{
    "info": {
        "nct_id": "NCT03271372",
        "official_title": "A Multicenter, Randomized, Double-Blinded, Placebo-Controlled, Phase 3 Trial of Adjuvant Avelumab (Anti-PDL-1 Antibody) in Merkel Cell Carcinoma Patients With Lymph Node Metastases",
        "inclusion_criteria": "* Histologically confirmed MCC metastases in regional lymph node(s)\n\n  * Confirmation of the MCC diagnosis in the regional lymph node(s) is mandatory for trial participation\n  * (NOTE: In-transit metastases without regional nodal involvement could be allowed, but only after written approval of the medical monitor)\n* Must have completed definitive treatment for primary MCC and regional lymphatic metastases that included surgical removal (with/without adjuvant radiation therapy) or primary radiation therapy as determined by the treating investigator\n* Aged >= 18 years. Both men and women, and members of all races and ethnic groups are eligible for this trial.\n* Estimated life expectancy greater than 3 years\n* Must start the study treatment no more than 120 days from the start date of definitive therapy (the date of surgical removal of nodal metastases or the date of initiation of definitive radiation therapy, as applicable)\n* Eastern Co-Operative Group (Eastern Cooperative Oncology Group [ECOG]) performance score of 0 or 1\n* Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L\n* Platelet count ≥ 100 x 10^9/L\n* Hemoglobin ≥ 9 g/dL (may have been transfused)\n* Total bilirubin level ≤ 1.5 x the upper limit of normal (ULN) range\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 x ULN\n* Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula or by 24-hour urine collection for creatinine clearance or according to local institutional standard\n* Women of childbearing potential must have a negative serum or urine pregnancy test at screening\n* Both male and female subjects must be willing to use highly effective contraception (that is, methods with a failure rate of less than 1% per year) throughout the study and for at least 30 days after last avelumab treatment administration if the risk of conception exists\n\n  * (NOTE: The effects of the study treatment on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use highly effective contraception, as stipulated in national or local guidelines. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the treating physician should be informed immediately.)\n* Must have an ability to understand and the willingness to sign a written informed consent document\n* Must consent to allow the acquisition of existing formalin-fixed paraffin-embedded (FFPE) tumor tissue, either a block or unstained slides, for performance of correlative studies\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Clinical or radiologic suspicion of residual MCC at the time of enrollment\n* Suspicion or known history of distant metastatic MCC, which is not classifiable as local recurrence or regional metastasis\n* Any prior systemic therapy (e.g. adjuvant, neo-adjuvant or concurrent use of chemotherapy, immunotherapy or an investigational agent) for MCC at any time\n* Any prior intra-lesional MCC therapy within 180 days from day 1 of study treatment\n* Residual toxicity from prior therapy grade > 1 (National Cancer Institute [NCI]-Common Terminology Criteria for Adverse Events [NCI-CTCAE v 5.0]) that could interfere with study endpoints or put patient safety at risk\n* Previous malignant disease (other than Merkel cell carcinoma) diagnosed within 3 years from day 1 of study treatment that could interfere with study endpoints or put patient safety at risk\n\n  * (NOTE: Exception will be made for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ [skin, bladder, cervical, colorectal, breast] or low grade prostatic intraepithelial neoplasia or Grade 1 prostate cancer; any other neoplasm, which is adjudged by the treating investigator to have a low risk of recurrence during the study, could be enrolled only after written approval from the medical monitor)\n* Use of any systemic immunosuppressive treatments including corticosteroids, cyclosporine, mycophenolate mofetil et cetera, ongoing or within the last 3 months prior to day 1 of treatment\n\n  * (NOTE: Patients on physiologic dose of corticosteroids [≤ 10 mg/day of prednisone or equivalent] for long-term hormone-replacement therapy or those requiring short, intermittent courses of corticosteroids for hypersensitivity prophylaxis [such as for iodinated computed tomography (CT) contrast prophylaxis] or those using intranasal, inhaled, topical steroids, or local steroid injection [e.g., intra-articular injection] can be allowed)\n* Immunosuppressed status due to known human immunodeficiency virus (HIV) infection, severe uncontrolled diabetes, concurrent hematological malignancy, or other comorbidities\n* Uncontrolled intercurrent illness including, but not limited to, active serious infection, active hepatitis B or hepatitis C infection, uncontrolled seizure disorder, substance abuse disorder, or psychiatric illness/social situations that would limit compliance with study requirements or would put the patient at increased risk of complications during the study period\n* Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication\n* Active or history of any serious autoimmune disease, prior organ transplantation, including allogeneic stem-cell transplantation or immune-deficiencies that required treatment with systemic immunosuppressive drugs and could flare-up during study treatment\n\n  * (NOTE: Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible)\n* Other severe acute or chronic medical conditions including immune-mediated colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study\n* Known prior severe hypersensitivity to investigational product or any component in its formulations that could interfere with study endpoints or put patient safety at risk\n* Pregnant or breast-feeding women",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Histologically confirmed MCC metastases in regional lymph node(s)",
            "criterions": [
                {
                    "exact_snippets": "Histologically confirmed MCC metastases",
