{
    "info": {
        "nct_id": "NCT05139082",
        "official_title": "A Phase I/II Phase Evaluating the Effectiveness and Safety of CDK4/6 Inhibitor (TQB3616) Combined With PD-L1 Monoclonal Antibody (TQB2450) in the Treatment of PD-1/PD-L1 Monoclonal Antibody Resistance and Abnormal Cell Cycle Digestive System Tumors.",
        "inclusion_criteria": "1. Voluntary participation and written informed consent;\n2. Age ≥ 18 years old;\n3. No gender limitation;\n4. Digestive system malignant tumor diagnosed by pathology;\n5. Digestive system tumor patients who have failed standard treatment;\n6. Patients with PD-1 monoclonal antibody or PD-L1 monoclonal antibody treatment failure;\n7. Abnormal cell cycle signaling pathways\n8. Patients with unresectable digestive system tumors confirmed by imaging;\n9. There is at least one measurable lesion (according to the RECIST1.1 standard) or an unmeasurable lesion that can be evaluated, and the imaging diagnosis is ≤21 days from the selection time；\n10. The expected survival period is ≥3 months;\n11. General physical status (ECOG) 0-2;\n12. Sufficient bone marrow hematopoietic function (within 7 days);\n13. Heart, lung, kidney, and liver functions are generally normal.\n14. Women of childbearing age should agree to use effective contraceptive measures during the study period and 6 months after the end of the study, and have a negative serum or urine pregnancy test within 7 days before enrollment in the study; men should agree to use effective contraception during the study period and after the end of the study period 6 Effective contraceptive measures must be used within one month.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. People who are currently receiving other effective treatments;\n2. Patients who are using immunosuppressive agents or systemic or absorptive local hormone therapy to achieve immunosuppression within 2 weeks before the first medication;\n3. Patients who have participated in other clinical trials within 4 weeks before enrollment;\n4. Allergic to study drugs; 5 . Those without measurable tumor lesions, such as body cavity effusion or diffuse infiltration of organs;\n\n6. Those with measurable lesions that have received radiotherapy. 7. Patients with other primary malignant tumors other than digestive system tumors at the same time, except for early solid tumors that have been cured for more than 1 year; 8. Clinically significant cardiovascular diseases, such as heart failure (NYHAIII-IV), are not controlled A history of coronary heart disease, cardiomyopathy, arrhythmia, uncontrolled hypertension or myocardial infarction within the past 1 year; 9. Neurological or mental disorders that affect cognitive ability, including central nervous system metastasis; 10. Existed within 14 days before enrollment Active severe clinical infections (>grade 2 NCI-CTCAE version 5.0), including active tuberculosis; 11. Known or self-reported HIV infection or active hepatitis B or C; 12. Uncontrolled Systemic diseases, such as poorly controlled diabetes; 13. A history of interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis, or evidence of interstitial lung disease on baseline chest X-ray/CT; 14. Keratitis , Ulcerative keratitis or severe dry eye; 15. Known hypersensitivity or allergic reaction to any component of the study drug; 16. Pregnancy (determined by serum β-chorionic gonadotropin test) or breast-feeding.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Voluntary participation and written informed consent;",
            "criterions": [
                {
                    "exact_snippets": "Voluntary participation",
                    "criterion": "participation",
                    "requirements": [
                        {
                            "requirement_type": "voluntary",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "written informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "written",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Age ≥ 18 years old;",
            "criterions": [
                {
                    "exact_snippets": "Age ≥ 18 years old",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. No gender limitation;",
            "criterions": [
                {
                    "exact_snippets": "No gender limitation",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "limitation",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Digestive system malignant tumor diagnosed by pathology;",
            "criterions": [
                {
                    "exact_snippets": "Digestive system malignant tumor",
                    "criterion": "digestive system malignant tumor",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis method",
                            "expected_value": "pathology"
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Digestive system tumor patients who have failed standard treatment;",
            "criterions": [
                {
                    "exact_snippets": "Digestive system tumor patients",
                    "criterion": "digestive system tumor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "failed standard treatment",
                    "criterion": "standard treatment",
                    "requirements": [
                        {
                            "requirement_type": "outcome",
                            "expected_value": "failed"
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Patients with PD-1 monoclonal antibody or PD-L1 monoclonal antibody treatment failure;",
            "criterions": [
                {
                    "exact_snippets": "Patients with PD-1 monoclonal antibody ... treatment failure",
                    "criterion": "PD-1 monoclonal antibody treatment",
                    "requirements": [
                        {
                            "requirement_type": "treatment outcome",
                            "expected_value": "failure"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients with ... PD-L1 monoclonal antibody treatment failure",
                    "criterion": "PD-L1 monoclonal antibody treatment",
                    "requirements": [
                        {
                            "requirement_type": "treatment outcome",
                            "expected_value": "failure"
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Abnormal cell cycle signaling pathways",
            "criterions": [
                {
                    "exact_snippets": "Abnormal cell cycle signaling pathways",
                    "criterion": "cell cycle signaling pathways",
                    "requirements": [
                        {
                            "requirement_type": "abnormality",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Patients with unresectable digestive system tumors confirmed by imaging;",
            "criterions": [
                {
                    "exact_snippets": "unresectable digestive system tumors",
                    "criterion": "digestive system tumors",
                    "requirements": [
                        {
                            "requirement_type": "resectability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "confirmed by imaging",
                    "criterion": "digestive system tumors",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "imaging"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. There is at least one measurable lesion (according to the RECIST1.1 standard) or an unmeasurable lesion that can be evaluated, and the imaging diagnosis is ≤21 days from the selection time；",
            "criterions": [
                {
