{
    "info": {
        "nct_id": "NCT04895748",
        "official_title": "A Phase I/Ib, Open-label, Multi-center Study of DFF332 as a Single Agent and in Combination With Everolimus or IO Agents in Patients With Advanced/Relapsed ccRCC and Other Malignancies With HIF2α Stabilizing Mutations",
        "inclusion_criteria": "1. Male and female ≥ 18 years of age For Arm 1B: Male and female of age ≥ 12 years of age\n2. Histologically confirmed and documented clear cell renal cell carcinoma (ccRCC). Disease must be measurable as determined by RECIST v1.1.\n\n   For Arm 1B: histologically confirmed and documented malignancies in the context of the following cancer predisposing syndromes/disorders or harboring somatic mutations on one of these genes:\n   * Malignancies with VHL mutations (e.g. Von Hippel-Lindau disease)\n   * Malignancies with FH mutations (e.g. Hereditary leiomyomatosis and renal cell carcinoma)\n   * Malignancies with mutations in SDHD, SDHAF2, SDHC, SDHB, SDHA (e.g. Hereditary paraganglioma and pheochromocytoma syndrome)\n   * Malignancies with EPAS1/HIF2A mutations\n   * Malignancies with ELOC/TCEB1 mutations Note: Mutations must have been previously identified through local molecular assays.\n3. Patient with unresectable, locally advanced or metastatic ccRCC with documented disease progression following all standard of care therapy, including PD-1/L1 checkpoint inhibitor and a VEGF targeted therapy as monotherapy or in combination.\n\n   Escalation: No restriction on the number of prior treatments Expansion (with the exception of Arm 1B): Up to 3 prior lines of treatment for advanced/metastatic disease For Arm 1B: Patients must have either metastatic disease or locally advanced disease that is unresectable or that patients be unfit for resection or other treatment modalities. Patients must have received prior standard therapy appropriate for their tumor type and stage of disease, and have no available therapies of proven clinical benefit; or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.\n4. For patients age ≥ 16 years: ECOG performance status ≤ 1 For patients age ≥ 12 and < 16 years: Lansky performance status ≥ 70\nHealthy volunteers allowed\nMust have minimum age of 18 Years\nMust have maximum age of 100 Years",
        "exclusion_criteria": "1. History of seizure disorder & extrapyramidal (EPS) symptoms\n2. Impaired cardiac function or clinically significant cardiac disease, including any of the following:\n\n   * Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA Grade ≥ 2), uncontrolled hypertension\n   * Patients with corrected QT using the Fridericia's correction (QTcF) > 470 msec for all patients on screening ECG or congenital long QT syndrome Acute myocardial infarction or unstable angina < 3 months prior to study entry\n   * History of stroke or transient ischemic event requiring medical therapy\n   * Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker\n3. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes:\n\n   1. ≤ 4 weeks for radiation therapy or limited field radiation for palliation within ≤ 2 weeks prior to the first dose of study treatment.\n   2. ≤ 4 weeks or ≤ 5 half-lives (whichever is shorter) for chemotherapy or biological therapy (including monoclonal antibodies) or continuous or intermittent small molecule therapeutics or any other investigational agent.\n   3. ≤ 6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosourea and mitomycin C.\n   4. ≤ 4 weeks for immuno-oncologic therapy, such as CTLA-4, PD-1, or PD-L1 antagonists.\n   5. Patients who have undergone major surgery ≤ 4 weeks prior to first dose of study treatment or who have not recovered for the surgical procedure.\n4. Patient previously treated with a HIF2α inhibitor.\n5. Uncontrolled concurrent illness including, but not limited to, ongoing active infection, uncontrolled hypertension, active peptic ulcer disease or gastritis, active bleeding diatheses, including any Patient known to have evidence of acute or chronic hepatitis B, hepatitis C, human immunodeficency virus (HIV), or a psychiatric illness/social situation that in the investigator's opinion would limit compliance with study requirements or compromise the ability of the patient to give written informed consent. Patients with chronic HBV or HCV disease that is controlled under antiviral therapy are allowed in the expansion parts but not in the escalation parts.\n6. Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.\n7. Presence of Grade ≥ 2 toxicity according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAEv5.0), from prior cancer therapy with the exception of neuropathy (inclusion of patients with neuropathy of Grade 2 or less is permitted), ototoxicity, and alopecia.\n8. Pregnant or nursing (lactating) women\n\nOther protocol-defined inclusion/exclusion criteria may apply.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Male and female ≥ 18 years of age For Arm 1B: Male and female of age ≥ 12 years of age",
            "criterions": [
                {
                    "exact_snippets": "Male and female ≥ 18 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "For Arm 1B: Male and female of age ≥ 12 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Histologically confirmed and documented clear cell renal cell carcinoma (ccRCC). Disease must be measurable as determined by RECIST v1.1.",
            "criterions": [
                {
                    "exact_snippets": "Histologically confirmed and documented clear cell renal cell carcinoma (ccRCC)",
                    "criterion": "clear cell renal cell carcinoma (ccRCC)",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "histologically confirmed and documented"
                        }
                    ]
                },
                {
                    "exact_snippets": "Disease must be measurable as determined by RECIST v1.1",
                    "criterion": "disease measurability",
                    "requirements": [
                        {
                            "requirement_type": "measurement standard",
                            "expected_value": "RECIST v1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "For Arm 1B: histologically confirmed and documented malignancies in the context of the following cancer predisposing syndromes/disorders or harboring somatic mutations on one of these genes:",
            "criterions": [
                {
                    "exact_snippets": "histologically confirmed and documented malignancies",
                    "criterion": "malignancies",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "histologically confirmed"
                        },
                        {
                            "requirement_type": "documentation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "cancer predisposing syndromes/disorders",
                    "criterion": "cancer predisposing syndromes/disorders",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "harboring somatic mutations on one of these genes",
