{
    "info": {
        "nct_id": "NCT03832673",
        "official_title": "PECULIAR: An Open Label, Monocenter, Single-arm, Phase 2 Study of Neoadjuvant Pembrolizumab and Epacadostat, Preceding Radical Cystectomy, for Patients With Muscle-invasive Bladder Cancer.",
        "inclusion_criteria": "1. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial\n2. Male/female participants who are at least 18 years of age will be enrolled in this study.\n3. A male participant must agree to use a contraception during the treatment period and for at least [120 days, corresponding to time needed to eliminate any study treatments) plus an additional 120 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose] after the last dose of study treatment and refrain from donating sperm during this period.\n4. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) or b.) A WOCBP who agrees to follow the contraceptive during the treatment period and for at least [120 days (corresponding to time needed to eliminate any study treatments) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity] after the last dose of study treatment.\n5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.\n6. Have adequate organ function as defined in the following table Specimens must be collected within 10 days prior to the start of study treatment.\n7. Histopathologically confirmed transitional cell carcinoma. Patients with mixed histologies are required to have a dominant (i.e. 50% at least) transitional cell pattern.\n8. Fit and planned for cystectomy (according to local guidelines).\n9. Clinical stage T2-T3a confirmed by TURB\n10. N0 M0 disease by CT (or MRI) + PET/CT (within 4 weeks of initial study treatment by RECIST v1.1).\nHealthy volunteers allowed\nMust have minimum age of 18 Years\nMust have maximum age of 99 Years",
        "exclusion_criteria": "1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.\n2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137, IDO1).\n3. Has received prior systemic anti-cancer therapy including investigational agents.\n4. Has received prior radiotherapy on the bladder tumor.\n5. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.\n6. Is currently participating in or has participated in a study of an investigational agent within 4 weeks prior to the first dose of study treatment.\n\n   Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.\n7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.\n8. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.\n\n   Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Participants with low-risk early stage prostate cancer defined as follows are not excluded; Stage T1c or T2a with a Gleason score ≤ 6 and prostatic-specific antigen (PSA) < 10 ng/mL either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study allocation.\n9. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.\n10. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.\n11. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.\n12. Has an active infection requiring systemic therapy.\n13. Has a known history of Human Immunodeficiency Virus (HIV).\n14. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.\n15. Has a known history of active TB (Bacillus Tuberculosis).\n16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.\n17. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.\n18. Pregnant or breastfeeding.\n19. Inability to swallow tablets or capsules",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial",
            "criterions": [
                {
                    "exact_snippets": "The participant (or legally acceptable representative if applicable) provides written informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Male/female participants who are at least 18 years of age will be enrolled in this study.",
            "criterions": [
                {
                    "exact_snippets": "Male/female participants",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "male",
                                "female"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "at least 18 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. A male participant must agree to use a contraception during the treatment period and for at least [120 days, corresponding to time needed to eliminate any study treatments) plus an additional 120 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose] after the last dose of study treatment and refrain from donating sperm during this period.",
            "criterions": [
                {
                    "exact_snippets": "A male participant",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "male"
                        }
                    ]
                },
                {
                    "exact_snippets": "must agree to use a contraception during the treatment period and for at least [120 days, corresponding to time needed to eliminate any study treatments) plus an additional 120 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose] after the last dose of study treatment",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "during the treatment period and for at least [120 days, corresponding to time needed to eliminate any study treatments) plus an additional 120 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose] after the last dose of study treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "refrain from donating sperm during this period",
                    "criterion": "sperm donation",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "refrain"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) or b.) A WOCBP who agrees to follow the contraceptive during the treatment period and for at least [120 days (corresponding to time needed to eliminate any study treatments) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity] after the last dose of study treatment.",
            "criterions": [
                {
                    "exact_snippets": "female participant",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": "female"
                        }
                    ]
                },
                {
                    "exact_snippets": "not pregnant",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "not breastfeeding",
                    "criterion": "breastfeeding status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Not a woman of childbearing potential (WOCBP)",
                    "criterion": "woman of childbearing potential status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "A WOCBP who agrees to follow the contraceptive during the treatment period and for at least [120 days ... plus 30 days ...] after the last dose of study treatment",
                    "criterion": "contraceptive use",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "during the treatment period and for at least 150 days after the last dose of study treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Have adequate organ function as defined in the following table Specimens must be collected within 10 days prior to the start of study treatment.",
            "criterions": [
                {
                    "exact_snippets": "adequate organ function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Histopathologically confirmed transitional cell carcinoma. Patients with mixed histologies are required to have a dominant (i.e. 50% at least) transitional cell pattern.",
            "criterions": [
                {
                    "exact_snippets": "Histopathologically confirmed transitional cell carcinoma",
                    "criterion": "transitional cell carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "histopathological"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients with mixed histologies ... dominant (i.e. 50% at least) transitional cell pattern",
                    "criterion": "mixed histologies",
                    "requirements": [
                        {
                            "requirement_type": "dominance",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Fit and planned for cystectomy (according to local guidelines).",
            "criterions": [
                {
                    "exact_snippets": "Fit",
                    "criterion": "fitness for surgery",
                    "requirements": [
