anti-programmed cell death ligand-1 (PD-L1) antibodies.\n2. Subjects with platinum-refractory disease, defined as disease progression while receiving first line platinum-based therapy.\n3. Clinically significant persistent immune-related adverse events following prior therapy.\n4. Subjects with history or evidence upon physical examination of central nervous system disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or, within 6 months prior to Day 1 of this study, history of cerebrovascular accident (stroke), transient ischemic attack or subarachnoid hemorrhage.\n5. Subjects with clinically significant cardiovascular disease. This included:\n\n   1. Resistant hypertension.\n   2. Myocardial infarction or unstable angina within 6 months prior to Day 1 of the study.\n   3. History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications, except for atrial fibrillation that is well controlled with anti-arrhythmic medication.\n   4. Baseline ejection fraction ≤ 50% as assessed by echocardiogram or multiple-gated acquisition.\n   5. New York Heart Association Class II or higher congestive heart failure.\n   6. Grade 2 or higher peripheral ischemia, except for brief (< 24 hours) episodes of ischemia managed non-surgically and without permanent deficit.\n6. History of pneumonitis or interstitial lung disease.\n7. Active, suspected or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, Wegner's granulomatosis, active Hashimoto's thyroiditis, rheumatoid arthritis, lupus, scleroderma and its variants, multiple sclerosis, myasthenia gravis). 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 were permitted.\n8. Other malignancy within 2 years prior to Day 1 of the study, except for those treated with surgical intervention only.\n9. Subjects with clinical symptoms or signs of gastrointestinal obstruction and/or who required drainage gastrostomy tube and/or parenteral hydration or nutrition.\n10. Known immunodeficiency or human immunodeficiency virus, Hepatitis B or Hepatitis C positivity.\n11. History of severe allergic reactions to any unknown allergens or components of the study drugs.\n12. Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).\n13. Prior treatment in any other interventional clinical trial within 4 weeks prior to Day 1 of the study.\n14. Mental impairment that may have compromised compliance with the requirements of the study.\n15. Lack of availability for immunological and clinical follow-up assessment.\n16. Women of childbearing potential who were found to be pregnant as evidenced by positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) or nursing. NOTE: Pregnancy tests were not required for subjects who were not of childbearing potential as defined in #17.\n17. Female subjects of childbearing potential who were sexually active with a nonsterilized male partner must have used at least one highly effective method of contraception from screening, and must have agreed to continue using such precautions for 90 days after the final dose of investigational product (durvalumab). Male partners of a female subject must have used male condom plus spermicide throughout this period (from screening and for 90 days after subject's receipt of the final dose of investigational product). Cessation of birth control after this point should have been discussed with a responsible physician. Not engaging in sexual activity for the total duration of the trial and the drug washout period was an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method were not acceptable methods of birth control.\n\n    Female subjects should have refrained from breastfeeding throughout the period described above.\n\n    NOTE: For the standard of care, PLD (Doxil®, Caelyx®), the package insert advises females of reproductive potential to use effective contraception during and for 6 months after last treatment with the drug. Therefore, all subjects of childbearing potential on this study should have continued contraception use for 6 months after the last PLD administration.\n\n    Females of childbearing potential were defined as those who were not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or post-menopausal.\n\n    Females were considered post-menopausal if they had been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements applied:\n    * Females < 50 years of age were considered post-menopausal if they had been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they had luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).\n    * Females ≥ 50 years of age were considered post-menopausal if they had been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).\n\n    A highly effective method of contraception was defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Note that some contraception methods were not considered highly effective (e.g., male or female condom with or without spermicide; female cap, diaphragm, or sponge with or without spermicide; non-copper containing intrauterine device; progestogen-only oral hormonal contraceptive pills where inhibition of ovulation is not the primary mode of action [excluding Cerazette/desogestrel which is considered highly effective]; and triphasic combined oral contraceptive pills).\n18. Any condition that, in the clinical judgment of the treating physician, was likely to prevent the subject from complying with any aspect of the protocol or that may have put the subject at unacceptable risk.\n19. Subjects must not have donated blood while on study and for at least 90 days following the last durvalumab treatment.\n20. History of allogeneic organ transplant.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Subjects must have had recurrent or persistent platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with measurable disease (as defined by the Response Evaluation Criteria in Solid Tumors [RECIST] 1.1.) after first or second line platinum-based chemotherapy, for which treatment with PLD was indicated. Platinum-based therapy was defined as treatment with carboplatin, cisplatin or another organoplatinum compound. Platinum-resistant was defined as having a platinum-free interval of < 12 months after first- or second-line platinum-based chemotherapy, or having disease progression while receiving second-line platinum-based chemotherapy.",
            "criterions": [
                {
                    "exact_snippets": [
                        "recurrent or persistent platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma"
                    ],
                    "criterion": "carcinoma type",
                    "requirement_type": "specific type",
                    "expected_value": [
                        "epithelial ovarian",
                        "fallopian tube",
                        "primary peritoneal"
                    ]
                },
                {
                    "exact_snippets": [
                        "measurable disease",
                        "as defined by the Response Evaluation Criteria in Solid Tumors [RECIST] 1.1."
