{
    "info": {
        "nct_id": "NCT04794972",
        "official_title": "An Open-Label, Multi-Center, Phase I Study to Evaluate the Safety, Tolerability，Pharmacokinetic/Pharmacodynamics and Anti-tumor Activity of Tetra-specific Antibody GNC-039 in Participants With Relapsed/Refractory or Metastatic Solid Tumors",
        "inclusion_criteria": "1. After failure of standard treatment (surgery, stupp regimen), subjects with diagnosed recurrent high-grade glioma (WHO Grade III-IV), or other recurrent/refractory or metastatic solid tumors can understand the informed consent, voluntarily participate in and sign the informed consent.\n2. No gender limitation.\n3. Age: ≥18 years old.\n4. KPS≥60 points.\n5. The expected survival as determined by the researchers was ≥3 months.\n6. Hematological functions meet the following requirements: neutrophil absolute count (ANC) ≥1.5×109/L, platelet count ≥75×109/L, hemoglobin ≥90g/L.\n7. Renal function meets the following requirements: creatinine (Cr) ≤1.5 ULN and creatinine clearance (Ccr) ≥50 mL/min (based on the calculation criteria of the study center), urinary protein ≤2+ or < 1000mg/24h (urine).\n8. Liver functions meet the following requirements: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0×ULN; Total bilirubin ≤1.5×ULN (Gilbert's syndrome ≤3×ULN).\n9. Coagulation function: fibrinogen ≥1.5g/L; Activated partial thromboplastin time (APTT) ≤1.5×ULN; Prothrombin time (PT) ≤1.5×ULN.\n10. A fertile female subject or a fertile male subject with a fertile partner must use highly effective contraception from the date of informed consent until 12 weeks after the last dosing. Serum pregnancy tests must be negative for fertile female subjects within -10 to -3 days prior to initial dosing.\n11. Subject is able and willing to comply with visits, treatment plans, laboratory tests, and other study-related procedures as specified in the study protocol.\n12. For glioma patients: a. There must be a pathological diagnosis and a definite diagnosis of high-grade glioma; b. MRI diagnosis supported recurrence; c. Presence of at least one measurable tumor lesion according to RANO criteria; Or subjects receiving surgical treatment after recurrence; d. Archived primary or recurrent tumor tissue or sections that can be submitted to the Center for review (no less than 10 pathological white slices of 3-5μm or corresponding tissue blocks should be provided). If patients are unable to provide tumor tissue specimens, the Center may inform the sponsor and enroll them.\n13. For patients with other solid tumors: a. Histologically or cytologically confirmed recurrent/refractory or metastatic solid tumors with disease progression confirmed by imaging or other objective evidence after standard treatment; Or subjects with refractory solid tumors who cannot tolerate standard therapy or have contraindications to standard therapy; b. Must have at least one measurable lesion that meets the RECIST v1.1 definition.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Patients who are allergic to immunoglobulin or any component of the injectable formulation of GNC-039.\n2. Patients with active infections requiring intravenous antibiotics who did not complete treatment 1 week prior to enrollment, except those who received prophylactic antibiotics for puncture or biopsy.\n3. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBsAg positive or HBcAb positive with HBV-DNA copy number ≥ULN) or hepatitis C virus infection (HCV-RNA≥ULN).\n4. Toxicity from prior antitumor therapy did not decrease to ≤ grade 1 as defined in CTCAE version 5.0 (except for toxicities that the investigators judged to be of no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, stable hypothyroidism after hormone replacement therapy, etc.).\n5. Patients at risk for active autoimmune diseases, or with a history of autoimmune diseases that may involve the central nervous system, Including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, Wegener syndrome, autoimmune hepatitis, systemic sclerosis, Hashimoto's thyroiditis, autoimmune vasculitis, autoimmune neuropathy (Guillain-Barre syndrome), etc. Exceptions include type I diabetes mellitus, hypothyroidism stable on hormone replacement therapy (including hypothyroidism caused by autoimmune thyroid disease), psoriasis or vitiligo that do not require systemic therapy, and autoimmune diseases caused by B cells and anti-autoimmune antibodies.\n6. Lung disease defined by NCI-CTCAE v5.0 as ≥ grade 3, including patients with resting dyspnea, or in need of continuous oxygen therapy, or with a history of interstitial lung disease (ILD).\n7. Previous organ transplant recipients.\n8. History of severe cardiovascular and cerebrovascular diseases, including but not limited to: severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, degree III atrioventricular block, etc.; At rest, the QT interval was prolonged (QTc > 450 msec in men or 470 msec in women); Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months prior to initial administration; There is heart failure ≥II on the New York Heart Association (NYHA) cardiac function scale.\n9. Thrombotic events such as deep vein thrombosis, arterial thrombosis, and pulmonary embolism occurred within 6 months prior to screening.\n10. Other conditions deemed unsuitable for participation in this clinical trial by the investigator.\n11. Brain gliomas: a. Patients who underwent surgery, chemotherapy, targeted and immunotherapy, iodine in vivo radiation, radiation therapy, or planned to undergo radiation therapy during the trial within 4 weeks of enrollment or 5 half-lives, whichever is shorter; b. Patients who had received intracranial lesion puncture biopsy within 7 days prior to enrollment; c. Received other investigational drugs or treatments that are not on the market within 4 weeks prior to enrollment; d. There was a history of central nervous system bleeding/infarction not associated with antineoplastic agents, such as stroke or intracranial and ocular bleeding (including embolic stroke), during the 6 months prior to enrollment.