                    "criterion": "MCC metastases",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "histologically confirmed"
                        }
                    ]
                },
                {
                    "exact_snippets": "regional lymph node(s)",
                    "criterion": "regional lymph node involvement",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Confirmation of the MCC diagnosis in the regional lymph node(s) is mandatory for trial participation",
            "criterions": [
                {
                    "exact_snippets": "Confirmation of the MCC diagnosis in the regional lymph node(s) is mandatory",
                    "criterion": "MCC diagnosis in the regional lymph node(s)",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* (NOTE: In-transit metastases without regional nodal involvement could be allowed, but only after written approval of the medical monitor)",
            "criterions": [
                {
                    "exact_snippets": "In-transit metastases without regional nodal involvement could be allowed",
                    "criterion": "in-transit metastases",
                    "requirements": [
                        {
                            "requirement_type": "regional nodal involvement",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "only after written approval of the medical monitor",
                    "criterion": "written approval of the medical monitor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Must have completed definitive treatment for primary MCC and regional lymphatic metastases that included surgical removal (with/without adjuvant radiation therapy) or primary radiation therapy as determined by the treating investigator",
            "criterions": [
                {
                    "exact_snippets": "Must have completed definitive treatment for primary MCC and regional lymphatic metastases",
                    "criterion": "treatment completion",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "included surgical removal (with/without adjuvant radiation therapy) or primary radiation therapy",
                    "criterion": "treatment type",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "surgical removal",
                                "primary radiation therapy"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Aged >= 18 years. Both men and women, and members of all races and ethnic groups are eligible for this trial.",
            "criterions": [
                {
                    "exact_snippets": "Aged >= 18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Both men and women",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": [
                                "men",
                                "women"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "members of all races and ethnic groups",
                    "criterion": "race and ethnicity",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": "all races and ethnic groups"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Estimated life expectancy greater than 3 years",
            "criterions": [
                {
                    "exact_snippets": "Estimated life expectancy greater than 3 years",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 3,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Must start the study treatment no more than 120 days from the start date of definitive therapy (the date of surgical removal of nodal metastases or the date of initiation of definitive radiation therapy, as applicable)",
            "criterions": [
                {
                    "exact_snippets": "Must start the study treatment no more than 120 days from the start date of definitive therapy",
                    "criterion": "study treatment start date",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 120,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Co-Operative Group (Eastern Cooperative Oncology Group [ECOG]) performance score of 0 or 1",
            "criterions": [
                {
                    "exact_snippets": "Eastern Co-Operative Group (Eastern Cooperative Oncology Group [ECOG]) performance score of 0 or 1",
                    "criterion": "ECOG performance score",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L",
                    "criterion": "absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelet count ≥ 100 x 10^9/L",
            "criterions": [
                {
                    "exact_snippets": "Platelet count ≥ 100 x 10^9/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin ≥ 9 g/dL (may have been transfused)",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin ≥ 9 g/dL",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9,
                                "unit": "g/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "may have been transfused",
                    "criterion": "transfusion status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "may have been transfused"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin level ≤ 1.5 x the upper limit of normal (ULN) range",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin level ≤ 1.5 x the upper limit of normal (ULN) range",
                    "criterion": "total bilirubin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 x ULN",
            "criterions": [
                {
                    "exact_snippets": "Aspartate aminotransferase (AST) ... levels ≤ 2.5 x ULN",
                    "criterion": "aspartate aminotransferase (AST) levels",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alanine aminotransferase (ALT) levels ≤ 2.5 x ULN",
                    "criterion": "alanine aminotransferase (ALT) levels",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula or by 24-hour urine collection for creatinine clearance or according to local institutional standard",
            "criterions": [
                {
                    "exact_snippets": "Estimated creatinine clearance ≥ 30 mL/min",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 30,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of childbearing potential must have a negative serum or urine pregnancy test at screening",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential",