                    ],
                    "criterion": "disease",
                    "requirement_type": "measurability",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "after first or second line platinum-based chemotherapy"
                    ],
                    "criterion": "chemotherapy line",
                    "requirement_type": "completion",
                    "expected_value": [
                        "first",
                        "second"
                    ]
                },
                {
                    "exact_snippets": [
                        "treatment with PLD was indicated"
                    ],
                    "criterion": "PLD treatment",
                    "requirement_type": "indication",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Platinum-based therapy was defined as treatment with carboplatin, cisplatin or another organoplatinum compound"
                    ],
                    "criterion": "platinum-based therapy",
                    "requirement_type": "specific drugs",
                    "expected_value": [
                        "carboplatin",
                        "cisplatin",
                        "organoplatinum compound"
                    ]
                },
                {
                    "exact_snippets": [
                        "Platinum-resistant was defined as having a platinum-free interval of < 12 months"
                    ],
                    "criterion": "platinum-free interval",
                    "requirement_type": "duration",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<",
                                "value": 12
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "having disease progression while receiving second-line platinum-based chemotherapy"
                    ],
                    "criterion": "disease progression",
                    "requirement_type": "timing",
                    "expected_value": "during second-line platinum-based chemotherapy"
                }
            ]
        },
        {
            "line": "Subjects were allowed to have received, but were not required to have received:",
            "criterions": [
                {
                    "exact_snippets": [
                        "Subjects were allowed to have received"
                    ],
                    "criterion": "prior treatment",
                    "requirement_type": "allowance",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "but were not required to have received"
                    ],
                    "criterion": "prior treatment",
                    "requirement_type": "requirement",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "* one additional cytotoxic regimen and/or poly adenosine diphosphate-ribose polymerase inhibitor for management of recurrent or persistent disease.",
            "criterions": [
                {
                    "exact_snippets": [
                        "one additional cytotoxic regimen"
                    ],
                    "criterion": "cytotoxic regimen",
                    "requirement_type": "quantity",
                    "expected_value": ">= 1"
                },
                {
                    "exact_snippets": [
                        "poly adenosine diphosphate-ribose polymerase inhibitor"
                    ],
                    "criterion": "poly adenosine diphosphate-ribose polymerase inhibitor",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "management of recurrent or persistent disease"
                    ],
                    "criterion": "disease",
                    "requirement_type": "status",
                    "expected_value": [
                        "recurrent",
                        "persistent"
                    ]
                }
            ]
        },
        {
            "line": "* biologic therapy (e.g., bevacizumab) as part of their primary treatment regimen or part of their treatment for management of recurrent or persistent disease.",
            "criterions": [
                {
                    "exact_snippets": [
                        "biologic therapy (e.g., bevacizumab)"
                    ],
                    "criterion": "biologic therapy",
                    "requirement_type": "inclusion",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "2. Histologic documentation of the original primary tumor.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Histologic documentation of the original primary tumor"
                    ],
                    "criterion": "original primary tumor",
                    "requirement_type": "histologic documentation",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "3. Documented radiographic disease progression < 12 months after the last dose of first- or second-line platinum-based chemotherapy.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Documented radiographic disease progression"
                    ],
                    "criterion": "radiographic disease progression",
                    "requirement_type": "documentation",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "radiographic disease progression < 12 months after the last dose of first- or second-line platinum-based chemotherapy"
                    ],
                    "criterion": "radiographic disease progression",
                    "requirement_type": "time since last dose of platinum-based chemotherapy",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<",
                                "value": 12
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "4. Subjects in Phase 2 must have had disease amenable to biopsy and must have been willing to undergo pre- and post-treatment tumor biopsies. Optional for Phase 1.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Phase 2 must have had disease amenable to biopsy"
                    ],
                    "criterion": "disease",
                    "requirement_type": "amenability to biopsy",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "must have been willing to undergo pre- and post-treatment tumor biopsies"
                    ],
                    "criterion": "willingness",
                    "requirement_type": "undergo pre- and post-treatment tumor biopsies",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "Note: archival tissue was requested for all subjects preferably from primary tumor site prior to cancer treatment; however, archival tissue was not a requirement for study entry.",
            "criterions": [
                {
                    "exact_snippets": [
                        "archival tissue was requested",
                        "preferably from primary tumor site"
                    ],
                    "criterion": "archival tissue",
                    "requirement_type": "source",
                    "expected_value": "primary tumor site"
                },
                {
                    "exact_snippets": [
                        "archival tissue was requested",
                        "prior to cancer treatment"
                    ],
                    "criterion": "archival tissue",
                    "requirement_type": "timing",
                    "expected_value": "prior to cancer treatment"
                }
            ]
        },
        {
            "line": "5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Eastern Cooperative Oncology Group (ECOG) performance status"
                    ],
                    "criterion": "ECOG performance status",
                    "requirement_type": "value",
                    "expected_value": [
                        "0",
                        "1"
                    ]
                }
            ]
        },
        {
            "line": "6. Laboratory parameters for vital functions should have been in the normal range. Laboratory abnormalities that were not clinically significant were generally permitted, except for the following laboratory parameters, which must have been within the ranges specified, regardless of clinical significance:",
            "criterions": [
                {
                    "exact_snippets": [
                        "Laboratory parameters for vital functions"
