{
    "info": {
        "nct_id": "NCT06590194",
        "official_title": "A Phase I/IIa, Open-label, Dose-escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Preliminary Anti-tumor Activity of PH009-1 in Patients With EGFR Mutation Locally Advanced or Metastatic NSCLC",
        "inclusion_criteria": "1. Age ≥18 years, signed informed consent form before any trial-related processes.\n2. Histological or cytological confirmed diagnosis of unresectable locally advanced or metastatic NSCLC.\n3. Subjects must have NSCLC harboring one or more active EGFR mutations.\n4. patients must have at least one measurable tumor lesion per RECIST v1.1 criteria as per Investigator's assessment.\n5. The Eastern Cancer Cooperative Group (ECOG) performance score of 0 or 1.\n6. Life expectancy ≥12 weeks.\n7. Adequate hematologic and organ function per protocol.\n8. WOCBP must have a negative serum and/or urine pregnancy test result within 7 days prior to the first dose of PH009-1.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Treatment with any of the following:\n\n   Prior treatment with an EGFR-TKI within 8 days prior to the first dose of PH009-1; Prior treatment with immunotherapy or biotherapy within 4 weeks prior to the first dose of PH009-1; Radiotherapy (palliative radiotherapy completed at least 2 weeks prior to the first dose of Ph009-1 can be enrolled) within 4 weeks prior to the first dose of PH009-1; Herbal therapy that has anti-tumor effects within 2 weeks prior to the first dose of PH009-1; Mitomycin and nitrosourea within 6 weeks prior to the first dose of PH009-1; Oral fluorouracil such as tegafur and capecitabine within 2 weeks prior to the first dose of PH009-1; Chemotherapy (except for mitomycin, nitrosourea, and fluorouracil oral drugs), or other anti-tumor drugs for the treatment of NSCLC within 4 weeks prior to the first dose of PH009-1. Marketed and/or experimental drug treatment for EGFR C797S mutations.\n2. Is currently participating and receiving investigational therapy or using an investigational device, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the investigational product, whichever is longer, prior to the first dose of PH009-1.\n3. Is expected to require any other form of anti-tumor therapy while on study.\n4. Unresolved toxicity greater than CTCAE v5.0 Grade 1 from prior anti-tumor therapy prior to the first dose.\n5. Medical history of severe eye disease or skin disease without recovery to CTCAE v5.0 Grade 0 or 1 prior to the first dose.\n6. Any of the following cardiovascular diseases within the last 6 months: include but not limited to QTc interval ≥ 470 msec.\n7. Medical history of ILD.\n8. Subjects with gastrointestinal disorders that may affect oral administration or interfere with the absorption of PH009-1, or severe gastrointestinal disease within 4 weeks prior to the first dose of PH009-1 and did not recover to ≤ CTCAE v5.0 Grade 2.\n9. Major surgery or significant traumatic injury occurring within 4 weeks prior to the first dose of PH009-1 or anticipation of need for a major surgery during the study.\n10. Has any bleeding tendency or coagulopathy within 6 months prior to the first dose of PH009-1.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Age ≥18 years, signed informed consent form before any trial-related processes.",
            "criterions": [
                {
                    "exact_snippets": "Age ≥18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "signed informed consent form",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Histological or cytological confirmed diagnosis of unresectable locally advanced or metastatic NSCLC.",
            "criterions": [
                {
                    "exact_snippets": "Histological or cytological confirmed diagnosis",
                    "criterion": "diagnosis confirmation method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "histological",
                                "cytological"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "unresectable locally advanced or metastatic NSCLC",
                    "criterion": "NSCLC stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "unresectable locally advanced",
                                "metastatic"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Subjects must have NSCLC harboring one or more active EGFR mutations.",
            "criterions": [
                {
                    "exact_snippets": "Subjects must have NSCLC",
                    "criterion": "NSCLC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "harboring one or more active EGFR mutations",
                    "criterion": "EGFR mutations",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. The Eastern Cancer Cooperative Group (ECOG) performance score of 0 or 1.",
            "criterions": [
                {
                    "exact_snippets": "The Eastern Cancer Cooperative Group (ECOG) performance score of 0 or 1.",
                    "criterion": "ECOG performance score",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Life expectancy ≥12 weeks.",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy ≥12 weeks.",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Adequate hematologic and organ function per protocol.",
            "criterions": [
                {
                    "exact_snippets": "Adequate hematologic ... per protocol.",
                    "criterion": "hematologic function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": "per protocol"
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate ... organ function per protocol.",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": "per protocol"
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. WOCBP must have a negative serum and/or urine pregnancy test result within 7 days prior to the first dose of PH009-1.",
            "criterions": [
                {