\n12. For other solid tumors: a. Received chemotherapy, antibody therapy, molecular-targeted therapy, or investigational drugs within 4 weeks or 5 half-lives (whichever is shorter) of initial administration; b. Patients who underwent major surgery within 28 days prior to administration of the drug or were scheduled to undergo major surgery during the study period (except for procedures such as puncture or lymph node biopsy); c. poorly controlled hypertension (systolic blood pressure &gt; 150 mmHg or diastolic blood pressure &gt; 100 mmHg); d. Previous or associated central nervous system lesions, including but not limited to: paralysis, stroke (except those with lacunar infarction indicated by imaging examination but without treatment), severe brain injury, senile dementia, Parkinson's disease, organic brain syndrome, and psychosis; e. Received other investigational drugs or treatments that were not on the market within 4 weeks prior to enrollment.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. After failure of standard treatment (surgery, stupp regimen), subjects with diagnosed recurrent high-grade glioma (WHO Grade III-IV), or other recurrent/refractory or metastatic solid tumors can understand the informed consent, voluntarily participate in and sign the informed consent.",
            "criterions": [
                {
                    "exact_snippets": "failure of standard treatment (surgery, stupp regimen)",
                    "criterion": "standard treatment failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "diagnosed recurrent high-grade glioma (WHO Grade III-IV)",
                    "criterion": "recurrent high-grade glioma",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "other recurrent/refractory or metastatic solid tumors",
                    "criterion": "recurrent/refractory or metastatic solid tumors",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "can understand the informed consent",
                    "criterion": "understanding of informed consent",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "voluntarily participate in and sign the informed consent",
                    "criterion": "voluntary participation and consent",
                    "requirements": [
                        {
                            "requirement_type": "action",
                            "expected_value": "sign the informed consent"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. No gender limitation.",
            "criterions": [
                {
                    "exact_snippets": "No gender limitation.",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "limitation",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Age: ≥18 years old.",
            "criterions": [
                {
                    "exact_snippets": "Age: ≥18 years old.",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. KPS≥60 points.",
            "criterions": [
                {
                    "exact_snippets": "KPS≥60 points.",
                    "criterion": "Karnofsky Performance Status (KPS)",
                    "requirements": [
                        {
                            "requirement_type": "score",
                            "expected_value": {
                                "operator": ">=",
                                "value": 60,
                                "unit": "points"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. The expected survival as determined by the researchers was ≥3 months.",
            "criterions": [
                {
                    "exact_snippets": "expected survival ... ≥3 months",
                    "criterion": "expected survival",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Hematological functions meet the following requirements: neutrophil absolute count (ANC) ≥1.5×109/L, platelet count ≥75×109/L, hemoglobin ≥90g/L.",
            "criterions": [
                {
                    "exact_snippets": "neutrophil absolute count (ANC) ≥1.5×109/L",
                    "criterion": "neutrophil absolute count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "×10^9/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "platelet count ≥75×109/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 75,
                                "unit": "×10^9/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "hemoglobin ≥90g/L",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 90,
                                "unit": "g/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Renal function meets the following requirements: creatinine (Cr) ≤1.5 ULN and creatinine clearance (Ccr) ≥50 mL/min (based on the calculation criteria of the study center), urinary protein ≤2+ or < 1000mg/24h (urine).",
            "criterions": [
                {
                    "exact_snippets": "Renal function meets the following requirements: creatinine (Cr) ≤1.5 ULN",
                    "criterion": "creatinine (Cr)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinine clearance (Ccr) ≥50 mL/min",
                    "criterion": "creatinine clearance (Ccr)",
                    "requirements": [
                        {
                            "requirement_type": "rate",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "mL/min"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "urinary protein ≤2+ or < 1000mg/24h (urine)",
                    "criterion": "urinary protein",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": [
                                "≤2+",
                                "< 1000mg/24h"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Liver functions meet the following requirements: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0×ULN; Total bilirubin ≤1.5×ULN (Gilbert's syndrome ≤3×ULN).",