                    ],
                    "criterion": "laboratory parameters for vital functions",
                    "requirement_type": "range",
                    "expected_value": "normal"
                },
                {
                    "exact_snippets": [
                        "Laboratory abnormalities that were not clinically significant were generally permitted"
                    ],
                    "criterion": "laboratory abnormalities",
                    "requirement_type": "clinical significance",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "laboratory parameters, which must have been within the ranges specified"
                    ],
                    "criterion": "laboratory parameters",
                    "requirement_type": "range",
                    "expected_value": "specified"
                }
            ]
        },
        {
            "line": "* Hemoglobin: ≥ 9 g/dL",
            "criterions": [
                {
                    "exact_snippets": [
                        "Hemoglobin: ≥ 9 g/dL"
                    ],
                    "criterion": "hemoglobin",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 9
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Neutrophil count: ≥ 1.5 x 10^9/L",
            "criterions": [
                {
                    "exact_snippets": [
                        "Neutrophil count: ≥ 1.5 x 10^9/L"
                    ],
                    "criterion": "neutrophil",
                    "requirement_type": "count",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 1500000000.0
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Platelet count: ≥ 100,000/mm^3",
            "criterions": [
                {
                    "exact_snippets": [
                        "Platelet count: ≥ 100,000/mm^3"
                    ],
                    "criterion": "platelet",
                    "requirement_type": "count",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 100000
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Serum creatinine: ≤ 1.5 x institutional upper limit of normal (ULN), or creatinine clearance ≥ 50 mL/min (by Cockcroft-Gault formula)",
            "criterions": [
                {
                    "exact_snippets": [
                        "Serum creatinine: ≤ 1.5 x institutional upper limit of normal (ULN)"
                    ],
                    "criterion": "serum creatinine",
                    "requirement_type": "quantity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 1.5
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "creatinine clearance ≥ 50 mL/min (by Cockcroft-Gault formula)"
                    ],
                    "criterion": "creatinine clearance",
                    "requirement_type": "quantity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 50
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Serum bilirubin: ≤ 1.2 mg/dL",
            "criterions": [
                {
                    "exact_snippets": [
                        "Serum bilirubin: ≤ 1.2 mg/dL"
                    ],
                    "criterion": "serum bilirubin",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 1.2
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT): ≤ 2.5 x ULN",
            "criterions": [
                {
                    "exact_snippets": [
                        "Aspartate aminotransferase (AST)"
                    ],
                    "criterion": "aspartate aminotransferase",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 2.5
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "alanine aminotransferase (ALT)"
                    ],
                    "criterion": "alanine aminotransferase",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 2.5
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Alkaline phosphatase: ≤ 2.5 x ULN",
            "criterions": [
                {
                    "exact_snippets": [
                        "Alkaline phosphatase: ≤ 2.5 x ULN"
                    ],
                    "criterion": "alkaline phosphatase",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 2.5
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "7. Age ≥18 years.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Age ≥18 years"
                    ],
                    "criterion": "age",
                    "requirement_type": "minimum",
                    "expected_value": {
                        "operator": ">=",
                        "value": 18
                    }
                }
            ]
        },
        {
            "line": "8. Able and willing to give valid written informed consent.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Able and willing to give valid written informed consent"
                    ],
                    "criterion": "informed consent",
                    "requirement_type": "ability and willingness",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "9. Body weight > 30 kg.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Body weight > 30 kg"
                    ],
                    "criterion": "body weight",
                    "requirement_type": "comparison",
                    "expected_value": {
                        "operator": ">",
                        "value": 30
                    }
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": [
                        "Healthy volunteers allowed"
                    ],
                    "criterion": "volunteer health status",
                    "requirement_type": "allowance",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "Must be FEMALE",
            "criterions": [
                {
                    "exact_snippets": [
                        "Must be FEMALE"
                    ],
                    "criterion": "gender",
                    "requirement_type": "specific value",
                    "expected_value": "female"
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": [
                        "minimum age of 18 Years"
                    ],
                    "criterion": "age",
                    "requirement_type": "minimum",
                    "expected_value": {
                        "operator": ">=",
                        "value": 18
                    }
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "2. Subjects with platinum-refractory disease, defined as disease progression while receiving first line platinum-based therapy.",
            "criterions": [
                {
                    "exact_snippets": [
                        "platinum-refractory disease"
                    ],
                    "criterion": "platinum-refractory disease",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "disease progression while receiving first line platinum-based therapy"
                    ],
                    "criterion": "disease progression",
                    "requirement_type": "condition",
                    "expected_value": "while receiving first line platinum-based therapy"
                }
            ]
        },
        {
            "line": "3. Clinically significant persistent immune-related adverse events following prior therapy.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Clinically significant persistent immune-related adverse events"
                    ],
                    "criterion": "immune-related adverse events",
                    "requirement_type": "severity",
                    "expected_value": "clinically significant"
                },
                {
                    "exact_snippets": [
                        "Clinically significant persistent immune-related adverse events"
                    ],
                    "criterion": "immune-related adverse events",
                    "requirement_type": "persistence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "following prior therapy"
                    ],
                    "criterion": "prior therapy",
                    "requirement_type": "occurrence",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "5. Subjects with clinically significant cardiovascular disease. This included:",
            "criterions": [
                {