                    "exact_snippets": "WOCBP must have a negative serum and/or urine pregnancy test result",
                    "criterion": "pregnancy test result",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "within 7 days prior to the first dose of PH009-1",
                    "criterion": "timing of pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 7 days prior to the first dose of PH009-1"
                        }
                    ]
                }
            ]
        },
        {
            "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. Treatment with any of the following:",
            "criterions": [
                {
                    "exact_snippets": "Treatment with any of the following:",
                    "criterion": "treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Prior treatment with an EGFR-TKI within 8 days prior to the first dose of PH009-1; Prior treatment with immunotherapy or biotherapy within 4 weeks prior to the first dose of PH009-1; Radiotherapy (palliative radiotherapy completed at least 2 weeks prior to the first dose of Ph009-1 can be enrolled) within 4 weeks prior to the first dose of PH009-1; Herbal therapy that has anti-tumor effects within 2 weeks prior to the first dose of PH009-1; Mitomycin and nitrosourea within 6 weeks prior to the first dose of PH009-1; Oral fluorouracil such as tegafur and capecitabine within 2 weeks prior to the first dose of PH009-1; Chemotherapy (except for mitomycin, nitrosourea, and fluorouracil oral drugs), or other anti-tumor drugs for the treatment of NSCLC within 4 weeks prior to the first dose of PH009-1. Marketed and/or experimental drug treatment for EGFR C797S mutations.",
            "criterions": [
                {
                    "exact_snippets": "Prior treatment with an EGFR-TKI within 8 days prior to the first dose of PH009-1",
                    "criterion": "prior EGFR-TKI treatment",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 8,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with immunotherapy or biotherapy within 4 weeks prior to the first dose of PH009-1",
                    "criterion": "prior immunotherapy or biotherapy treatment",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Radiotherapy ... within 4 weeks prior to the first dose of PH009-1",
                    "criterion": "prior radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "palliative radiotherapy completed at least 2 weeks prior to the first dose of Ph009-1",
                    "criterion": "palliative radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Herbal therapy that has anti-tumor effects within 2 weeks prior to the first dose of PH009-1",
                    "criterion": "prior herbal therapy with anti-tumor effects",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Mitomycin and nitrosourea within 6 weeks prior to the first dose of PH009-1",
                    "criterion": "prior mitomycin and nitrosourea treatment",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Oral fluorouracil such as tegafur and capecitabine within 2 weeks prior to the first dose of PH009-1",
                    "criterion": "prior oral fluorouracil treatment",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Chemotherapy (except for mitomycin, nitrosourea, and fluorouracil oral drugs), or other anti-tumor drugs for the treatment of NSCLC within 4 weeks prior to the first dose of PH009-1",
                    "criterion": "prior chemotherapy or other anti-tumor drugs for NSCLC",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Marketed and/or experimental drug treatment for EGFR C797S mutations",
                    "criterion": "drug treatment for EGFR C797S mutations",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Is currently participating and receiving investigational therapy or using an investigational device, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the investigational product, whichever is longer, prior to the first dose of PH009-1.",
            "criterions": [
                {
                    "exact_snippets": "Is currently participating and receiving investigational therapy",
                    "criterion": "current participation in investigational therapy",
                    "requirements": [
                        {
                            "requirement_type": "participation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "using an investigational device",
                    "criterion": "current use of investigational device",
                    "requirements": [
                        {
                            "requirement_type": "usage",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "has participated in a study of an investigational agent and received study therapy",
                    "criterion": "past participation in investigational agent study",
                    "requirements": [
                        {
                            "requirement_type": "participation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "used an investigational device within 4 weeks of the investigational product",
                    "criterion": "past use of investigational device",
                    "requirements": [
                        {
                            "requirement_type": "usage",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Is expected to require any other form of anti-tumor therapy while on study.",
            "criterions": [
                {
                    "exact_snippets": "require any other form of anti-tumor therapy",
                    "criterion": "requirement for anti-tumor therapy",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Unresolved toxicity greater than CTCAE v5.0 Grade 1 from prior anti-tumor therapy prior to the first dose.",
            "criterions": [
                {
                    "exact_snippets": "Unresolved toxicity greater than CTCAE v5.0 Grade 1 from prior anti-tumor therapy",
