{
    "info": {
        "nct_id": "NCT04759248",
        "official_title": "A Phase II With 2 Parallel Cohorts Clinical Trial Targeting Estrogen Receptor Negative or PAM50 Non-luminal Disease With Atezolizumab in Combination With Trastuzumab and Vinorelbine in HER2-positive Advanced/Metastatic Breast Cancer - ATREZZO Study",
        "inclusion_criteria": "* Male or female (Premenopausal or postmenopausal women)\n* ECOG 0 to 2\n* Histologically confirmed adenocarcinoma of the breast, metastatic or unresectable locally advanced.\n* All patients must have received at least trastuzumab and other anti-HER2 ADCs (including but not limited to T-DM1).\n* Measurable disease according to RECIST 1.1 criteria.\n* Adequate organ function\n* Baseline LVEF ≥50%\n* Participants with asymptomatic brain metastases are eligible.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Treatment with any investigational anticancer drug within 14 days of the start of study treatment.\n* Patient has received Vinorelbine or any other vinca alkaloids previously immediately prior to initiate study treatment.\n* History of other malignant tumors in the past 3 years\n* Known or suspected leptomeningeal disease (LMD)/ poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to brain metastases.\n* Symptomatic hypercalcemia requiring treatment with bisphosphonates in the 14 days prior to inclusion\n* Cardiopulmonary dysfunction\n* Any other severe, uncontrolled\n* Major surgery in the 28 days prior to enrolment\n* Infection with HIV or active Hepatitis B and/or Hepatitis C.\n* History of trastuzumab intolerance, including grade 3-4 infusion reaction or hypersensitivity.\n* Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation\n* History of autoimmune disease,\n* Prior allogeneic stem cell or solid organ transplantation\n* History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan. (Note: History of radiation pneumonitis in the radiation field [fibrosis] is permitted.)\n* Active tuberculosis\n* Receipt of a live, attenuated vaccine within 4 weeks prior to enrollment\n* Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or immune checkpoint targeting agents\n* Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug prior to enrolment\n* Treatment with systemic immunosuppressive medications within 2 weeks prior to enrolment, or anticipated requirement for systemic immunosuppressive medications during the trial.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Male or female (Premenopausal or postmenopausal women)",
            "criterions": [
                {
                    "exact_snippets": "Male or female",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "male",
                                "female"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Premenopausal or postmenopausal women",
                    "criterion": "menopausal status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "premenopausal",
                                "postmenopausal"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ECOG 0 to 2",
            "criterions": [
                {
                    "exact_snippets": "ECOG 0 to 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": "* Histologically confirmed adenocarcinoma of the breast, metastatic or unresectable locally advanced.",
            "criterions": [
                {
                    "exact_snippets": "Histologically confirmed adenocarcinoma of the breast",
                    "criterion": "adenocarcinoma of the breast",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "histologically confirmed"
                        }
                    ]
                },
                {
                    "exact_snippets": "metastatic",
                    "criterion": "metastatic",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unresectable locally advanced",
                    "criterion": "unresectable locally advanced",
                    "requirements": [
                        {
                            "requirement_type": "resectability",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "stage",
                            "expected_value": "locally advanced"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* All patients must have received at least trastuzumab and other anti-HER2 ADCs (including but not limited to T-DM1).",
            "criterions": [
                {
                    "exact_snippets": "received at least trastuzumab",
                    "criterion": "trastuzumab treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "received at least ... other anti-HER2 ADCs",
                    "criterion": "anti-HER2 ADCs treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Measurable disease according to RECIST 1.1 criteria.",
            "criterions": [
                {
                    "exact_snippets": "Measurable disease according to RECIST 1.1 criteria",
                    "criterion": "disease measurability",
                    "requirements": [
                        {
                            "requirement_type": "criteria",
                            "expected_value": "RECIST 1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate organ function",
            "criterions": [
                {
                    "exact_snippets": "Adequate organ function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Baseline LVEF ≥50%",
            "criterions": [
                {
                    "exact_snippets": "Baseline LVEF ≥50%",
                    "criterion": "LVEF",
                    "requirements": [
                        {
                            "requirement_type": "baseline value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants with asymptomatic brain metastases are eligible.",
            "criterions": [
                {
                    "exact_snippets": "asymptomatic brain metastases",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "symptoms",
                            "expected_value": "asymptomatic"
                        }
                    ]
                }
            ]
        },
        {
            "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": "* Treatment with any investigational anticancer drug within 14 days of the start of study treatment.",
            "criterions": [
                {
                    "exact_snippets": "Treatment with any investigational anticancer drug within 14 days of the start of study treatment.",
                    "criterion": "treatment with investigational anticancer drug",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient has received Vinorelbine or any other vinca alkaloids previously immediately prior to initiate study treatment.",
            "criterions": [
                {
                    "exact_snippets": "Patient has received Vinorelbine",
                    "criterion": "Vinorelbine treatment",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "any other vinca alkaloids previously",
                    "criterion": "vinca alkaloids treatment",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of other malignant tumors in the past 3 years",
            "criterions": [
                {
                    "exact_snippets": "History of other malignant tumors in the past 3 years",
                    "criterion": "history of malignant tumors",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known or suspected leptomeningeal disease (LMD)/ poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to brain metastases.",
            "criterions": [
                {
                    "exact_snippets": "Known or suspected leptomeningeal disease (LMD)",
                    "criterion": "leptomeningeal disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "poorly controlled (> 1/week) generalized or complex partial seizures",
                    "criterion": "seizure control",
                    "requirements": [
                        {
                            "requirement_type": "frequency",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "week"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "manifest neurologic progression due to brain metastases",