            "criterions": [
                {
                    "exact_snippets": "Aspartate aminotransferase (AST) ... ≤3.0×ULN",
                    "criterion": "Aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3.0,
                                "unit": "ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alanine aminotransferase (ALT) ≤3.0×ULN",
                    "criterion": "alanine aminotransferase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3.0,
                                "unit": "ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Total bilirubin ≤1.5×ULN",
                    "criterion": "Total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Gilbert's syndrome ≤3×ULN",
                    "criterion": "Gilbert's syndrome",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Coagulation function: fibrinogen ≥1.5g/L; Activated partial thromboplastin time (APTT) ≤1.5×ULN; Prothrombin time (PT) ≤1.5×ULN.",
            "criterions": [
                {
                    "exact_snippets": "Coagulation function: fibrinogen ≥1.5g/L",
                    "criterion": "fibrinogen",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "g/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Activated partial thromboplastin time (APTT) ≤1.5×ULN",
                    "criterion": "Activated partial thromboplastin time (APTT)",
                    "requirements": [
                        {
                            "requirement_type": "time",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "×ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Prothrombin time (PT) ≤1.5×ULN",
                    "criterion": "Prothrombin time (PT)",
                    "requirements": [
                        {
                            "requirement_type": "time",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "×ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. A fertile female subject or a fertile male subject with a fertile partner must use highly effective contraception from the date of informed consent until 12 weeks after the last dosing. Serum pregnancy tests must be negative for fertile female subjects within -10 to -3 days prior to initial dosing.",
            "criterions": [
                {
                    "exact_snippets": "A fertile female subject or a fertile male subject with a fertile partner must use highly effective contraception",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Serum pregnancy tests must be negative for fertile female subjects",
                    "criterion": "serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "within -10 to -3 days prior to initial dosing",
                    "criterion": "serum pregnancy test timing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": -10,
                                        "unit": "days"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": -3,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Subject is able and willing to comply with visits, treatment plans, laboratory tests, and other study-related procedures as specified in the study protocol.",
            "criterions": [
                {
                    "exact_snippets": "Subject is able and willing to comply with visits",
                    "criterion": "compliance with visits",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Subject is able and willing to comply with ... treatment plans",
                    "criterion": "compliance with treatment plans",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Subject is able and willing to comply with ... laboratory tests",
                    "criterion": "compliance with laboratory tests",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Subject is able and willing to comply with ... other study-related procedures",
                    "criterion": "compliance with other study-related procedures",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. For glioma patients: a. There must be a pathological diagnosis and a definite diagnosis of high-grade glioma; b. MRI diagnosis supported recurrence; c. Presence of at least one measurable tumor lesion according to RANO criteria; Or subjects receiving surgical treatment after recurrence; d. Archived primary or recurrent tumor tissue or sections that can be submitted to the Center for review (no less than 10 pathological white slices of 3-5μm or corresponding tissue blocks should be provided). If patients are unable to provide tumor tissue specimens, the Center may inform the sponsor and enroll them.",
            "criterions": [
                {
                    "exact_snippets": "pathological diagnosis",
                    "criterion": "pathological diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "definite diagnosis of high-grade glioma",
                    "criterion": "high-grade glioma diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "certainty",
                            "expected_value": "definite"
                        }
                    ]
                },
                {
                    "exact_snippets": "MRI diagnosis supported recurrence",
                    "criterion": "recurrence",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis method",
                            "expected_value": "MRI"
                        }
                    ]
                },
                {
                    "exact_snippets": "Presence of at least one measurable tumor lesion according to RANO criteria",
                    "criterion": "measurable tumor lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        },
                        {
                            "requirement_type": "measurement criteria",
                            "expected_value": "RANO"
                        }
                    ]
                },
                {