                    "exact_snippets": [
                        "clinically significant cardiovascular disease"
                    ],
                    "criterion": "cardiovascular disease",
                    "requirement_type": "severity",
                    "expected_value": "clinically significant"
                }
            ]
        },
        {
            "line": "1. Resistant hypertension.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Resistant hypertension"
                    ],
                    "criterion": "hypertension",
                    "requirement_type": "resistance",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "2. Myocardial infarction or unstable angina within 6 months prior to Day 1 of the study.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Myocardial infarction",
                        "within 6 months prior to Day 1 of the study"
                    ],
                    "criterion": "myocardial infarction",
                    "requirement_type": "time since occurrence",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 6
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "unstable angina",
                        "within 6 months prior to Day 1 of the study"
                    ],
                    "criterion": "unstable angina",
                    "requirement_type": "time since occurrence",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 6
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "3. History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications, except for atrial fibrillation that is well controlled with anti-arrhythmic medication.",
            "criterions": [
                {
                    "exact_snippets": [
                        "History of serious ventricular arrhythmia"
                    ],
                    "criterion": "ventricular arrhythmia",
                    "requirement_type": "history",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "ventricular tachycardia"
                    ],
                    "criterion": "ventricular tachycardia",
                    "requirement_type": "history",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "ventricular fibrillation"
                    ],
                    "criterion": "ventricular fibrillation",
                    "requirement_type": "history",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "cardiac arrhythmias requiring anti-arrhythmic medications"
                    ],
                    "criterion": "cardiac arrhythmias",
                    "requirement_type": "medication requirement",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "atrial fibrillation that is well controlled with anti-arrhythmic medication"
                    ],
                    "criterion": "atrial fibrillation",
                    "requirement_type": "control with medication",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "4. Baseline ejection fraction ≤ 50% as assessed by echocardiogram or multiple-gated acquisition.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Baseline ejection fraction",
                        "≤ 50%"
                    ],
                    "criterion": "ejection fraction",
                    "requirement_type": "baseline value",
                    "expected_value": {
                        "operator": "<=",
                        "value": 50
                    }
                },
                {
                    "exact_snippets": [
                        "as assessed by echocardiogram"
                    ],
                    "criterion": "echocardiogram",
                    "requirement_type": "assessment method",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "as assessed by",
                        "multiple-gated acquisition"
                    ],
                    "criterion": "multiple-gated acquisition",
                    "requirement_type": "assessment method",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "5. New York Heart Association Class II or higher congestive heart failure.",
            "criterions": [
                {
                    "exact_snippets": [
                        "New York Heart Association Class II or higher congestive heart failure"
                    ],
                    "criterion": "New York Heart Association class",
                    "requirement_type": "severity",
                    "expected_value": ">= II"
                }
            ]
        },
        {
            "line": "6. Grade 2 or higher peripheral ischemia, except for brief (< 24 hours) episodes of ischemia managed non-surgically and without permanent deficit.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Grade 2 or higher peripheral ischemia"
                    ],
                    "criterion": "peripheral ischemia",
                    "requirement_type": "severity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 2
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "brief (< 24 hours) episodes of ischemia"
                    ],
                    "criterion": "ischemia episodes",
                    "requirement_type": "duration",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<",
                                "value": 24
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "6. History of pneumonitis or interstitial lung disease.",
            "criterions": [
                {
                    "exact_snippets": [
                        "History of pneumonitis"
                    ],
                    "criterion": "pneumonitis",
                    "requirement_type": "history",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "History of",
                        "interstitial lung disease"
                    ],
                    "criterion": "interstitial lung disease",
                    "requirement_type": "history",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "7. Active, suspected or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, Wegner's granulomatosis, active Hashimoto's thyroiditis, rheumatoid arthritis, lupus, scleroderma and its variants, multiple sclerosis, myasthenia gravis). 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 were permitted.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Active, suspected or prior documented autoimmune disease"
                    ],
                    "criterion": "autoimmune disease",
                    "requirement_type": "status",
                    "expected_value": [
                        "active",
                        "suspected",
                        "prior documented"
                    ]
                },
                {
                    "exact_snippets": [
                        "inflammatory bowel disease"
                    ],
                    "criterion": "inflammatory bowel disease",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "celiac disease"
                    ],
                    "criterion": "celiac disease",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Wegner's granulomatosis"
                    ],
                    "criterion": "Wegner's granulomatosis",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "active Hashimoto's thyroiditis"
                    ],
                    "criterion": "Hashimoto's thyroiditis",
                    "requirement_type": "status",
                    "expected_value": "active"
                },
                {
                    "exact_snippets": [
                        "rheumatoid arthritis"
                    ],
                    "criterion": "rheumatoid arthritis",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "lupus"
                    ],
                    "criterion": "lupus",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "scleroderma and its variants"
                    ],
                    "criterion": "scleroderma",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "multiple sclerosis"
                    ],
                    "criterion": "multiple sclerosis",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "myasthenia gravis"
                    ],
                    "criterion": "myasthenia gravis",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Vitiligo"