                    "exact_snippets": "at least one measurable lesion (according to the RECIST1.1 standard)",
                    "criterion": "measurable lesion",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "an unmeasurable lesion that can be evaluated",
                    "criterion": "unmeasurable lesion",
                    "requirements": [
                        {
                            "requirement_type": "evaluability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "imaging diagnosis is ≤21 days from the selection time",
                    "criterion": "imaging diagnosis timing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 21,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. The expected survival period is ≥3 months;",
            "criterions": [
                {
                    "exact_snippets": "expected survival period is ≥3 months",
                    "criterion": "expected survival period",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. General physical status (ECOG) 0-2;",
            "criterions": [
                {
                    "exact_snippets": "General physical status (ECOG) 0-2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Sufficient bone marrow hematopoietic function (within 7 days);",
            "criterions": [
                {
                    "exact_snippets": "Sufficient bone marrow hematopoietic function",
                    "criterion": "bone marrow hematopoietic function",
                    "requirements": [
                        {
                            "requirement_type": "sufficiency",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "within 7 days",
                    "criterion": "time frame for assessment",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 7,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Heart, lung, kidney, and liver functions are generally normal.",
            "criterions": [
                {
                    "exact_snippets": "Heart ... functions are generally normal.",
                    "criterion": "heart function",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "generally normal"
                        }
                    ]
                },
                {
                    "exact_snippets": "lung ... functions are generally normal.",
                    "criterion": "lung function",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "generally normal"
                        }
                    ]
                },
                {
                    "exact_snippets": "kidney ... functions are generally normal.",
                    "criterion": "kidney function",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "generally normal"
                        }
                    ]
                },
                {
                    "exact_snippets": "liver functions are generally normal.",
                    "criterion": "liver function",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "generally normal"
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Women of childbearing age should agree to use effective contraceptive measures during the study period and 6 months after the end of the study, and have a negative serum or urine pregnancy test within 7 days before enrollment in the study; men should agree to use effective contraception during the study period and after the end of the study period 6 Effective contraceptive measures must be used within one month.",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing age",
                    "criterion": "gender and reproductive status",
                    "requirements": [
                        {
                            "requirement_type": "gender",
                            "expected_value": "female"
                        },
                        {
                            "requirement_type": "reproductive status",
                            "expected_value": "childbearing age"
                        }
                    ]
                },
                {
                    "exact_snippets": "agree to use effective contraceptive measures during the study period and 6 months after the end of the study",
                    "criterion": "contraceptive use",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "during the study period and 6 months after the end of the study"
                        }
                    ]
                },
                {
                    "exact_snippets": "have a negative serum or urine pregnancy test within 7 days before enrollment in the study",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 7 days before enrollment"
                        }
                    ]
                },
                {
                    "exact_snippets": "men should agree to use effective contraception during the study period and after the end of the study period 6 Effective contraceptive measures must be used within one month",
                    "criterion": "contraceptive use",
                    "requirements": [
                        {
                            "requirement_type": "gender",
                            "expected_value": "male"
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": "during the study period and after the end of the study period 6 Effective contraceptive measures must be used within one month"
                        }
                    ]
                }
            ]
        },
        {
            "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. People who are currently receiving other effective treatments;",
            "criterions": [
                {
                    "exact_snippets": "currently receiving other effective treatments",
                    "criterion": "current treatment",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "effective"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Patients who are using immunosuppressive agents or systemic or absorptive local hormone therapy to achieve immunosuppression within 2 weeks before the first medication;",
            "criterions": [
                {
                    "exact_snippets": "Patients who are using immunosuppressive agents",
                    "criterion": "use of immunosuppressive agents",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "systemic or absorptive local hormone therapy to achieve immunosuppression",
                    "criterion": "use of hormone therapy for immunosuppression",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "within 2 weeks before the first medication",
                    "criterion": "time since last use of immunosuppressive agents or hormone therapy",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients who have participated in other clinical trials within 4 weeks before enrollment;",
            "criterions": [
                {
                    "exact_snippets": "Patients who have participated in other clinical trials within 4 weeks before enrollment",
                    "criterion": "participation in other clinical trials",
                    "requirements": [
                        {
                            "requirement_type": "time since last participation",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Allergic to study drugs; 5 . Those without measurable tumor lesions, such as body cavity effusion or diffuse infiltration of organs;",
            "criterions": [
                {
                    "exact_snippets": "Allergic to study drugs",
                    "criterion": "allergy to study drugs",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "without measurable tumor lesions",