                    "criterion": "women of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "negative serum or urine pregnancy test",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Both male and female subjects must be willing to use highly effective contraception (that is, methods with a failure rate of less than 1% per year) throughout the study and for at least 30 days after last avelumab treatment administration if the risk of conception exists",
            "criterions": [
                {
                    "exact_snippets": "Both male and female subjects",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "male",
                                "female"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "willing to use highly effective contraception",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "methods with a failure rate of less than 1% per year",
                    "criterion": "contraception effectiveness",
                    "requirements": [
                        {
                            "requirement_type": "failure rate",
                            "expected_value": {
                                "operator": "<",
                                "value": 1,
                                "unit": "% per year"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "throughout the study and for at least 30 days after last avelumab treatment administration",
                    "criterion": "contraception duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "throughout the study and for at least 30 days after last avelumab treatment administration"
                        }
                    ]
                },
                {
                    "exact_snippets": "if the risk of conception exists",
                    "criterion": "risk of conception",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "exists"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* (NOTE: The effects of the study treatment on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use highly effective contraception, as stipulated in national or local guidelines. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the treating physician should be informed immediately.)",
            "criterions": [
                {
                    "exact_snippets": "women of childbearing potential",
                    "criterion": "women of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "men must agree to use highly effective contraception",
                    "criterion": "contraception use by men",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "women of childbearing potential ... must agree to use highly effective contraception",
                    "criterion": "contraception use by women of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Must have an ability to understand and the willingness to sign a written informed consent document",
            "criterions": [
                {
                    "exact_snippets": "Must have an ability to understand",
                    "criterion": "ability to understand",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "willingness to sign a written informed consent document",
                    "criterion": "willingness to sign informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Must consent to allow the acquisition of existing formalin-fixed paraffin-embedded (FFPE) tumor tissue, either a block or unstained slides, for performance of correlative studies",
            "criterions": [
                {
                    "exact_snippets": "Must consent to allow the acquisition of existing formalin-fixed paraffin-embedded (FFPE) tumor tissue",
                    "criterion": "consent for acquisition of FFPE tumor tissue",
                    "requirements": [
                        {
                            "requirement_type": "consent",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "existing formalin-fixed paraffin-embedded (FFPE) tumor tissue, either a block or unstained slides",
                    "criterion": "availability of FFPE tumor tissue",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "healthy volunteers",
                    "requirements": [
                        {
                            "requirement_type": "participation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "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": "* Clinical or radiologic suspicion of residual MCC at the time of enrollment",
            "criterions": [
                {
                    "exact_snippets": "Clinical or radiologic suspicion of residual MCC",
                    "criterion": "residual MCC",
                    "requirements": [
                        {
                            "requirement_type": "suspicion",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Suspicion or known history of distant metastatic MCC, which is not classifiable as local recurrence or regional metastasis",
            "criterions": [
                {
                    "exact_snippets": "Suspicion or known history of distant metastatic MCC",
                    "criterion": "distant metastatic MCC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "not classifiable as local recurrence",
                    "criterion": "local recurrence",
                    "requirements": [
                        {
                            "requirement_type": "classifiability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "not classifiable as ... regional metastasis",
                    "criterion": "regional metastasis",
                    "requirements": [
                        {
                            "requirement_type": "classifiability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any prior systemic therapy (e.g. adjuvant, neo-adjuvant or concurrent use of chemotherapy, immunotherapy or an investigational agent) for MCC at any time",
            "criterions": [
                {