                    "exact_snippets": "subjects receiving surgical treatment after recurrence",
                    "criterion": "surgical treatment after recurrence",
                    "requirements": [
                        {
                            "requirement_type": "treatment type",
                            "expected_value": "surgical"
                        }
                    ]
                },
                {
                    "exact_snippets": "Archived primary or recurrent tumor tissue or sections that can be submitted to the Center for review",
                    "criterion": "tumor tissue submission",
                    "requirements": [
                        {
                            "requirement_type": "submission",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "no less than 10 pathological white slices of 3-5μm or corresponding tissue blocks should be provided",
                    "criterion": "tumor tissue slices",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 10,
                                "unit": "slices"
                            }
                        },
                        {
                            "requirement_type": "slice thickness",
                            "expected_value": {
                                "operator": "=",
                                "value": 3,
                                "unit": "μm"
                            }
                        },
                        {
                            "requirement_type": "slice thickness",
                            "expected_value": {
                                "operator": "=",
                                "value": 5,
                                "unit": "μm"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. For patients with other solid tumors: a. Histologically or cytologically confirmed recurrent/refractory or metastatic solid tumors with disease progression confirmed by imaging or other objective evidence after standard treatment; Or subjects with refractory solid tumors who cannot tolerate standard therapy or have contraindications to standard therapy; b. Must have at least one measurable lesion that meets the RECIST v1.1 definition.",
            "criterions": [
                {
                    "exact_snippets": "Histologically or cytologically confirmed recurrent/refractory or metastatic solid tumors",
                    "criterion": "solid tumors",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        },
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "recurrent",
                                "refractory",
                                "metastatic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "disease progression confirmed by imaging or other objective evidence after standard treatment",
                    "criterion": "disease progression",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": [
                                "imaging",
                                "other objective evidence"
                            ]
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "after standard treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "subjects with refractory solid tumors who cannot tolerate standard therapy or have contraindications to standard therapy",
                    "criterion": "refractory solid tumors",
                    "requirements": [
                        {
                            "requirement_type": "tolerance to standard therapy",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "contraindications to standard therapy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Must have at least one measurable lesion that meets the RECIST v1.1 definition",
                    "criterion": "measurable lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        },
                        {
                            "requirement_type": "definition",
                            "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"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Patients who are allergic to immunoglobulin or any component of the injectable formulation of GNC-039.",
            "criterions": [
                {
                    "exact_snippets": "Patients who are allergic to immunoglobulin",
                    "criterion": "allergy to immunoglobulin",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "allergic to ... any component of the injectable formulation of GNC-039",
                    "criterion": "allergy to components of GNC-039",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Patients with active infections requiring intravenous antibiotics who did not complete treatment 1 week prior to enrollment, except those who received prophylactic antibiotics for puncture or biopsy.",
            "criterions": [
                {
                    "exact_snippets": "active infections requiring intravenous antibiotics",
                    "criterion": "active infections",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "intravenous antibiotics"
                        }
                    ]
                },
                {
                    "exact_snippets": "did not complete treatment 1 week prior to enrollment",
                    "criterion": "treatment completion",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "week"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except those who received prophylactic antibiotics for puncture or biopsy",
                    "criterion": "prophylactic antibiotics",
                    "requirements": [
                        {
                            "requirement_type": "purpose",
                            "expected_value": [
                                "puncture",
                                "biopsy"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBsAg positive or HBcAb positive with HBV-DNA copy number ≥ULN) or hepatitis C virus infection (HCV-RNA≥ULN).",