                    "criterion": "measurable tumor lesions",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "body cavity effusion",
                    "criterion": "body cavity effusion",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "diffuse infiltration of organs",
                    "criterion": "diffuse infiltration of organs",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Those with measurable lesions that have received radiotherapy. 7. Patients with other primary malignant tumors other than digestive system tumors at the same time, except for early solid tumors that have been cured for more than 1 year; 8. Clinically significant cardiovascular diseases, such as heart failure (NYHAIII-IV), are not controlled A history of coronary heart disease, cardiomyopathy, arrhythmia, uncontrolled hypertension or myocardial infarction within the past 1 year; 9. Neurological or mental disorders that affect cognitive ability, including central nervous system metastasis; 10. Existed within 14 days before enrollment Active severe clinical infections (>grade 2 NCI-CTCAE version 5.0), including active tuberculosis; 11. Known or self-reported HIV infection or active hepatitis B or C; 12. Uncontrolled Systemic diseases, such as poorly controlled diabetes; 13. A history of interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis, or evidence of interstitial lung disease on baseline chest X-ray/CT; 14. Keratitis , Ulcerative keratitis or severe dry eye; 15. Known hypersensitivity or allergic reaction to any component of the study drug; 16. Pregnancy (determined by serum β-chorionic gonadotropin test) or breast-feeding.",
            "criterions": [
                {
                    "exact_snippets": "measurable lesions",
                    "criterion": "measurable lesions",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "received radiotherapy",
                    "criterion": "radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "other primary malignant tumors other than digestive system tumors",
                    "criterion": "primary malignant tumors",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "non-digestive system"
                        }
                    ]
                },
                {
                    "exact_snippets": "early solid tumors that have been cured for more than 1 year",
                    "criterion": "early solid tumors",
                    "requirements": [
                        {
                            "requirement_type": "cure duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 1,
                                "unit": "year"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Clinically significant cardiovascular diseases",
                    "criterion": "cardiovascular diseases",
                    "requirements": [
                        {
                            "requirement_type": "clinical significance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "heart failure (NYHAIII-IV)",
                    "criterion": "heart failure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "NYHAIII-IV"
                        }
                    ]
                },
                {
                    "exact_snippets": "not controlled A history of coronary heart disease, cardiomyopathy, arrhythmia, uncontrolled hypertension or myocardial infarction within the past 1 year",
                    "criterion": "coronary heart disease",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "coronary heart disease, cardiomyopathy, arrhythmia, uncontrolled hypertension or myocardial infarction within the past 1 year",
                    "criterion": "cardiomyopathy",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "coronary heart disease, cardiomyopathy, arrhythmia, uncontrolled hypertension or myocardial infarction within the past 1 year",
                    "criterion": "arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "coronary heart disease, cardiomyopathy, arrhythmia, uncontrolled hypertension or myocardial infarction within the past 1 year",
                    "criterion": "uncontrolled hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "coronary heart disease, cardiomyopathy, arrhythmia, uncontrolled hypertension or myocardial infarction within the past 1 year",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "year"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Neurological or mental disorders that affect cognitive ability",
                    "criterion": "neurological or mental disorders",
                    "requirements": [
                        {
                            "requirement_type": "impact",
                            "expected_value": "affect cognitive ability"
                        }
                    ]
                },
                {
                    "exact_snippets": "central nervous system metastasis",
                    "criterion": "central nervous system metastasis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Existed within 14 days before enrollment Active severe clinical infections (>grade 2 NCI-CTCAE version 5.0)",
                    "criterion": "active severe clinical infections",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": ">grade 2 NCI-CTCAE version 5.0"
                        }
                    ]
                },
                {
                    "exact_snippets": "active tuberculosis",
                    "criterion": "active tuberculosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Known or self-reported HIV infection",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active hepatitis B or C",
                    "criterion": "active hepatitis B or C",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled Systemic diseases, such as poorly controlled diabetes",
                    "criterion": "systemic diseases",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "history of interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis",
                    "criterion": "interstitial lung disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "evidence of interstitial lung disease on baseline chest X-ray/CT",
                    "criterion": "interstitial lung disease",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Keratitis , Ulcerative keratitis or severe dry eye",
                    "criterion": "keratitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Keratitis , Ulcerative keratitis or severe dry eye",
                    "criterion": "ulcerative keratitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Keratitis , Ulcerative keratitis or severe dry eye",
                    "criterion": "severe dry eye",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                },
                {
                    "exact_snippets": "Known hypersensitivity or allergic reaction to any component of the study drug",
                    "criterion": "hypersensitivity or allergic reaction",
                    "requirements": [
                        {
                            "requirement_type": "known",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Pregnancy (determined by serum β-chorionic gonadotropin test)",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "determination method",
                            "expected_value": "serum β-chorionic gonadotropin test"
                        }
                    ]
                },
                {
                    "exact_snippets": "breast-feeding",
                    "criterion": "breast-feeding",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}