                    ],
                    "criterion": "Vitiligo",
                    "requirement_type": "presence",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "type I diabetes mellitus"
                    ],
                    "criterion": "type I diabetes mellitus",
                    "requirement_type": "presence",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "residual hypothyroidism due to autoimmune condition only requiring hormone replacement"
                    ],
                    "criterion": "residual hypothyroidism",
                    "requirement_type": "treatment requirement",
                    "expected_value": "hormone replacement"
                },
                {
                    "exact_snippets": [
                        "psoriasis not requiring systemic treatment"
                    ],
                    "criterion": "psoriasis",
                    "requirement_type": "treatment requirement",
                    "expected_value": "not requiring systemic treatment"
                },
                {
                    "exact_snippets": [
                        "conditions not expected to recur in the absence of an external trigger"
                    ],
                    "criterion": "conditions",
                    "requirement_type": "recurrence expectation",
                    "expected_value": "not expected to recur in the absence of an external trigger"
                }
            ]
        },
        {
            "line": "8. Other malignancy within 2 years prior to Day 1 of the study, except for those treated with surgical intervention only.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Other malignancy within 2 years prior to Day 1 of the study"
                    ],
                    "criterion": "other malignancy",
                    "requirement_type": "time since diagnosis",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 2
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "except for those treated with surgical intervention only"
                    ],
                    "criterion": "treatment",
                    "requirement_type": "type",
                    "expected_value": "surgical intervention only"
                }
            ]
        },
        {
            "line": "9. Subjects with clinical symptoms or signs of gastrointestinal obstruction and/or who required drainage gastrostomy tube and/or parenteral hydration or nutrition.",
            "criterions": [
                {
                    "exact_snippets": [
                        "clinical symptoms or signs of gastrointestinal obstruction"
                    ],
                    "criterion": "gastrointestinal obstruction",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "required drainage gastrostomy tube"
                    ],
                    "criterion": "drainage gastrostomy tube",
                    "requirement_type": "requirement",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "required",
                        "parenteral hydration or nutrition"
                    ],
                    "criterion": "parenteral hydration or nutrition",
                    "requirement_type": "requirement",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "10. Known immunodeficiency or human immunodeficiency virus, Hepatitis B or Hepatitis C positivity.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Known immunodeficiency"
                    ],
                    "criterion": "immunodeficiency",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "human immunodeficiency virus"
                    ],
                    "criterion": "human immunodeficiency virus",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Hepatitis B",
                        "positivity"
                    ],
                    "criterion": "Hepatitis B",
                    "requirement_type": "positivity",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Hepatitis C",
                        "positivity"
                    ],
                    "criterion": "Hepatitis C",
                    "requirement_type": "positivity",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "11. History of severe allergic reactions to any unknown allergens or components of the study drugs.",
            "criterions": [
                {
                    "exact_snippets": [
                        "History of severe allergic reactions"
                    ],
                    "criterion": "allergic reactions",
                    "requirement_type": "severity",
                    "expected_value": "severe"
                },
                {
                    "exact_snippets": [
                        "History of severe allergic reactions to any unknown allergens"
                    ],
                    "criterion": "allergic reactions",
                    "requirement_type": "cause",
                    "expected_value": "unknown allergens"
                },
                {
                    "exact_snippets": [
                        "History of severe allergic reactions to any",
                        "components of the study drugs"
                    ],
                    "criterion": "allergic reactions",
                    "requirement_type": "cause",
                    "expected_value": "components of the study drugs"
                }
            ]
        },
        {
            "line": "12. Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).",
            "criterions": [
                {
                    "exact_snippets": [
                        "serious infections"
                    ],
                    "criterion": "infections",
                    "requirement_type": "severity",
                    "expected_value": "serious"
                },
                {
                    "exact_snippets": [
                        "serious infections requiring antibiotics"
                    ],
                    "criterion": "antibiotics",
                    "requirement_type": "requirement",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "bleeding disorders"
                    ],
                    "criterion": "bleeding disorders",
                    "requirement_type": "presence",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "13. Prior treatment in any other interventional clinical trial within 4 weeks prior to Day 1 of the study.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Prior treatment in any other interventional clinical trial"
                    ],
                    "criterion": "prior treatment in interventional clinical trial",
                    "requirement_type": "time since last treatment",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 4
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "14. Mental impairment that may have compromised compliance with the requirements of the study.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Mental impairment"
                    ],
                    "criterion": "mental impairment",
                    "requirement_type": "presence",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "15. Lack of availability for immunological and clinical follow-up assessment.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Lack of availability for immunological"
                    ],
                    "criterion": "immunological follow-up assessment",
                    "requirement_type": "availability",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "Lack of availability for",
                        "clinical follow-up assessment"
                    ],
                    "criterion": "clinical follow-up assessment",
                    "requirement_type": "availability",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "16. Women of childbearing potential who were found to be pregnant as evidenced by positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) or nursing. NOTE: Pregnancy tests were not required for subjects who were not of childbearing potential as defined in #17.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Women of childbearing potential",
                        "found to be pregnant",