                    "criterion": "somatic mutations",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Malignancies with VHL mutations (e.g. Von Hippel-Lindau disease)",
            "criterions": [
                {
                    "exact_snippets": "Malignancies with VHL mutations",
                    "criterion": "VHL mutations",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Malignancies ... (e.g. Von Hippel-Lindau disease)",
                    "criterion": "Von Hippel-Lindau disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Malignancies with FH mutations (e.g. Hereditary leiomyomatosis and renal cell carcinoma)",
            "criterions": [
                {
                    "exact_snippets": "Malignancies with FH mutations",
                    "criterion": "FH mutations",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Malignancies with FH mutations (e.g. Hereditary leiomyomatosis and renal cell carcinoma)",
                    "criterion": "malignancies",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "Hereditary leiomyomatosis",
                                "renal cell carcinoma"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Malignancies with EPAS1/HIF2A mutations",
            "criterions": [
                {
                    "exact_snippets": "Malignancies with EPAS1/HIF2A mutations",
                    "criterion": "EPAS1/HIF2A mutations",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Malignancies with ELOC/TCEB1 mutations Note: Mutations must have been previously identified through local molecular assays.",
            "criterions": [
                {
                    "exact_snippets": "Malignancies with ELOC/TCEB1 mutations",
                    "criterion": "ELOC/TCEB1 mutations",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Mutations must have been previously identified through local molecular assays",
                    "criterion": "mutation identification",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "local molecular assays"
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patient with unresectable, locally advanced or metastatic ccRCC with documented disease progression following all standard of care therapy, including PD-1/L1 checkpoint inhibitor and a VEGF targeted therapy as monotherapy or in combination.",
            "criterions": [
                {
                    "exact_snippets": "unresectable, locally advanced or metastatic ccRCC",
                    "criterion": "ccRCC",
                    "requirements": [
                        {
                            "requirement_type": "resectability",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "locally advanced",
                                "metastatic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "documented disease progression",
                    "criterion": "disease progression",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "following all standard of care therapy, including PD-1/L1 checkpoint inhibitor and a VEGF targeted therapy",
                    "criterion": "standard of care therapy",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "inclusion",
                            "expected_value": [
                                "PD-1/L1 checkpoint inhibitor",
                                "VEGF targeted therapy"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "Escalation: No restriction on the number of prior treatments Expansion (with the exception of Arm 1B): Up to 3 prior lines of treatment for advanced/metastatic disease For Arm 1B: Patients must have either metastatic disease or locally advanced disease that is unresectable or that patients be unfit for resection or other treatment modalities. Patients must have received prior standard therapy appropriate for their tumor type and stage of disease, and have no available therapies of proven clinical benefit; or in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.",
            "criterions": [
                {
                    "exact_snippets": "Escalation: No restriction on the number of prior treatments",
                    "criterion": "number of prior treatments",
                    "requirements": [
                        {
                            "requirement_type": "restriction",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Expansion (with the exception of Arm 1B): Up to 3 prior lines of treatment for advanced/metastatic disease",
                    "criterion": "prior lines of treatment",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "lines"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "For Arm 1B: Patients must have either metastatic disease or locally advanced disease that is unresectable",
                    "criterion": "disease status",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "metastatic",
                                "locally advanced"
                            ]
                        },
                        {
                            "requirement_type": "resectability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "For Arm 1B: ... or that patients be unfit for resection or other treatment modalities.",
                    "criterion": "fitness for resection or other treatment modalities",
                    "requirements": [
                        {
                            "requirement_type": "fitness",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients must have received prior standard therapy appropriate for their tumor type and stage of disease",
                    "criterion": "prior standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "receipt",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "have no available therapies of proven clinical benefit",
                    "criterion": "availability of therapies of proven clinical benefit",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "in the opinion of the investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy",
                    "criterion": "tolerance or benefit from standard of care therapy",
                    "requirements": [
                        {
                            "requirement_type": "likelihood",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. For patients age ≥ 16 years: ECOG performance status ≤ 1 For patients age ≥ 12 and < 16 years: Lansky performance status ≥ 70",
            "criterions": [
                {
                    "exact_snippets": "patients age ≥ 16 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 16,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patients age ≥ 16 years: ECOG performance status ≤ 1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patients age ≥ 12 and < 16 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 12,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<",
                                        "value": 16,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patients age ≥ 12 and < 16 years: Lansky performance status ≥ 70",
