{
    "info": {
        "nct_id": "NCT06507891",
        "official_title": "A Phase Ib, Open-label, Dose Escalation and Expansion Study to Evaluate the Tolerance , Pharmacokinetics and Effectiveness of TQ-A3334 Tablets in Patients With Advanced Non-small Cell Lung Cancer",
        "inclusion_criteria": "* Understood and signed an informed consent form;\n* 18 years old and older; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1; life expectancy ≥12 weeks;\n* Histologically confirmed advanced non-small cell lung cancer;\n* Has received at least two systemic chemotherapy regimens which is failure or intolerance；\n* At least one measurable lesion（ based on Response evaluation criteria in solid tumors (RECIST) 1.1;\n* The main organs function are normally；\n* Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study (such as intrauterine devices , contraceptives or condoms) ；No pregnant or breastfeeding women, and a negative pregnancy test are received within 7 days before the randomization；\n* In addition to the above criteria, the extended research phase must meet the following criteria: epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are negative; or patients with positive test results of EGFR and ALK are resistant or intolerant after receiving the targeted drug treatment.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Small cell lung cancer\n* Other malignant tumors that have appeared or are presently present within 5 years, except for cured cervical carcinoma in situ and non-melanoma skin cancer\n* Has received chemotherapy, surgery, radiotherapy, the last treatment from the first dose less than 4 weeks, or oral targeted drugs for less than 5 half-lives, or oral fluorouracil pyridine drugs for less than 14 days, mitomycin C and nitrosourea for less than 6 weeks\n* Expect to use any active vaccine against infectious diseases within 28 days before the first administration or during the study period\n* Immunosuppressive therapy with immunosuppressive agents or systemic or absorbable local hormones (dosage > 10 mg/day prednisone or other therapeutic hormones) is required for the purpose of immunosuppression, and is still in use for 2 weeks after the first administration\n* Active autoimmune diseases that require systemic treatment have occurred within 2 years before the first administration\n* Hypersensitivity to TQ-A3334 or its excipient\n* Has uncontrollable symptoms of brain metastases, spinal cord compression, cancerous meningitis\n* Has unrelieved toxicity reactions ≥ grade 1 due to previous treatment\n* Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with blood vessels is unclear\n* Has thyroid dysfunction that requires drug treatment within 6 months before the first administration\n* Has multiple factors affecting oral medication\n* Has any severe acute complications before the first administration\n* Have participated in other clinical trials within 4 weeks before the first administration\n* According to the judgement of the researchers, there are other factors that may lead to the termination of the study\n* In addition to the above criteria, the extended research phase must meet the following criteria:\n\n  1. Pathologically diagnosed as central, hollow lung squamous cell carcinoma, or non-small cell lung cancer with hemoptysis;\n  2. EGFR and ALK are positive untreated with relevant targeted drugs;\n  3. Has received anlotinib hydrochloride capsules.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Understood and signed an informed consent form;",
            "criterions": [
                {
                    "exact_snippets": "Understood and signed an informed consent form",
                    "criterion": "informed consent form",
                    "requirements": [
                        {
                            "requirement_type": "understanding",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "signature",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 18 years old and older; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1; life expectancy ≥12 weeks;",
            "criterions": [
                {
                    "exact_snippets": "18 years old and older",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1",
                    "criterion": "ECOG performance status score",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "life expectancy ≥12 weeks",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Histologically confirmed advanced non-small cell lung cancer;",
            "criterions": [
                {
                    "exact_snippets": "Histologically confirmed advanced non-small cell lung cancer",
                    "criterion": "non-small cell lung cancer",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "histologically"
                        },
                        {
                            "requirement_type": "stage",
                            "expected_value": "advanced"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has received at least two systemic chemotherapy regimens which is failure or intolerance；",
            "criterions": [
                {
                    "exact_snippets": "Has received at least two systemic chemotherapy regimens",
                    "criterion": "systemic chemotherapy regimens",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "regimens"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "which is failure or intolerance",
                    "criterion": "response to chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "response",
                            "expected_value": [
                                "failure",
                                "intolerance"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* At least one measurable lesion（ based on Response evaluation criteria in solid tumors (RECIST) 1.1;",
            "criterions": [
                {
                    "exact_snippets": "At least one measurable lesion",
                    "criterion": "measurable lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* The main organs function are normally；",
            "criterions": [
                {
                    "exact_snippets": "The main organs function are normally",
                    "criterion": "main organs function",
                    "requirements": [
                        {
                            "requirement_type": "functionality",
                            "expected_value": "normal"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study (such as intrauterine devices , contraceptives or condoms) ；No pregnant or breastfeeding women, and a negative pregnancy test are received within 7 days before the randomization；",
            "criterions": [
                {
                    "exact_snippets": "Male or female subjects should agree to use an adequate method of contraception",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "No pregnant or breastfeeding women",