            "criterions": [
                {
                    "exact_snippets": "Human immunodeficiency virus antibody (HIVAb) positive",
                    "criterion": "HIV antibody",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active tuberculosis",
                    "criterion": "tuberculosis",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "active hepatitis B virus infection (HBsAg positive or HBcAb positive with HBV-DNA copy number ≥ULN)",
                    "criterion": "hepatitis B virus infection",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        },
                        {
                            "requirement_type": "HBsAg presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "HBcAb presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "HBV-DNA copy number",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "hepatitis C virus infection (HCV-RNA≥ULN)",
                    "criterion": "hepatitis C virus infection",
                    "requirements": [
                        {
                            "requirement_type": "HCV-RNA level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Toxicity from prior antitumor therapy did not decrease to ≤ grade 1 as defined in CTCAE version 5.0 (except for toxicities that the investigators judged to be of no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, stable hypothyroidism after hormone replacement therapy, etc.).",
            "criterions": [
                {
                    "exact_snippets": "Toxicity from prior antitumor therapy did not decrease to ≤ grade 1 as defined in CTCAE version 5.0",
                    "criterion": "toxicity from prior antitumor therapy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "toxicities that the investigators judged to be of no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, stable hypothyroidism after hormone replacement therapy",
                    "criterion": "toxicity exceptions",
                    "requirements": [
                        {
                            "requirement_type": "safety risk",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Patients at risk for active autoimmune diseases, or with a history of autoimmune diseases that may involve the central nervous system, Including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, Wegener syndrome, autoimmune hepatitis, systemic sclerosis, Hashimoto's thyroiditis, autoimmune vasculitis, autoimmune neuropathy (Guillain-Barre syndrome), etc. Exceptions include type I diabetes mellitus, hypothyroidism stable on hormone replacement therapy (including hypothyroidism caused by autoimmune thyroid disease), psoriasis or vitiligo that do not require systemic therapy, and autoimmune diseases caused by B cells and anti-autoimmune antibodies.",
            "criterions": [
                {
                    "exact_snippets": "Patients at risk for active autoimmune diseases",
                    "criterion": "risk for active autoimmune diseases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "history of autoimmune diseases that may involve the central nervous system",
                    "criterion": "history of autoimmune diseases involving the central nervous system",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Crohn's disease",
                    "criterion": "Crohn's disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "ulcerative colitis",
                    "criterion": "ulcerative colitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "systemic lupus erythematosus",
                    "criterion": "systemic lupus erythematosus",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Wegener syndrome",
                    "criterion": "Wegener syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "autoimmune hepatitis",
                    "criterion": "autoimmune hepatitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "systemic sclerosis",
                    "criterion": "systemic sclerosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Hashimoto's thyroiditis",
                    "criterion": "Hashimoto's thyroiditis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "autoimmune vasculitis",
                    "criterion": "autoimmune vasculitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "autoimmune neuropathy (Guillain-Barre syndrome)",
                    "criterion": "autoimmune neuropathy (Guillain-Barre syndrome)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Exceptions include type I diabetes mellitus",
                    "criterion": "type I diabetes mellitus",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hypothyroidism stable on hormone replacement therapy",
                    "criterion": "hypothyroidism stable on hormone replacement therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "psoriasis or vitiligo that do not require systemic therapy",
                    "criterion": "psoriasis or vitiligo not requiring systemic therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "autoimmune diseases caused by B cells and anti-autoimmune antibodies",
                    "criterion": "autoimmune diseases caused by B cells and anti-autoimmune antibodies",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Lung disease defined by NCI-CTCAE v5.0 as ≥ grade 3, including patients with resting dyspnea, or in need of continuous oxygen therapy, or with a history of interstitial lung disease (ILD).",
            "criterions": [
                {
                    "exact_snippets": "Lung disease defined by NCI-CTCAE v5.0 as ≥ grade 3",
                    "criterion": "lung disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with resting dyspnea",
                    "criterion": "resting dyspnea",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "in need of continuous oxygen therapy",