                    "criterion": "Lansky performance status",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 70,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "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 100 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 100 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 100,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. History of seizure disorder & extrapyramidal (EPS) symptoms",
            "criterions": [
                {
                    "exact_snippets": "History of seizure disorder",
                    "criterion": "seizure disorder",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "extrapyramidal (EPS) symptoms",
                    "criterion": "extrapyramidal symptoms",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Impaired cardiac function or clinically significant cardiac disease, including any of the following:",
            "criterions": [
                {
                    "exact_snippets": "Impaired cardiac function",
                    "criterion": "cardiac function",
                    "requirements": [
                        {
                            "requirement_type": "impairment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically significant cardiac disease",
                    "criterion": "cardiac disease",
                    "requirements": [
                        {
                            "requirement_type": "clinical significance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA Grade ≥ 2), uncontrolled hypertension",
            "criterions": [
                {
                    "exact_snippets": "Clinically significant and/or uncontrolled heart disease",
                    "criterion": "heart disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "clinically significant"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "congestive heart failure requiring treatment (NYHA Grade ≥ 2)",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "NYHA Grade",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled hypertension",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with corrected QT using the Fridericia's correction (QTcF) > 470 msec for all patients on screening ECG or congenital long QT syndrome Acute myocardial infarction or unstable angina < 3 months prior to study entry",
            "criterions": [
                {
                    "exact_snippets": "corrected QT using the Fridericia's correction (QTcF) > 470 msec",
                    "criterion": "QTcF",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 470,
                                "unit": "msec"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "congenital long QT syndrome",
                    "criterion": "congenital long QT syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Acute myocardial infarction ... < 3 months prior to study entry",
                    "criterion": "acute myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable angina < 3 months prior to study entry",
                    "criterion": "unstable angina",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of stroke or transient ischemic event requiring medical therapy",
            "criterions": [
                {
                    "exact_snippets": "History of stroke",
                    "criterion": "stroke",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "transient ischemic event requiring medical therapy",
                    "criterion": "transient ischemic event",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "medical therapy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker",
            "criterions": [
                {
                    "exact_snippets": "Concomitant clinically significant cardiac arrhythmias",
                    "criterion": "cardiac arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically significant second or third degree AV block without a pacemaker",
                    "criterion": "second or third degree AV block",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "pacemaker",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes:",
            "criterions": [
                {
                    "exact_snippets": "Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment",
                    "criterion": "prior anti-cancer therapies",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. ≤ 4 weeks for radiation therapy or limited field radiation for palliation within ≤ 2 weeks prior to the first dose of study treatment.",
            "criterions": [
                {
                    "exact_snippets": "≤ 4 weeks for radiation therapy",
                    "criterion": "radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "limited field radiation for palliation within ≤ 2 weeks",
                    "criterion": "limited field radiation for palliation",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. ≤ 4 weeks or ≤ 5 half-lives (whichever is shorter) for chemotherapy or biological therapy (including monoclonal antibodies) or continuous or intermittent small molecule therapeutics or any other investigational agent.",
            "criterions": [
                {
                    "exact_snippets": "≤ 4 weeks or ≤ 5 half-lives (whichever is shorter) for chemotherapy",
                    "criterion": "chemotherapy washout period",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "≤ 4 weeks or ≤ 5 half-lives (whichever is shorter) for ... biological therapy (including monoclonal antibodies)",
                    "criterion": "biological therapy washout period",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "≤ 4 weeks or ≤ 5 half-lives (whichever is shorter) for ... continuous or intermittent small molecule therapeutics",
                    "criterion": "small molecule therapeutics washout period",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "≤ 4 weeks or ≤ 5 half-lives (whichever is shorter) for ... any other investigational agent",
                    "criterion": "investigational agent washout period",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. ≤ 6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosourea and mitomycin C.",
            "criterions": [
                {
                    "exact_snippets": "≤ 6 weeks for cytotoxic agents with major delayed toxicities",
                    "criterion": "cytotoxic agent washout period",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. ≤ 4 weeks for immuno-oncologic therapy, such as CTLA-4, PD-1, or PD-L1 antagonists.",
            "criterions": [
                {
                    "exact_snippets": "≤ 4 weeks for immuno-oncologic therapy, such as CTLA-4, PD-1, or PD-L1 antagonists.",
                    "criterion": "immuno-oncologic therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        },
                        {
                            "requirement_type": "therapy type",
                            "expected_value": [
                                "CTLA-4",
                                "PD-1",