                    "criterion": "pregnancy or breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "a negative pregnancy test are received within 7 days before the randomization",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* In addition to the above criteria, the extended research phase must meet the following criteria: epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are negative; or patients with positive test results of EGFR and ALK are resistant or intolerant after receiving the targeted drug treatment.",
            "criterions": [
                {
                    "exact_snippets": "epidermal growth factor receptor (EGFR) ... are negative",
                    "criterion": "epidermal growth factor receptor (EGFR)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "anaplastic lymphoma kinase (ALK) ... are negative",
                    "criterion": "anaplastic lymphoma kinase (ALK)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with positive test results of EGFR ... are resistant or intolerant after receiving the targeted drug treatment",
                    "criterion": "epidermal growth factor receptor (EGFR)",
                    "requirements": [
                        {
                            "requirement_type": "treatment response",
                            "expected_value": [
                                "resistant",
                                "intolerant"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with positive test results of ... ALK are resistant or intolerant after receiving the targeted drug treatment",
                    "criterion": "anaplastic lymphoma kinase (ALK)",
                    "requirements": [
                        {
                            "requirement_type": "treatment response",
                            "expected_value": [
                                "resistant",
                                "intolerant"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "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": "* Small cell lung cancer",
            "criterions": [
                {
                    "exact_snippets": "Small cell lung cancer",
                    "criterion": "small cell lung cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Other malignant tumors that have appeared or are presently present within 5 years, except for cured cervical carcinoma in situ and non-melanoma skin cancer",
            "criterions": [
                {
                    "exact_snippets": "Other malignant tumors that have appeared or are presently present within 5 years",
                    "criterion": "other malignant tumors",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "cured cervical carcinoma in situ",
                    "criterion": "cervical carcinoma in situ",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "cured"
                        }
                    ]
                },
                {
                    "exact_snippets": "non-melanoma skin cancer",
                    "criterion": "non-melanoma skin cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has received chemotherapy, surgery, radiotherapy, the last treatment from the first dose less than 4 weeks, or oral targeted drugs for less than 5 half-lives, or oral fluorouracil pyridine drugs for less than 14 days, mitomycin C and nitrosourea for less than 6 weeks",
            "criterions": [
                {
                    "exact_snippets": "Has received chemotherapy",
                    "criterion": "chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "receipt",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Has received ... surgery",
                    "criterion": "surgery",
                    "requirements": [
                        {
                            "requirement_type": "receipt",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Has received ... radiotherapy",
                    "criterion": "radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "receipt",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "the last treatment from the first dose less than 4 weeks",
                    "criterion": "time since last treatment",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "oral targeted drugs for less than 5 half-lives",
                    "criterion": "oral targeted drugs",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 5,
                                "unit": "half-lives"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "oral fluorouracil pyridine drugs for less than 14 days",
                    "criterion": "oral fluorouracil pyridine drugs",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "mitomycin C and nitrosourea for less than 6 weeks",
                    "criterion": "mitomycin C and nitrosourea",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Expect to use any active vaccine against infectious diseases within 28 days before the first administration or during the study period",
            "criterions": [
                {
                    "exact_snippets": "use any active vaccine against infectious diseases within 28 days before the first administration",
                    "criterion": "active vaccine use",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 28,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "use any active vaccine against infectious diseases ... during the study period",
                    "criterion": "active vaccine use",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "during the study period"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Immunosuppressive therapy with immunosuppressive agents or systemic or absorbable local hormones (dosage > 10 mg/day prednisone or other therapeutic hormones) is required for the purpose of immunosuppression, and is still in use for 2 weeks after the first administration",
            "criterions": [
                {
                    "exact_snippets": "Immunosuppressive therapy with immunosuppressive agents or systemic or absorbable local hormones",
                    "criterion": "immunosuppressive therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "dosage > 10 mg/day prednisone or other therapeutic hormones",
                    "criterion": "hormone dosage",
                    "requirements": [
                        {
                            "requirement_type": "dosage",
                            "expected_value": {
                                "operator": ">",
                                "value": 10,
                                "unit": "mg/day"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "is still in use for 2 weeks after the first administration",
                    "criterion": "duration of therapy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active autoimmune diseases that require systemic treatment have occurred within 2 years before the first administration",
            "criterions": [
                {
