{
    "info": {
        "nct_id": "NCT04235101",
        "official_title": "A Two-part Phase I Study With the Antibody-drug Conjugate SYD985 in Combination With Niraparib to Evaluate Safety, Pharmacokinetics and Efficacy in Patients With HER2-expressing Locally Advanced or Metastatic Solid Tumors.",
        "inclusion_criteria": "* Male or female, age ≥ 18 years at the time of signing first informed consent;\n* Patient with a histologically-confirmed, locally advanced or metastatic tumour who has progressed on standard therapy or for whom no standard therapy exists, with the following restriction:\n\n  * Part 1: solid tumours of any origin;\n  * Part 2: breast cancer, ovarian cancer or endometrial carcinoma/carcinosarcoma;\n* HER2 tumor status at least 1+ as assessed by immunohistochemistry (IHC) as determined by the local laboratory;\n* Presence of a tumor lesion accessible for biopsy and patient should be willing to undergo a fresh biopsy for central HER2 testing and genetic testing, unless adequate (biopsy) tumour material is available obtained < 6 months prior to signing the main informed consent;\n* At least one measurable cancer lesion as defined by the Response Evaluation Criteria for Solid Tumours (RECIST version 1.1);\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;\n* Adequate organ function.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Having been treated with:\n\n  1. DUBA-containing ADCs at any time;\n  2. Anthracycline treatment within 8 weeks prior to start of study treatment;\n  3. Other anticancer therapy including chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to start of study treatment or 5 times the half-life of the therapy, whichever is shorter;\n  4. Radiotherapy within 4 weeks prior to start of study treatment or within 1 week for palliative care (as long as the lungs were not exposed);\n  5. Hormone therapy within 1 week prior to start of study treatment. The patient must have sufficiently recovered from any treatment-related toxicities to NCI CTCAE Grade ≤ 1 (except for toxicities not considered a safety risk for the patient at the investigator's discretion);\n* History or presence of keratitis;\n* Left ventricular ejection fraction (LVEF) < 50% as assessed by either echocardiography or multigated acquisition (MUGA) scan at screening, or a history of clinically significant decrease in LVEF during previous trastuzumab containing treatment leading to permanent discontinuation of treatment;\n* History (within 6 months prior to start of study treatment) or presence of clinically significant cardiovascular disease such as unstable angina, congestive heart failure, myocardial infarction, uncontrolled hypertension, or cardiac arrhythmia requiring medication;\n* History or presence of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan;\n* Severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease) at screening;\n* Symptomatic brain metastases, brain metastasis requiring steroids to manage symptoms or treatment for brain metastases within 8 weeks prior to start of study treatment.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Male or female, age ≥ 18 years at the time of signing first informed consent;",
            "criterions": [
                {
                    "exact_snippets": "Male or female",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "age ≥ 18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient with a histologically-confirmed, locally advanced or metastatic tumour who has progressed on standard therapy or for whom no standard therapy exists, with the following restriction:",
            "criterions": [
                {
                    "exact_snippets": "histologically-confirmed, locally advanced or metastatic tumour",
                    "criterion": "tumour status",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "histologically-confirmed"
                        },
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "locally advanced",
                                "metastatic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "progressed on standard therapy",
                    "criterion": "progression on standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "for whom no standard therapy exists",
                    "criterion": "availability of standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Part 1: solid tumours of any origin;",
            "criterions": [
                {
                    "exact_snippets": "solid tumours of any origin",
                    "criterion": "solid tumours",
                    "requirements": [
                        {
                            "requirement_type": "origin",
                            "expected_value": "any"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Part 2: breast cancer, ovarian cancer or endometrial carcinoma/carcinosarcoma;",
            "criterions": [
                {
                    "exact_snippets": "breast cancer",
                    "criterion": "breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ovarian cancer",
                    "criterion": "ovarian cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "endometrial carcinoma/carcinosarcoma",
                    "criterion": "endometrial carcinoma/carcinosarcoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* HER2 tumor status at least 1+ as assessed by immunohistochemistry (IHC) as determined by the local laboratory;",
            "criterions": [
                {
                    "exact_snippets": "HER2 tumor status at least 1+ ... as assessed by immunohistochemistry (IHC)",
                    "criterion": "HER2 tumor status",
                    "requirements": [
                        {
                            "requirement_type": "assessment method",
                            "expected_value": "immunohistochemistry (IHC)"
                        },
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "+"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Presence of a tumor lesion accessible for biopsy and patient should be willing to undergo a fresh biopsy for central HER2 testing and genetic testing, unless adequate (biopsy) tumour material is available obtained < 6 months prior to signing the main informed consent;",
            "criterions": [
                {
                    "exact_snippets": "Presence of a tumor lesion accessible for biopsy",
                    "criterion": "tumor lesion",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "accessibility for biopsy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patient should be willing to undergo a fresh biopsy",
                    "criterion": "willingness to undergo fresh biopsy",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "adequate (biopsy) tumour material is available obtained < 6 months prior to signing the main informed consent",
                    "criterion": "biopsy tumour material",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "recency",
                            "expected_value": {
                                "operator": "<",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* At least one measurable cancer lesion as defined by the Response Evaluation Criteria for Solid Tumours (RECIST version 1.1);",
            "criterions": [
                {
                    "exact_snippets": "At least one measurable cancer lesion",
                    "criterion": "measurable cancer lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "performance status",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate organ function.",
            "criterions": [
                {
                    "exact_snippets": "Adequate organ function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "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": "* Having been treated with:",
            "criterions": [
                {
                    "exact_snippets": "Having been treated with",
                    "criterion": "prior treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. DUBA-containing ADCs at any time;",
            "criterions": [
                {
                    "exact_snippets": "DUBA-containing ADCs at any time",
                    "criterion": "DUBA-containing ADCs",
                    "requirements": [
                        {
                            "requirement_type": "exposure",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Anthracycline treatment within 8 weeks prior to start of study treatment;",