                    "exact_snippets": "Any prior systemic therapy (e.g. adjuvant, neo-adjuvant or concurrent use of chemotherapy, immunotherapy or an investigational agent) for MCC",
                    "criterion": "prior systemic therapy for MCC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any prior intra-lesional MCC therapy within 180 days from day 1 of study treatment",
            "criterions": [
                {
                    "exact_snippets": "prior intra-lesional MCC therapy",
                    "criterion": "prior intra-lesional MCC therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 180,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Residual toxicity from prior therapy grade > 1 (National Cancer Institute [NCI]-Common Terminology Criteria for Adverse Events [NCI-CTCAE v 5.0]) that could interfere with study endpoints or put patient safety at risk",
            "criterions": [
                {
                    "exact_snippets": "Residual toxicity from prior therapy grade > 1 (National Cancer Institute [NCI]-Common Terminology Criteria for Adverse Events [NCI-CTCAE v 5.0])",
                    "criterion": "residual toxicity from prior therapy",
                    "requirements": [
                        {
                            "requirement_type": "grade",
                            "expected_value": {
                                "operator": ">",
                                "value": 1,
                                "unit": "NCI-CTCAE v 5.0"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Previous malignant disease (other than Merkel cell carcinoma) diagnosed within 3 years from day 1 of study treatment that could interfere with study endpoints or put patient safety at risk",
            "criterions": [
                {
                    "exact_snippets": "Previous malignant disease (other than Merkel cell carcinoma) diagnosed within 3 years from day 1 of study treatment",
                    "criterion": "previous malignant disease",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Previous malignant disease ... that could interfere with study endpoints",
                    "criterion": "interference with study endpoints",
                    "requirements": [
                        {
                            "requirement_type": "potential to interfere",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Previous malignant disease ... put patient safety at risk",
                    "criterion": "patient safety risk",
                    "requirements": [
                        {
                            "requirement_type": "potential to risk safety",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* (NOTE: Exception will be made for adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ [skin, bladder, cervical, colorectal, breast] or low grade prostatic intraepithelial neoplasia or Grade 1 prostate cancer; any other neoplasm, which is adjudged by the treating investigator to have a low risk of recurrence during the study, could be enrolled only after written approval from the medical monitor)",
            "criterions": [
                {
                    "exact_snippets": "adequately treated basal or squamous cell carcinoma of the skin",
                    "criterion": "basal or squamous cell carcinoma of the skin",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "adequately treated"
                        }
                    ]
                },
                {
                    "exact_snippets": "carcinoma in situ [skin, bladder, cervical, colorectal, breast]",
                    "criterion": "carcinoma in situ",
                    "requirements": [
                        {
                            "requirement_type": "location",
                            "expected_value": [
                                "skin",
                                "bladder",
                                "cervical",
                                "colorectal",
                                "breast"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "low grade prostatic intraepithelial neoplasia",
                    "criterion": "prostatic intraepithelial neoplasia",
                    "requirements": [
                        {
                            "requirement_type": "grade",
                            "expected_value": "low"
                        }
                    ]
                },
                {
                    "exact_snippets": "Grade 1 prostate cancer",
                    "criterion": "prostate cancer",
                    "requirements": [
                        {
                            "requirement_type": "grade",
                            "expected_value": "1"
                        }
                    ]
                },
                {
                    "exact_snippets": "any other neoplasm, which is adjudged by the treating investigator to have a low risk of recurrence during the study",
                    "criterion": "other neoplasm",
                    "requirements": [
                        {
                            "requirement_type": "risk of recurrence",
                            "expected_value": "low"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Use of any systemic immunosuppressive treatments including corticosteroids, cyclosporine, mycophenolate mofetil et cetera, ongoing or within the last 3 months prior to day 1 of treatment",
            "criterions": [
                {
                    "exact_snippets": "Use of any systemic immunosuppressive treatments including corticosteroids, cyclosporine, mycophenolate mofetil",
                    "criterion": "systemic immunosuppressive treatments",
                    "requirements": [
                        {
                            "requirement_type": "use",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "ongoing or within the last 3 months prior to day 1 of treatment",
                    "criterion": "time since last use of systemic immunosuppressive treatments",
                    "requirements": [
                        {