                    "criterion": "continuous oxygen therapy",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of interstitial lung disease (ILD)",
                    "criterion": "interstitial lung disease (ILD)",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Previous organ transplant recipients.",
            "criterions": [
                {
                    "exact_snippets": "Previous organ transplant recipients",
                    "criterion": "organ transplant",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. History of severe cardiovascular and cerebrovascular diseases, including but not limited to: severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, degree III atrioventricular block, etc.; At rest, the QT interval was prolonged (QTc > 450 msec in men or 470 msec in women); Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months prior to initial administration; There is heart failure ≥II on the New York Heart Association (NYHA) cardiac function scale.",
            "criterions": [
                {
                    "exact_snippets": "History of severe cardiovascular and cerebrovascular diseases",
                    "criterion": "severe cardiovascular and cerebrovascular diseases",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "severe cardiac rhythm or conduction abnormalities",
                    "criterion": "severe cardiac rhythm or conduction abnormalities",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ventricular arrhythmia requiring clinical intervention",
                    "criterion": "ventricular arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "requiring clinical intervention"
                        }
                    ]
                },
                {
                    "exact_snippets": "degree III atrioventricular block",
                    "criterion": "degree III atrioventricular block",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "QT interval was prolonged (QTc > 450 msec in men or 470 msec in women)",
                    "criterion": "QT interval",
                    "requirements": [
                        {
                            "requirement_type": "prolongation",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">",
                                        "value": 450,
                                        "unit": "msec"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "prolongation",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">",
                                        "value": 470,
                                        "unit": "msec"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Acute coronary syndrome",
                    "criterion": "acute coronary syndrome",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": "within 6 months prior to initial administration"
                        }
                    ]
                },
                {
                    "exact_snippets": "congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": "within 6 months prior to initial administration"
                        }
                    ]
                },
                {
                    "exact_snippets": "aortic dissection",
                    "criterion": "aortic dissection",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": "within 6 months prior to initial administration"
                        }
                    ]
                },
                {
                    "exact_snippets": "stroke",
                    "criterion": "stroke",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": "within 6 months prior to initial administration"
                        }
                    ]
                },
                {
                    "exact_snippets": "other grade 3 or higher cardiovascular and cerebrovascular events",
                    "criterion": "grade 3 or higher cardiovascular and cerebrovascular events",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": "within 6 months prior to initial administration"
                        }
                    ]
                },
                {
                    "exact_snippets": "heart failure ≥II on the New York Heart Association (NYHA) cardiac function scale",
                    "criterion": "heart failure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 2,
                                        "unit": "NYHA scale"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Thrombotic events such as deep vein thrombosis, arterial thrombosis, and pulmonary embolism occurred within 6 months prior to screening.",
            "criterions": [
                {
                    "exact_snippets": "Thrombotic events such as deep vein thrombosis",
                    "criterion": "deep vein thrombosis",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months prior to screening"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Thrombotic events such as ... arterial thrombosis",
                    "criterion": "arterial thrombosis",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months prior to screening"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Thrombotic events such as ... pulmonary embolism",
                    "criterion": "pulmonary embolism",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months prior to screening"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Other conditions deemed unsuitable for participation in this clinical trial by the investigator.",
            "criterions": [
                {
                    "exact_snippets": "Other conditions deemed unsuitable for participation ... by the investigator.",
                    "criterion": "other conditions",
                    "requirements": [
                        {
                            "requirement_type": "suitability",
                            "expected_value": "deemed unsuitable by the investigator"