                    "criterion": "toxicity from prior anti-tumor therapy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 1,
                                "unit": "CTCAE v5.0 Grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Medical history of severe eye disease or skin disease without recovery to CTCAE v5.0 Grade 0 or 1 prior to the first dose.",
            "criterions": [
                {
                    "exact_snippets": "Medical history of severe eye disease",
                    "criterion": "severe eye disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "recovery",
                            "expected_value": "CTCAE v5.0 Grade 0 or 1"
                        }
                    ]
                },
                {
                    "exact_snippets": "Medical history of severe ... skin disease",
                    "criterion": "severe skin disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "recovery",
                            "expected_value": "CTCAE v5.0 Grade 0 or 1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Any of the following cardiovascular diseases within the last 6 months: include but not limited to QTc interval ≥ 470 msec.",
            "criterions": [
                {
                    "exact_snippets": "cardiovascular diseases within the last 6 months",
                    "criterion": "cardiovascular diseases",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within the last 6 months"
                        }
                    ]
                },
                {
                    "exact_snippets": "QTc interval ≥ 470 msec",
                    "criterion": "QTc interval",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 470,
                                "unit": "msec"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Medical history of ILD.",
            "criterions": [
                {
                    "exact_snippets": "Medical history of ILD",
                    "criterion": "interstitial lung disease (ILD)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Subjects with gastrointestinal disorders that may affect oral administration or interfere with the absorption of PH009-1, or severe gastrointestinal disease within 4 weeks prior to the first dose of PH009-1 and did not recover to ≤ CTCAE v5.0 Grade 2.",
            "criterions": [
                {
                    "exact_snippets": "gastrointestinal disorders that may affect oral administration",
                    "criterion": "gastrointestinal disorders",
                    "requirements": [
                        {
                            "requirement_type": "impact on oral administration",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "gastrointestinal disorders that may ... interfere with the absorption of PH009-1",
                    "criterion": "gastrointestinal disorders",
                    "requirements": [
                        {
                            "requirement_type": "interference with absorption",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "severe gastrointestinal disease within 4 weeks prior to the first dose of PH009-1",
                    "criterion": "severe gastrointestinal disease",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": "within 4 weeks prior to the first dose of PH009-1"
                        }
                    ]
                },
                {
                    "exact_snippets": "did not recover to ≤ CTCAE v5.0 Grade 2",
                    "criterion": "recovery from gastrointestinal disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "CTCAE v5.0 Grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Major surgery or significant traumatic injury occurring within 4 weeks prior to the first dose of PH009-1 or anticipation of need for a major surgery during the study.",
            "criterions": [
                {
                    "exact_snippets": "Major surgery or significant traumatic injury occurring within 4 weeks prior to the first dose of PH009-1",
                    "criterion": "major surgery or significant traumatic injury",
                    "requirements": [
                        {
                            "requirement_type": "time since occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "anticipation of need for a major surgery during the study",
                    "criterion": "need for a major surgery",
                    "requirements": [
                        {
                            "requirement_type": "anticipation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Has any bleeding tendency or coagulopathy within 6 months prior to the first dose of PH009-1.",
            "criterions": [
                {
                    "exact_snippets": "Has any bleeding tendency or coagulopathy within 6 months prior to the first dose of PH009-1.",
                    "criterion": "bleeding tendency or coagulopathy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 6 months prior to the first dose of PH009-1"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "4. patients must have at least one measurable tumor lesion per RECIST v1.1 criteria as per Investigator&#39;s assessment.",
            "criterions": [
                {
                    "exact_snippets": "at least one measurable tumor lesion",
                    "criterion": "measurable tumor lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "per RECIST v1.1 criteria",
                    "criterion": "RECIST v1.1 criteria",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "as per Investigator's assessment",
                    "criterion": "Investigator's assessment",
                    "requirements": [
                        {
                            "requirement_type": "source",
                            "expected_value": "Investigator"
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}