                        "positive serum pregnancy test"
                    ],
                    "criterion": "pregnancy",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "positive serum pregnancy test",
                        "minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin"
                    ],
                    "criterion": "serum pregnancy test sensitivity",
                    "requirement_type": "minimum sensitivity",
                    "expected_value": {
                        "operator": ">=",
                        "value": 25
                    }
                },
                {
                    "exact_snippets": [
                        "nursing"
                    ],
                    "criterion": "nursing",
                    "requirement_type": "status",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "17. Female subjects of childbearing potential who were sexually active with a nonsterilized male partner must have used at least one highly effective method of contraception from screening, and must have agreed to continue using such precautions for 90 days after the final dose of investigational product (durvalumab). Male partners of a female subject must have used male condom plus spermicide throughout this period (from screening and for 90 days after subject's receipt of the final dose of investigational product). Cessation of birth control after this point should have been discussed with a responsible physician. Not engaging in sexual activity for the total duration of the trial and the drug washout period was an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method were not acceptable methods of birth control.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Female subjects of childbearing potential"
                    ],
                    "criterion": "female subjects",
                    "requirement_type": "childbearing potential",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "sexually active with a nonsterilized male partner"
                    ],
                    "criterion": "sexual activity",
                    "requirement_type": "partner sterilization status",
                    "expected_value": "nonsterilized"
                },
                {
                    "exact_snippets": [
                        "must have used at least one highly effective method of contraception from screening"
                    ],
                    "criterion": "contraception method",
                    "requirement_type": "effectiveness",
                    "expected_value": "highly effective"
                },
                {
                    "exact_snippets": [
                        "must have agreed to continue using such precautions for 90 days after the final dose of investigational product"
                    ],
                    "criterion": "contraception method",
                    "requirement_type": "duration of use",
                    "expected_value": "90 days after final dose"
                },
                {
                    "exact_snippets": [
                        "Male partners of a female subject must have used male condom plus spermicide throughout this period"
                    ],
                    "criterion": "male partner contraception",
                    "requirement_type": "method",
                    "expected_value": [
                        "male condom",
                        "spermicide"
                    ]
                },
                {
                    "exact_snippets": [
                        "Not engaging in sexual activity for the total duration of the trial and the drug washout period was an acceptable practice"
                    ],
                    "criterion": "sexual activity",
                    "requirement_type": "engagement",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "periodic abstinence, the rhythm method, and the withdrawal method were not acceptable methods of birth control"
                    ],
                    "criterion": "birth control method",
                    "requirement_type": "acceptability",
                    "expected_value": [
                        "periodic abstinence",
                        "rhythm method",
                        "withdrawal method"
                    ]
                }
            ]
        },
        {
            "line": "Female subjects should have refrained from breastfeeding throughout the period described above.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Female subjects"
                    ],
                    "criterion": "gender",
                    "requirement_type": "specificity",
                    "expected_value": "female"
                },
                {
                    "exact_snippets": [
                        "refrained from breastfeeding"
                    ],
                    "criterion": "breastfeeding",
                    "requirement_type": "activity",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "NOTE: For the standard of care, PLD (Doxil®, Caelyx®), the package insert advises females of reproductive potential to use effective contraception during and for 6 months after last treatment with the drug. Therefore, all subjects of childbearing potential on this study should have continued contraception use for 6 months after the last PLD administration.",
            "criterions": [
                {
                    "exact_snippets": [
                        "females of reproductive potential"
                    ],
                    "criterion": "reproductive potential",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "use effective contraception during and for 6 months after last treatment"
                    ],
                    "criterion": "contraception use",
                    "requirement_type": "duration",
                    "expected_value": "6 months after last treatment"
                },
                {
                    "exact_snippets": [
                        "all subjects of childbearing potential"
                    ],
                    "criterion": "childbearing potential",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "continued contraception use for 6 months after the last PLD administration"
                    ],
                    "criterion": "contraception use",
                    "requirement_type": "duration",
                    "expected_value": "6 months after last PLD administration"
                }
            ]
        },
        {
            "line": "Females of childbearing potential were defined as those who were not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or post-menopausal.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Females of childbearing potential"
                    ],
                    "criterion": "females of childbearing potential",
                    "requirement_type": "definition",
                    "expected_value": "not surgically sterile or post-menopausal"
                },
                {
                    "exact_snippets": [
                        "not surgically sterile"
                    ],
                    "criterion": "surgical sterility",
                    "requirement_type": "status",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "bilateral tubal ligation"
                    ],
                    "criterion": "bilateral tubal ligation",
                    "requirement_type": "status",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "bilateral oophorectomy"
                    ],
                    "criterion": "bilateral oophorectomy",
                    "requirement_type": "status",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "complete hysterectomy"
                    ],
                    "criterion": "complete hysterectomy",
                    "requirement_type": "status",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "post-menopausal"
                    ],
                    "criterion": "post-menopausal",
                    "requirement_type": "status",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "Females were considered post-menopausal if they had been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements applied:",