                            "requirement_type": "time since last use",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 3,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* (NOTE: Patients on physiologic dose of corticosteroids [≤ 10 mg/day of prednisone or equivalent] for long-term hormone-replacement therapy or those requiring short, intermittent courses of corticosteroids for hypersensitivity prophylaxis [such as for iodinated computed tomography (CT) contrast prophylaxis] or those using intranasal, inhaled, topical steroids, or local steroid injection [e.g., intra-articular injection] can be allowed)",
            "criterions": [
                {
                    "exact_snippets": "physiologic dose of corticosteroids [≤ 10 mg/day of prednisone or equivalent]",
                    "criterion": "corticosteroid dose",
                    "requirements": [
                        {
                            "requirement_type": "dose",
                            "expected_value": {
                                "operator": "<=",
                                "value": 10,
                                "unit": "mg/day of prednisone or equivalent"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "long-term hormone-replacement therapy",
                    "criterion": "hormone-replacement therapy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "long-term"
                        }
                    ]
                },
                {
                    "exact_snippets": "short, intermittent courses of corticosteroids for hypersensitivity prophylaxis",
                    "criterion": "corticosteroid courses for hypersensitivity prophylaxis",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "short, intermittent"
                        }
                    ]
                },
                {
                    "exact_snippets": "intranasal, inhaled, topical steroids, or local steroid injection",
                    "criterion": "steroid administration route",
                    "requirements": [
                        {
                            "requirement_type": "route",
                            "expected_value": [
                                "intranasal",
                                "inhaled",
                                "topical",
                                "local injection"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Immunosuppressed status due to known human immunodeficiency virus (HIV) infection, severe uncontrolled diabetes, concurrent hematological malignancy, or other comorbidities",
            "criterions": [
                {
                    "exact_snippets": "Immunosuppressed status due to known human immunodeficiency virus (HIV) infection",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Immunosuppressed status due to ... severe uncontrolled diabetes",
                    "criterion": "severe uncontrolled diabetes",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Immunosuppressed status due to ... concurrent hematological malignancy",
                    "criterion": "concurrent hematological malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Immunosuppressed status due to ... other comorbidities",
                    "criterion": "other comorbidities",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled intercurrent illness including, but not limited to, active serious infection, active hepatitis B or hepatitis C infection, uncontrolled seizure disorder, substance abuse disorder, or psychiatric illness/social situations that would limit compliance with study requirements or would put the patient at increased risk of complications during the study period",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled intercurrent illness including, but not limited to, active serious infection",
                    "criterion": "active serious infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active hepatitis B or hepatitis C infection",
                    "criterion": "active hepatitis B infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active hepatitis B or hepatitis C infection",
                    "criterion": "active hepatitis C infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled seizure disorder",
                    "criterion": "uncontrolled seizure disorder",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "substance abuse disorder",
                    "criterion": "substance abuse disorder",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "psychiatric illness/social situations that would limit compliance with study requirements",
                    "criterion": "psychiatric illness/social situations",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance",
                            "expected_value": "limit compliance with study requirements"
                        }
                    ]
                },
                {
                    "exact_snippets": "psychiatric illness/social situations ... would put the patient at increased risk of complications during the study period",
                    "criterion": "psychiatric illness/social situations",
                    "requirements": [
                        {
                            "requirement_type": "risk of complications",
                            "expected_value": "increased risk during the study period"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication",
            "criterions": [
                {
                    "exact_snippets": "Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment)",
                    "criterion": "cerebral vascular accident/stroke",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Clinically significant (i.e., active) cardiovascular disease: ... myocardial infarction (< 6 months prior to enrollment)",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Clinically significant (i.e., active) cardiovascular disease: ... unstable angina",
                    "criterion": "unstable angina",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Clinically significant (i.e., active) cardiovascular disease: ... congestive heart failure (≥ New York Heart Association Classification Class II)",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "New York Heart Association Classification Class"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Clinically significant (i.e., active) cardiovascular disease: ... serious cardiac arrhythmia requiring medication",