                        {
                            "requirement_type": "fitness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "planned for cystectomy",
                    "criterion": "cystectomy plan",
                    "requirements": [
                        {
                            "requirement_type": "planned",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Clinical stage T2-T3a confirmed by TURB",
            "criterions": [
                {
                    "exact_snippets": "Clinical stage T2-T3a",
                    "criterion": "clinical stage",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 2,
                                        "unit": "T"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "T"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "confirmed by TURB",
                    "criterion": "confirmation method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "TURB"
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. N0 M0 disease by CT (or MRI) + PET/CT (within 4 weeks of initial study treatment by RECIST v1.1).",
            "criterions": [
                {
                    "exact_snippets": "N0 M0 disease",
                    "criterion": "disease stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "N0 M0"
                        }
                    ]
                },
                {
                    "exact_snippets": "CT (or MRI) + PET/CT",
                    "criterion": "imaging modality",
                    "requirements": [
                        {
                            "requirement_type": "modality",
                            "expected_value": [
                                "CT",
                                "MRI",
                                "PET/CT"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "within 4 weeks of initial study treatment",
                    "criterion": "imaging timing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "by RECIST v1.1",
                    "criterion": "evaluation criteria",
                    "requirements": [
                        {
                            "requirement_type": "criteria",
                            "expected_value": "RECIST v1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 99 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 99 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 99,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.",
            "criterions": [
                {
                    "exact_snippets": "WOCBP",
                    "criterion": "woman of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "positive urine pregnancy test within 72 hours prior to allocation",
                    "criterion": "urine pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "positive"
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 72 hours prior to allocation"
                        }
                    ]
                },
                {
                    "exact_snippets": "If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required",
                    "criterion": "serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": "required if urine test is positive or cannot be confirmed as negative"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137, IDO1).",
            "criterions": [
                {
                    "exact_snippets": "Has received prior therapy with an anti-PD-1",
                    "criterion": "prior therapy with anti-PD-1",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Has received prior therapy with an ... anti-PD-L1",
                    "criterion": "prior therapy with anti-PD-L1",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Has received prior therapy with an ... anti-PD-L2",
                    "criterion": "prior therapy with anti-PD-L2",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Has received prior therapy with an ... agent directed to another stimulatory or co-inhibitory T-cell receptor",
                    "criterion": "prior therapy with agent directed to stimulatory or co-inhibitory T-cell receptor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Has received prior therapy with an ... agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4",
                    "criterion": "prior therapy with agent directed to CTLA-4",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Has received prior therapy with an ... agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, ... OX-40",
                    "criterion": "prior therapy with agent directed to OX-40",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Has received prior therapy with an ... agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, ... CD137",
                    "criterion": "prior therapy with agent directed to CD137",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Has received prior therapy with an ... agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, ... IDO1",
                    "criterion": "prior therapy with agent directed to IDO1",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Has received prior systemic anti-cancer therapy including investigational agents.",
            "criterions": [
                {
                    "exact_snippets": "Has received prior systemic anti-cancer therapy including investigational agents.",
                    "criterion": "prior systemic anti-cancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "receipt",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Has received prior systemic anti-cancer therapy including investigational agents.",
                    "criterion": "investigational agents",
                    "requirements": [
                        {
                            "requirement_type": "receipt",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Has received prior radiotherapy on the bladder tumor.",
            "criterions": [
                {
                    "exact_snippets": "Has received prior radiotherapy on the bladder tumor.",
                    "criterion": "prior radiotherapy on the bladder tumor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.",
            "criterions": [
                {
                    "exact_snippets": "Has received a live vaccine within 30 days prior to the first dose of study drug.",
                    "criterion": "live vaccine administration",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.",
                    "criterion": "intranasal influenza vaccine",
                    "requirements": [
                        {
                            "requirement_type": "administration",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Is currently participating in or has participated in a study of an investigational agent within 4 weeks prior to the first dose of study treatment.",
            "criterions": [
                {
                    "exact_snippets": "currently participating in ... a study of an investigational agent",
                    "criterion": "participation in a study of an investigational agent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "has participated in a study of an investigational agent within 4 weeks prior to the first dose of study treatment",
                    "criterion": "participation in a study of an investigational agent",
                    "requirements": [
                        {
                            "requirement_type": "time since participation",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.",
            "criterions": [
                {
                    "exact_snippets": "Participants who have entered the follow-up phase of an investigational study",
                    "criterion": "participation in follow-up phase of investigational study",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "it has been 4 weeks after the last dose of the previous investigational agent",
                    "criterion": "time since last dose of investigational agent",
                    "requirements": [
                        {
                            "requirement_type": "time elapsed",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.",
            "criterions": [
                {
                    "exact_snippets": "Has a diagnosis of immunodeficiency",