                                "PD-L1 antagonists"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Patients who have undergone major surgery ≤ 4 weeks prior to first dose of study treatment or who have not recovered for the surgical procedure.",
            "criterions": [
                {
                    "exact_snippets": "undergone major surgery ≤ 4 weeks prior to first dose of study treatment",
                    "criterion": "time since major surgery",
                    "requirements": [
                        {
                            "requirement_type": "time since surgery",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "who have not recovered for the surgical procedure",
                    "criterion": "recovery from surgery",
                    "requirements": [
                        {
                            "requirement_type": "recovery status",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Patient previously treated with a HIF2α inhibitor.",
            "criterions": [
                {
                    "exact_snippets": "Patient previously treated with a HIF2α inhibitor.",
                    "criterion": "HIF2α inhibitor treatment",
                    "requirements": [
                        {
                            "requirement_type": "treatment history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Uncontrolled concurrent illness including, but not limited to, ongoing active infection, uncontrolled hypertension, active peptic ulcer disease or gastritis, active bleeding diatheses, including any Patient known to have evidence of acute or chronic hepatitis B, hepatitis C, human immunodeficency virus (HIV), or a psychiatric illness/social situation that in the investigator's opinion would limit compliance with study requirements or compromise the ability of the patient to give written informed consent. Patients with chronic HBV or HCV disease that is controlled under antiviral therapy are allowed in the expansion parts but not in the escalation parts.",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled concurrent illness including, but not limited to, ongoing active infection",
                    "criterion": "concurrent illness",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "ongoing active infection",
                    "criterion": "active infection",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "ongoing"
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled hypertension",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "active peptic ulcer disease or gastritis",
                    "criterion": "peptic ulcer disease or gastritis",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "active bleeding diatheses",
                    "criterion": "bleeding diatheses",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "evidence of acute or chronic hepatitis B",
                    "criterion": "hepatitis B",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "evidence of acute or chronic ... hepatitis C",
                    "criterion": "hepatitis C",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "evidence of acute or chronic ... human immunodeficency virus (HIV)",
                    "criterion": "HIV",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "psychiatric illness/social situation that in the investigator's opinion would limit compliance with study requirements or compromise the ability of the patient to give written informed consent",
                    "criterion": "psychiatric illness/social situation",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance or consent",
                            "expected_value": "would limit compliance or compromise consent"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients with chronic HBV or HCV disease that is controlled under antiviral therapy are allowed in the expansion parts but not in the escalation parts",
                    "criterion": "chronic HBV or HCV disease",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "controlled under antiviral therapy"
                        },
                        {
                            "requirement_type": "trial part",
                            "expected_value": "allowed in expansion, not in escalation"
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.",
            "criterions": [
                {
                    "exact_snippets": "Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.",
                    "criterion": "live vaccines",
                    "requirements": [
                        {
                            "requirement_type": "use",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Presence of Grade ≥ 2 toxicity according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAEv5.0), from prior cancer therapy with the exception of neuropathy (inclusion of patients with neuropathy of Grade 2 or less is permitted), ototoxicity, and alopecia.",
            "criterions": [
                {
                    "exact_snippets": "Presence of Grade ≥ 2 toxicity according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAEv5.0), from prior cancer therapy",
                    "criterion": "toxicity from prior cancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "exception of neuropathy (inclusion of patients with neuropathy of Grade 2 or less is permitted)",
                    "criterion": "neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "exception of ... ototoxicity",
                    "criterion": "ototoxicity",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "exception of ... alopecia",
                    "criterion": "alopecia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Pregnant or nursing (lactating) women",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "nursing (lactating)",
                    "criterion": "nursing status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "Other protocol-defined inclusion/exclusion criteria may apply.",
            "criterions": [
                {
                    "exact_snippets": "Other protocol-defined inclusion/exclusion criteria",
                    "criterion": "protocol-defined criteria",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "* Malignancies with mutations in SDHD, SDHAF2, SDHC, SDHB, SDHA (e.g. Hereditary paraganglioma and pheochromocytoma syndrome)",
            "criterions": [
                {
                    "exact_snippets": "Malignancies with mutations in SDHD",
                    "criterion": "SDHD mutation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Malignancies with mutations in SDHAF2",
                    "criterion": "SDHAF2 mutation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Malignancies with mutations in SDHC",
                    "criterion": "SDHC mutation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Malignancies with mutations in SDHB",
                    "criterion": "SDHB mutation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Malignancies with mutations in SDHA",
                    "criterion": "SDHA mutation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}