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Brain gliomas: a. Patients who underwent surgery, chemotherapy, targeted and immunotherapy, iodine in vivo radiation, radiation therapy, or planned to undergo radiation therapy during the trial within 4 weeks of enrollment or 5 half-lives, whichever is shorter; b. Patients who had received intracranial lesion puncture biopsy within 7 days prior to enrollment; c. Received other investigational drugs or treatments that are not on the market within 4 weeks prior to enrollment; d. There was a history of central nervous system bleeding/infarction not associated with antineoplastic agents, such as stroke or intracranial and ocular bleeding (including embolic stroke), during the 6 months prior to enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Brain gliomas",
                    "criterion": "brain gliomas",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who underwent surgery, chemotherapy, targeted and immunotherapy, iodine in vivo radiation, radiation therapy, or planned to undergo radiation therapy during the trial within 4 weeks of enrollment or 5 half-lives, whichever is shorter",
                    "criterion": "recent treatment",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "half-lives"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who had received intracranial lesion puncture biopsy within 7 days prior to enrollment",
                    "criterion": "intracranial lesion puncture biopsy",
                    "requirements": [
                        {
                            "requirement_type": "time since procedure",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 7,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Received other investigational drugs or treatments that are not on the market within 4 weeks prior to enrollment",
                    "criterion": "investigational drugs or treatments",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "There was a history of central nervous system bleeding/infarction not associated with antineoplastic agents, such as stroke or intracranial and ocular bleeding (including embolic stroke), during the 6 months prior to enrollment",
                    "criterion": "central nervous system bleeding/infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 6,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [
        {
            "line": "12. For other solid tumors: a. Received chemotherapy, antibody therapy, molecular-targeted therapy, or investigational drugs within 4 weeks or 5 half-lives (whichever is shorter) of initial administration; b. Patients who underwent major surgery within 28 days prior to administration of the drug or were scheduled to undergo major surgery during the study period (except for procedures such as puncture or lymph node biopsy); c. poorly controlled hypertension (systolic blood pressure &gt; 150 mmHg or diastolic blood pressure &gt; 100 mmHg); d. Previous or associated central nervous system lesions, including but not limited to: paralysis, stroke (except those with lacunar infarction indicated by imaging examination but without treatment), severe brain injury, senile dementia, Parkinson's disease, organic brain syndrome, and psychosis; e. Received other investigational drugs or treatments that were not on the market within 4 weeks prior to enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Received chemotherapy, antibody therapy, molecular-targeted therapy, or investigational drugs within 4 weeks or 5 half-lives (whichever is shorter) of initial administration",
                    "criterion": "recent treatment with chemotherapy, antibody therapy, molecular-targeted therapy, or investigational drugs",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who underwent major surgery within 28 days prior to administration of the drug",
                    "criterion": "recent major surgery",
                    "requirements": [
                        {
                            "requirement_type": "time since surgery",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 28,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "scheduled to undergo major surgery during the study period",
                    "criterion": "scheduled major surgery",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "poorly controlled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg)",
                    "criterion": "poorly controlled hypertension",
                    "requirements": [
                        {
                            "requirement_type": "systolic blood pressure",
                            "expected_value": {
                                "operator": ">",
                                "value": 150,
                                "unit": "mmHg"
                            }
                        },
                        {
                            "requirement_type": "diastolic blood pressure",
                            "expected_value": {
                                "operator": ">",
                                "value": 100,
                                "unit": "mmHg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Previous or associated central nervous system lesions, including but not limited to: paralysis, stroke (except those with lacunar infarction indicated by imaging examination but without treatment), severe brain injury, senile dementia, Parkinson's disease, organic brain syndrome, and psychosis",
                    "criterion": "central nervous system lesions",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Received other investigational drugs or treatments that were not on the market within 4 weeks prior to enrollment",
                    "criterion": "recent treatment with investigational drugs or treatments not on the market",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}