            "criterions": [
                {
                    "exact_snippets": "Anthracycline treatment within 8 weeks prior to start of study treatment",
                    "criterion": "anthracycline treatment",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 8,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Other anticancer therapy including chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to start of study treatment or 5 times the half-life of the therapy, whichever is shorter;",
            "criterions": [
                {
                    "exact_snippets": "Other anticancer therapy including chemotherapy, immunotherapy, or investigational agents",
                    "criterion": "anticancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "within 4 weeks prior to start of study treatment or 5 times the half-life of the therapy, whichever is shorter",
                    "criterion": "time since last anticancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "times the half-life of the therapy"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Radiotherapy within 4 weeks prior to start of study treatment or within 1 week for palliative care (as long as the lungs were not exposed);",
            "criterions": [
                {
                    "exact_snippets": "Radiotherapy within 4 weeks prior to start of study treatment",
                    "criterion": "radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Radiotherapy ... within 1 week for palliative care (as long as the lungs were not exposed)",
                    "criterion": "radiotherapy for palliative care",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "week"
                            }
                        },
                        {
                            "requirement_type": "lung exposure",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Hormone therapy within 1 week prior to start of study treatment. The patient must have sufficiently recovered from any treatment-related toxicities to NCI CTCAE Grade ≤ 1 (except for toxicities not considered a safety risk for the patient at the investigator's discretion);",
            "criterions": [
                {
                    "exact_snippets": "Hormone therapy within 1 week prior to start of study treatment",
                    "criterion": "hormone therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "week"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "sufficiently recovered from any treatment-related toxicities to NCI CTCAE Grade ≤ 1",
                    "criterion": "treatment-related toxicities",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "NCI CTCAE Grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History or presence of keratitis;",
            "criterions": [
                {
                    "exact_snippets": "History or presence of keratitis",
                    "criterion": "keratitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Left ventricular ejection fraction (LVEF) < 50% as assessed by either echocardiography or multigated acquisition (MUGA) scan at screening, or a history of clinically significant decrease in LVEF during previous trastuzumab containing treatment leading to permanent discontinuation of treatment;",
            "criterions": [
                {
                    "exact_snippets": "Left ventricular ejection fraction (LVEF) < 50%",
                    "criterion": "left ventricular ejection fraction (LVEF)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "history of clinically significant decrease in LVEF during previous trastuzumab containing treatment leading to permanent discontinuation of treatment",
                    "criterion": "history of clinically significant decrease in LVEF",
                    "requirements": [
                        {
                            "requirement_type": "treatment impact",
                            "expected_value": "permanent discontinuation of trastuzumab containing treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History (within 6 months prior to start of study treatment) or presence of clinically significant cardiovascular disease such as unstable angina, congestive heart failure, myocardial infarction, uncontrolled hypertension, or cardiac arrhythmia requiring medication;",
            "criterions": [
                {
                    "exact_snippets": "History (within 6 months prior to start of study treatment) or presence of clinically significant cardiovascular disease such as unstable angina",
                    "criterion": "unstable angina",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History (within 6 months prior to start of study treatment) or presence of clinically significant cardiovascular disease such as ... congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History (within 6 months prior to start of study treatment) or presence of clinically significant cardiovascular disease such as ... myocardial infarction",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History (within 6 months prior to start of study treatment) or presence of clinically significant cardiovascular disease such as ... uncontrolled hypertension",
                    "criterion": "uncontrolled hypertension",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History (within 6 months prior to start of study treatment) or presence of clinically significant cardiovascular disease such as ... cardiac arrhythmia requiring medication",
                    "criterion": "cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "medication requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History or presence of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan;",
            "criterions": [
                {
                    "exact_snippets": "History or presence of idiopathic pulmonary fibrosis",
                    "criterion": "idiopathic pulmonary fibrosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History or presence of ... organizing pneumonia (e.g. bronchiolitis obliterans)",
                    "criterion": "organizing pneumonia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History or presence of ... drug-induced pneumonitis",
                    "criterion": "drug-induced pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History or presence of ... idiopathic pneumonitis",
                    "criterion": "idiopathic pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "evidence of active pneumonitis on screening chest CT scan",
                    "criterion": "active pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease) at screening;",
            "criterions": [
                {
                    "exact_snippets": "Severe, uncontrolled systemic disease",
                    "criterion": "systemic disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically significant cardiovascular ... disease",
                    "criterion": "cardiovascular disease",
                    "requirements": [
                        {
                            "requirement_type": "clinical significance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically significant ... pulmonary ... disease",
                    "criterion": "pulmonary disease",
                    "requirements": [
                        {
                            "requirement_type": "clinical significance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically significant ... metabolic disease",
                    "criterion": "metabolic disease",
                    "requirements": [
                        {
                            "requirement_type": "clinical significance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Symptomatic brain metastases, brain metastasis requiring steroids to manage symptoms or treatment for brain metastases within 8 weeks prior to start of study treatment.",
            "criterions": [
                {
                    "exact_snippets": "Symptomatic brain metastases",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "brain metastasis requiring steroids to manage symptoms",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "steroid requirement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment for brain metastases within 8 weeks prior to start of study treatment",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "treatment timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 8,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}