            "criterions": [
                {
                    "exact_snippets": [
                        "Females"
                    ],
                    "criterion": "gender",
                    "requirement_type": "specificity",
                    "expected_value": "female"
                },
                {
                    "exact_snippets": [
                        "post-menopausal"
                    ],
                    "criterion": "menopausal status",
                    "requirement_type": "specificity",
                    "expected_value": "post-menopausal"
                },
                {
                    "exact_snippets": [
                        "amenorrheic for 12 months"
                    ],
                    "criterion": "amenorrhea duration",
                    "requirement_type": "duration",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 12
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "without an alternative medical cause"
                    ],
                    "criterion": "alternative medical cause for amenorrhea",
                    "requirement_type": "absence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "age-specific requirements"
                    ],
                    "criterion": "age",
                    "requirement_type": "specificity",
                    "expected_value": "age-specific requirements"
                }
            ]
        },
        {
            "line": "* Females < 50 years of age were considered post-menopausal if they had been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they had luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).",
            "criterions": [
                {
                    "exact_snippets": [
                        "Females < 50 years of age"
                    ],
                    "criterion": "age",
                    "requirement_type": "range",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<",
                                "value": 50
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "amenorrheic for 12 months or more"
                    ],
                    "criterion": "amenorrhea",
                    "requirement_type": "duration",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 12
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "cessation of exogenous hormonal treatments"
                    ],
                    "criterion": "exogenous hormonal treatments",
                    "requirement_type": "cessation",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "luteinizing hormone",
                        "levels in the post-menopausal range for the institution"
                    ],
                    "criterion": "luteinizing hormone",
                    "requirement_type": "level",
                    "expected_value": "post-menopausal range"
                },
                {
                    "exact_snippets": [
                        "follicle-stimulating hormone",
                        "levels in the post-menopausal range for the institution"
                    ],
                    "criterion": "follicle-stimulating hormone",
                    "requirement_type": "level",
                    "expected_value": "post-menopausal range"
                },
                {
                    "exact_snippets": [
                        "surgical sterilization (bilateral oophorectomy or hysterectomy)"
                    ],
                    "criterion": "surgical sterilization",
                    "requirement_type": "procedure",
                    "expected_value": [
                        "bilateral oophorectomy",
                        "hysterectomy"
                    ]
                }
            ]
        },
        {
            "line": "* Females ≥ 50 years of age were considered post-menopausal if they had been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).",
            "criterions": [
                {
                    "exact_snippets": [
                        "Females"
                    ],
                    "criterion": "gender",
                    "requirement_type": "specificity",
                    "expected_value": "female"
                },
                {
                    "exact_snippets": [
                        "≥ 50 years of age"
                    ],
                    "criterion": "age",
                    "requirement_type": "range",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 50
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "amenorrheic for 12 months or more"
                    ],
                    "criterion": "amenorrhea",
                    "requirement_type": "duration",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 12
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "cessation of all exogenous hormonal treatments"
                    ],
                    "criterion": "exogenous hormonal treatments",
                    "requirement_type": "cessation",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "radiation-induced menopause",
                        "last menses > 1 year ago"
                    ],
                    "criterion": "radiation-induced menopause",
                    "requirement_type": "duration since last menses",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">",
                                "value": 1
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "chemotherapy-induced menopause",
                        "last menses > 1 year ago"
                    ],
                    "criterion": "chemotherapy-induced menopause",
                    "requirement_type": "duration since last menses",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">",
                                "value": 1
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)"
                    ],
                    "criterion": "surgical sterilization",
                    "requirement_type": "procedure",
                    "expected_value": [
                        "bilateral oophorectomy",
                        "bilateral salpingectomy",
                        "hysterectomy"
                    ]
                }
            ]
        },
        {
            "line": "A highly effective method of contraception was defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Note that some contraception methods were not considered highly effective (e.g., male or female condom with or without spermicide; female cap, diaphragm, or sponge with or without spermicide; non-copper containing intrauterine device; progestogen-only oral hormonal contraceptive pills where inhibition of ovulation is not the primary mode of action [excluding Cerazette/desogestrel which is considered highly effective]; and triphasic combined oral contraceptive pills).",
            "criterions": [
                {
                    "exact_snippets": [
                        "highly effective method of contraception",
                        "defined as one that results in a low failure rate",
                        "less than 1% per year"
                    ],
                    "criterion": "contraception method",
                    "requirement_type": "effectiveness",
                    "expected_value": "highly effective"
                },
                {
                    "exact_snippets": [
                        "male or female condom with or without spermicide"
                    ],
                    "criterion": "contraception method",
                    "requirement_type": "effectiveness",
                    "expected_value": "not highly effective"
                },
                {
                    "exact_snippets": [
                        "female cap, diaphragm, or sponge with or without spermicide"
                    ],
                    "criterion": "contraception method",
                    "requirement_type": "effectiveness",
                    "expected_value": "not highly effective"
                },
                {
                    "exact_snippets": [
                        "non-copper containing intrauterine device"
                    ],