                    "criterion": "serious cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": "medication"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active or history of any serious autoimmune disease, prior organ transplantation, including allogeneic stem-cell transplantation or immune-deficiencies that required treatment with systemic immunosuppressive drugs and could flare-up during study treatment",
            "criterions": [
                {
                    "exact_snippets": "Active or history of any serious autoimmune disease",
                    "criterion": "autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "prior organ transplantation",
                    "criterion": "organ transplantation",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "including allogeneic stem-cell transplantation",
                    "criterion": "allogeneic stem-cell transplantation",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "immune-deficiencies that required treatment with systemic immunosuppressive drugs",
                    "criterion": "immune-deficiencies",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "systemic immunosuppressive drugs"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* (NOTE: Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible)",
            "criterions": [
                {
                    "exact_snippets": "diabetes type I",
                    "criterion": "diabetes type I",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "vitiligo",
                    "criterion": "vitiligo",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "psoriasis",
                    "criterion": "psoriasis",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hypo- or hyperthyroid diseases not requiring immunosuppressive treatment",
                    "criterion": "hypo- or hyperthyroid diseases",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": "not requiring immunosuppressive treatment"
                        },
                        {
                            "requirement_type": "eligibility",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Other severe acute or chronic medical conditions including immune-mediated colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study",
            "criterions": [
                {
                    "exact_snippets": "severe acute or chronic medical conditions including immune-mediated colitis",
                    "criterion": "immune-mediated colitis",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe acute or chronic"
                        }
                    ]
                },
                {
                    "exact_snippets": "severe acute or chronic medical conditions including ... inflammatory bowel disease",
                    "criterion": "inflammatory bowel disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe acute or chronic"
                        }
                    ]
                },
                {
                    "exact_snippets": "severe acute or chronic medical conditions including ... pneumonitis",
                    "criterion": "pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe acute or chronic"
                        }
                    ]
                },
                {
                    "exact_snippets": "severe acute or chronic medical conditions including ... pulmonary fibrosis",
                    "criterion": "pulmonary fibrosis",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe acute or chronic"
                        }
                    ]
                },
                {
                    "exact_snippets": "psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior",
                    "criterion": "suicidal ideation or behavior",
                    "requirements": [
                        {
                            "requirement_type": "recency",
                            "expected_value": "within the past year"
                        },
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "laboratory abnormalities that may increase the risk associated with study participation or study treatment administration",
                    "criterion": "laboratory abnormalities",
                    "requirements": [
                        {
                            "requirement_type": "risk",
                            "expected_value": "may increase"
                        }
                    ]
                },
                {
                    "exact_snippets": "laboratory abnormalities that ... may interfere with the interpretation of study results",
                    "criterion": "laboratory abnormalities",
                    "requirements": [
                        {
                            "requirement_type": "interference",
                            "expected_value": "may interfere with the interpretation of study results"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known prior severe hypersensitivity to investigational product or any component in its formulations that could interfere with study endpoints or put patient safety at risk",
            "criterions": [
                {
                    "exact_snippets": "Known prior severe hypersensitivity to investigational product",
                    "criterion": "hypersensitivity to investigational product",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        },
                        {
                            "requirement_type": "temporal",
                            "expected_value": "prior"
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity to ... any component in its formulations",
                    "criterion": "hypersensitivity to components in formulations",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant or breast-feeding women",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breast-feeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}