                    "criterion": "neurologic progression due to brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Symptomatic hypercalcemia requiring treatment with bisphosphonates in the 14 days prior to inclusion",
            "criterions": [
                {
                    "exact_snippets": "Symptomatic hypercalcemia",
                    "criterion": "hypercalcemia",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "requiring treatment with bisphosphonates",
                    "criterion": "treatment with bisphosphonates",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "in the 14 days prior to inclusion",
                    "criterion": "time since treatment with bisphosphonates",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Cardiopulmonary dysfunction",
            "criterions": [
                {
                    "exact_snippets": "Cardiopulmonary dysfunction",
                    "criterion": "cardiopulmonary function",
                    "requirements": [
                        {
                            "requirement_type": "dysfunction",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any other severe, uncontrolled",
            "criterions": [
                {
                    "exact_snippets": "severe, uncontrolled",
                    "criterion": "condition severity",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Major surgery in the 28 days prior to enrolment",
            "criterions": [
                {
                    "exact_snippets": "Major surgery in the 28 days prior to enrolment",
                    "criterion": "major surgery",
                    "requirements": [
                        {
                            "requirement_type": "time since surgery",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Infection with HIV or active Hepatitis B and/or Hepatitis C.",
            "criterions": [
                {
                    "exact_snippets": "Infection with HIV",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active Hepatitis B",
                    "criterion": "active Hepatitis B",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active ... Hepatitis C",
                    "criterion": "active Hepatitis C",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of trastuzumab intolerance, including grade 3-4 infusion reaction or hypersensitivity.",
            "criterions": [
                {
                    "exact_snippets": "History of trastuzumab intolerance",
                    "criterion": "trastuzumab intolerance",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "grade 3-4 infusion reaction",
                    "criterion": "infusion reaction",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "=",
                                "value": 3,
                                "unit": "grade"
                            }
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "=",
                                "value": 4,
                                "unit": "grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity",
                    "criterion": "hypersensitivity",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation",
            "criterions": [
                {
                    "exact_snippets": "Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells",
                    "criterion": "hypersensitivity or allergy to biopharmaceuticals",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Known hypersensitivity or allergy to ... any component of the atezolizumab formulation",
                    "criterion": "hypersensitivity or allergy to atezolizumab components",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of autoimmune disease,",
            "criterions": [
                {
                    "exact_snippets": "History of autoimmune disease",
                    "criterion": "autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior allogeneic stem cell or solid organ transplantation",
            "criterions": [
                {
                    "exact_snippets": "Prior allogeneic stem cell ... transplantation",
                    "criterion": "allogeneic stem cell transplantation",
                    "requirements": [
                        {
                            "requirement_type": "prior occurrence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior ... solid organ transplantation",
                    "criterion": "solid organ transplantation",
                    "requirements": [
                        {
                            "requirement_type": "prior occurrence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan. (Note: History of radiation pneumonitis in the radiation field [fibrosis] is permitted.)",
            "criterions": [
                {
                    "exact_snippets": "History of idiopathic pulmonary fibrosis",
                    "criterion": "idiopathic pulmonary fibrosis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "drug-induced pneumonitis",
                    "criterion": "drug-induced pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia)",
                    "criterion": "organizing pneumonia",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "evidence of active pneumonitis on screening chest CT scan",
                    "criterion": "active pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active tuberculosis",
            "criterions": [
                {
                    "exact_snippets": "Active tuberculosis",
                    "criterion": "tuberculosis",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Receipt of a live, attenuated vaccine within 4 weeks prior to enrollment",
            "criterions": [
                {
                    "exact_snippets": "Receipt of a live, attenuated vaccine within 4 weeks prior to enrollment",
                    "criterion": "live, attenuated vaccine",
                    "requirements": [
                        {
                            "requirement_type": "receipt",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or immune checkpoint targeting agents",
            "criterions": [
                {
                    "exact_snippets": "Prior treatment with CD137 agonists",
                    "criterion": "CD137 agonists treatment",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with ... anti-PD-1",
                    "criterion": "anti-PD-1 therapeutic antibody treatment",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with ... anti-PD-L1 therapeutic antibody",
                    "criterion": "anti-PD-L1 therapeutic antibody treatment",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with ... immune checkpoint targeting agents",
                    "criterion": "immune checkpoint targeting agents treatment",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug prior to enrolment",
            "criterions": [
                {
                    "exact_snippets": "Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug prior to enrolment",
                    "criterion": "treatment with systemic immunostimulatory agents",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Treatment with systemic immunosuppressive medications within 2 weeks prior to enrolment, or anticipated requirement for systemic immunosuppressive medications during the trial.",
            "criterions": [
                {
                    "exact_snippets": "Treatment with systemic immunosuppressive medications within 2 weeks prior to enrolment",
                    "criterion": "systemic immunosuppressive medications",
                    "requirements": [
                        {
                            "requirement_type": "treatment timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks prior to enrolment"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "anticipated requirement for systemic immunosuppressive medications during the trial",
                    "criterion": "systemic immunosuppressive medications",
                    "requirements": [
                        {
                            "requirement_type": "anticipated requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}