                    "criterion": "contraception method",
                    "requirement_type": "effectiveness",
                    "expected_value": "not highly effective"
                },
                {
                    "exact_snippets": [
                        "progestogen-only oral hormonal contraceptive pills where inhibition of ovulation is not the primary mode of action",
                        "excluding Cerazette/desogestrel which is considered highly effective"
                    ],
                    "criterion": "contraception method",
                    "requirement_type": "effectiveness",
                    "expected_value": "not highly effective"
                },
                {
                    "exact_snippets": [
                        "triphasic combined oral contraceptive pills"
                    ],
                    "criterion": "contraception method",
                    "requirement_type": "effectiveness",
                    "expected_value": "not highly effective"
                }
            ]
        },
        {
            "line": "18. Any condition that, in the clinical judgment of the treating physician, was likely to prevent the subject from complying with any aspect of the protocol or that may have put the subject at unacceptable risk.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Any condition that, in the clinical judgment of the treating physician, was likely to prevent the subject from complying with any aspect of the protocol"
                    ],
                    "criterion": "condition",
                    "requirement_type": "impact on protocol compliance",
                    "expected_value": "likely to prevent compliance"
                },
                {
                    "exact_snippets": [
                        "Any condition that, in the clinical judgment of the treating physician,",
                        "may have put the subject at unacceptable risk"
                    ],
                    "criterion": "condition",
                    "requirement_type": "risk level",
                    "expected_value": "unacceptable risk"
                }
            ]
        },
        {
            "line": "19. Subjects must not have donated blood while on study and for at least 90 days following the last durvalumab treatment.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Subjects must not have donated blood"
                    ],
                    "criterion": "blood donation",
                    "requirement_type": "activity",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "at least 90 days following the last durvalumab treatment"
                    ],
                    "criterion": "post-treatment period",
                    "requirement_type": "duration",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 90
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "20. History of allogeneic organ transplant.",
            "criterions": [
                {
                    "exact_snippets": [
                        "History of allogeneic organ transplant"
                    ],
                    "criterion": "allogeneic organ transplant",
                    "requirement_type": "history",
                    "expected_value": true
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [
        {
            "line": "1. Prior exposure to doxorubicin, PLD or any other anthracycline, motolimod and other toll-like receptor agonists, durvalumab or checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1)/anti-programmed cell death ligand-1 (PD-L1) antibodies.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Prior exposure to doxorubicin"
                    ],
                    "criterion": "doxorubicin",
                    "requirement_type": "prior exposure",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Prior exposure to PLD"
                    ],
                    "criterion": "PLD",
                    "requirement_type": "prior exposure",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Prior exposure to any other anthracycline"
                    ],
                    "criterion": "anthracycline",
                    "requirement_type": "prior exposure",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Prior exposure to motolimod"
                    ],
                    "criterion": "motolimod",
                    "requirement_type": "prior exposure",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Prior exposure to other toll-like receptor agonists"
                    ],
                    "criterion": "toll-like receptor agonists",
                    "requirement_type": "prior exposure",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Prior exposure to durvalumab"
                    ],
                    "criterion": "durvalumab",
                    "requirement_type": "prior exposure",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Prior exposure to checkpoint inhibitors"
                    ],
                    "criterion": "checkpoint inhibitors",
                    "requirement_type": "prior exposure",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Prior exposure to anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibodies"
                    ],
                    "criterion": "anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibodies",
                    "requirement_type": "prior exposure",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Prior exposure to anti-programmed cell death-1 (PD-1)/anti-programmed cell death ligand-1 (PD-L1) antibodies"
                    ],
                    "criterion": "anti-programmed cell death-1 (PD-1)/anti-programmed cell death ligand-1 (PD-L1) antibodies",
                    "requirement_type": "prior exposure",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "4. Subjects with history or evidence upon physical examination of central nervous system disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or, within 6 months prior to Day 1 of this study, history of cerebrovascular accident (stroke), transient ischemic attack or subarachnoid hemorrhage.",
            "criterions": [
                {
                    "exact_snippets": [
                        "history or evidence upon physical examination of central nervous system disease"
                    ],
                    "criterion": "central nervous system disease",
                    "requirement_type": "history or evidence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "primary brain tumor"
                    ],
                    "criterion": "primary brain tumor",
                    "requirement_type": "presence",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "seizures not controlled with standard medical therapy"
                    ],
                    "criterion": "seizures",
                    "requirement_type": "control",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "any brain metastases"
                    ],
                    "criterion": "brain metastases",
                    "requirement_type": "presence",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "within 6 months prior to Day 1 of this study, history of cerebrovascular accident (stroke)"
                    ],
                    "criterion": "cerebrovascular accident (stroke)",
                    "requirement_type": "history",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 6
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "within 6 months prior to Day 1 of this study, history of transient ischemic attack"
                    ],
                    "criterion": "transient ischemic attack",
                    "requirement_type": "history",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 6
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "within 6 months prior to Day 1 of this study, history of subarachnoid hemorrhage"
                    ],
                    "criterion": "subarachnoid hemorrhage",
                    "requirement_type": "history",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 6
                            }
                        ]
                    }
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}