                    "exact_snippets": "Active autoimmune diseases that require systemic treatment",
                    "criterion": "autoimmune diseases",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        },
                        {
                            "requirement_type": "treatment",
                            "expected_value": "systemic"
                        }
                    ]
                },
                {
                    "exact_snippets": "occurred within 2 years before the first administration",
                    "criterion": "time since last occurrence of autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "time since last occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hypersensitivity to TQ-A3334 or its excipient",
            "criterions": [
                {
                    "exact_snippets": "Hypersensitivity to TQ-A3334",
                    "criterion": "hypersensitivity",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Hypersensitivity to ... its excipient",
                    "criterion": "hypersensitivity to excipient",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has uncontrollable symptoms of brain metastases, spinal cord compression, cancerous meningitis",
            "criterions": [
                {
                    "exact_snippets": "uncontrollable symptoms of brain metastases",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "symptom control",
                            "expected_value": "uncontrollable"
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrollable symptoms of ... spinal cord compression",
                    "criterion": "spinal cord compression",
                    "requirements": [
                        {
                            "requirement_type": "symptom control",
                            "expected_value": "uncontrollable"
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrollable symptoms of ... cancerous meningitis",
                    "criterion": "cancerous meningitis",
                    "requirements": [
                        {
                            "requirement_type": "symptom control",
                            "expected_value": "uncontrollable"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has unrelieved toxicity reactions ≥ grade 1 due to previous treatment",
            "criterions": [
                {
                    "exact_snippets": "unrelieved toxicity reactions ≥ grade 1 due to previous treatment",
                    "criterion": "toxicity reactions",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with blood vessels is unclear",
            "criterions": [
                {
                    "exact_snippets": "Imaging (CT or MRI) shows that tumor invades large blood vessels",
                    "criterion": "tumor invasion of large blood vessels",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Imaging (CT or MRI) shows that ... the boundary with blood vessels is unclear",
                    "criterion": "unclear boundary with blood vessels",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has thyroid dysfunction that requires drug treatment within 6 months before the first administration",
            "criterions": [
                {
                    "exact_snippets": "Has thyroid dysfunction that requires drug treatment within 6 months before the first administration",
                    "criterion": "thyroid dysfunction",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 6,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has multiple factors affecting oral medication",
            "criterions": [
                {
                    "exact_snippets": "multiple factors affecting oral medication",
                    "criterion": "factors affecting oral medication",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": "> 1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has any severe acute complications before the first administration",
            "criterions": [
                {
                    "exact_snippets": "Has any severe acute complications",
                    "criterion": "severe acute complications",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have participated in other clinical trials within 4 weeks before the first administration",
            "criterions": [
                {
                    "exact_snippets": "Have participated in other clinical trials within 4 weeks before the first administration",
                    "criterion": "participation in other clinical trials",
                    "requirements": [
                        {
                            "requirement_type": "time since last participation",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* According to the judgement of the researchers, there are other factors that may lead to the termination of the study",
            "criterions": [
                {
                    "exact_snippets": "other factors that may lead to the termination of the study",
                    "criterion": "factors leading to study termination",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Pathologically diagnosed as central, hollow lung squamous cell carcinoma, or non-small cell lung cancer with hemoptysis;",
            "criterions": [
                {
                    "exact_snippets": "Pathologically diagnosed as central, hollow lung squamous cell carcinoma",
                    "criterion": "central, hollow lung squamous cell carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Pathologically diagnosed as ... non-small cell lung cancer with hemoptysis",
                    "criterion": "non-small cell lung cancer with hemoptysis",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. EGFR and ALK are positive untreated with relevant targeted drugs;",
            "criterions": [
                {
                    "exact_snippets": "EGFR ... positive",
                    "criterion": "EGFR",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "ALK are positive",
                    "criterion": "ALK",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "untreated with relevant targeted drugs",
                    "criterion": "treatment with relevant targeted drugs",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "untreated"
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Has received anlotinib hydrochloride capsules.",
            "criterions": [
                {
                    "exact_snippets": "Has received anlotinib hydrochloride capsules",
                    "criterion": "anlotinib hydrochloride capsules",
                    "requirements": [
                        {
                            "requirement_type": "receipt",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [
        {
            "line": "* In addition to the above criteria, the extended research phase must meet the following criteria:",
            "criterions": []
        }
    ],
    "failed_miscellaneous": []
}