                    "criterion": "immunodeficiency",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent)",
                    "criterion": "chronic systemic steroid therapy",
                    "requirements": [
                        {
                            "requirement_type": "dosing",
                            "expected_value": {
                                "operator": ">",
                                "value": 10,
                                "unit": "mg daily of prednisone equivalent"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug",
                    "criterion": "immunosuppressive therapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 7 days prior to the first dose of study drug"
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.",
            "criterions": [
                {
                    "exact_snippets": "Has a known additional malignancy",
                    "criterion": "additional malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "that is progressing",
                    "criterion": "additional malignancy progression",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "progressing"
                        }
                    ]
                },
                {
                    "exact_snippets": "or has required active treatment within the past 3 years",
                    "criterion": "additional malignancy treatment",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Participants with low-risk early stage prostate cancer defined as follows are not excluded; Stage T1c or T2a with a Gleason score ≤ 6 and prostatic-specific antigen (PSA) < 10 ng/mL either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study allocation.",
            "criterions": [
                {
                    "exact_snippets": "basal cell carcinoma of the skin",
                    "criterion": "basal cell carcinoma of the skin",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "potentially curative therapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "squamous cell carcinoma of the skin",
                    "criterion": "squamous cell carcinoma of the skin",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "potentially curative therapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "carcinoma in situ (eg, breast carcinoma, cervical cancer in situ)",
                    "criterion": "carcinoma in situ",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "potentially curative therapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "low-risk early stage prostate cancer",
                    "criterion": "low-risk early stage prostate cancer",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "Stage T1c or T2a"
                        },
                        {
                            "requirement_type": "Gleason score",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "N/A"
                            }
                        },
                        {
                            "requirement_type": "prostatic-specific antigen (PSA)",
                            "expected_value": {
                                "operator": "<",
                                "value": 10,
                                "unit": "ng/mL"
                            }
                        },
                        {
                            "requirement_type": "treatment",
                            "expected_value": [
                                "treated with definitive intent",
                                "untreated in active surveillance"
                            ]
                        },
                        {
                            "requirement_type": "stability",
                            "expected_value": "stable for the past year prior to study allocation"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.",
            "criterions": [
                {
                    "exact_snippets": "severe hypersensitivity (≥Grade 3) to pembrolizumab",
                    "criterion": "hypersensitivity to pembrolizumab",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "severe hypersensitivity (≥Grade 3) to ... any of its excipients",
                    "criterion": "hypersensitivity to pembrolizumab excipients",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "Grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.",
            "criterions": [
                {
                    "exact_snippets": "Has active autoimmune disease",
                    "criterion": "active autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "has required systemic treatment in the past 2 years",
                    "criterion": "systemic treatment for autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "past 2 years"
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.",
            "criterions": [
                {
                    "exact_snippets": "Has a history of (non-infectious) pneumonitis that required steroids",
                    "criterion": "history of non-infectious pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "steroids"
                        }
                    ]
                },
                {
                    "exact_snippets": "has current pneumonitis",
                    "criterion": "current pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Has an active infection requiring systemic therapy.",
            "criterions": [
                {
                    "exact_snippets": "active infection requiring systemic therapy",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        },
                        {
                            "requirement_type": "treatment",
                            "expected_value": "systemic therapy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Has a known history of Human Immunodeficiency Virus (HIV).",
            "criterions": [
                {
                    "exact_snippets": "known history of Human Immunodeficiency Virus (HIV)",
                    "criterion": "Human Immunodeficiency Virus (HIV)",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.",
            "criterions": [
                {
                    "exact_snippets": "known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive)",
                    "criterion": "Hepatitis B history",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection",
                    "criterion": "active Hepatitis C virus infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Has a known history of active TB (Bacillus Tuberculosis).",
            "criterions": [
                {
                    "exact_snippets": "known history of active TB (Bacillus Tuberculosis)",
                    "criterion": "active TB (Bacillus Tuberculosis)",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.",
            "criterions": [
                {
                    "exact_snippets": "Has a history or current evidence of any condition",
                    "criterion": "condition",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Has a history or current evidence of any ... therapy",
                    "criterion": "therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Has a history or current evidence of any ... laboratory abnormality",
                    "criterion": "laboratory abnormality",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.",
            "criterions": [
                {
                    "exact_snippets": "known psychiatric or substance abuse disorders",
                    "criterion": "psychiatric disorders",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "known psychiatric or substance abuse disorders",
                    "criterion": "substance abuse disorders",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "18. Pregnant or breastfeeding.",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breastfeeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "19. Inability to swallow tablets or capsules",
            "criterions": [
                {
                    "exact_snippets": "Inability to swallow tablets or capsules",
                    "criterion": "ability to swallow tablets or capsules",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}