{
    "info": {
        "nct_id": "NCT04887831",
        "official_title": "A Phase 2, Randomized, Open-Label Study of Trilaciclib Administered With First-Line Platinum-Based Chemotherapy and Avelumab Maintenance Therapy in Patients With Untreated, Locally Advanced or Metastatic Urothelial Carcinoma (PRESERVE 3)",
        "inclusion_criteria": "1. Age ≥18 years\n2. Histologically documented, locally advanced (T4b, any N; or any T, N 2-3) or metastatic urothelial carcinoma (M1, Stage IV)\n3. Measurable disease as defined by RECIST v1.1\n4. No prior systemic therapy in the inoperable, locally advanced, or metastatic setting including chemotherapy, immune checkpoint inhibitor therapy, targeted therapy, or investigational agents\n5. Archival tumor tissue must be available or a fresh biopsy must be obtained, unless approved by the Medical Monitor\n6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2\n7. Adequate organ function as demonstrated by normal laboratory values\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Prior treatment with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or CD137 agonists, or cytotoxic T-lymphocyte associated protein 4 (CTLA-4) antibody (including ipilimumab), or any other therapeutic antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways in any setting\n2. Malignancies other than urothelial carcinoma within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason ≤6) prostate cancer on surveillance without any plans for treatment intervention (e.g., surgery, radiation, or castration)\n3. Presence of central nervous system (CNS) metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.\n4. QTcF interval > 480 msec. For patients with ventricular pacemakers, QTcF > 500 msec\n5. Known hypersensitivity or allergy to avelumab, gemcitabine, cisplatin or carboplatin\n6. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis, or uncontrolled asthma\n7. Prior hematopoietic stem cell or bone marrow transplantation, or solid organ transplantation\n8. Pregnant or lactating women\n9. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent\n10. Current use of immunosuppressive medication, EXCEPT for the following:\n\n    1. Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)\n    2. Systemic corticosteroids at physiological doses ≤10 mg/day of prednisone or equivalent\n    3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Age ≥18 years",
            "criterions": [
                {
                    "exact_snippets": "Age ≥18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Histologically documented, locally advanced (T4b, any N; or any T, N 2-3) or metastatic urothelial carcinoma (M1, Stage IV)",
            "criterions": [
                {
                    "exact_snippets": "Histologically documented",
                    "criterion": "histological documentation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "locally advanced (T4b, any N; or any T, N 2-3)",
                    "criterion": "locally advanced urothelial carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "T4b, any N",
                                "any T, N 2-3"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "metastatic urothelial carcinoma (M1, Stage IV)",
                    "criterion": "metastatic urothelial carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "M1, Stage IV"
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Measurable disease as defined by RECIST v1.1",
            "criterions": [
                {
                    "exact_snippets": "Measurable disease as defined by RECIST v1.1",
                    "criterion": "measurable disease",
                    "requirements": [
                        {
                            "requirement_type": "definition",
                            "expected_value": "RECIST v1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. No prior systemic therapy in the inoperable, locally advanced, or metastatic setting including chemotherapy, immune checkpoint inhibitor therapy, targeted therapy, or investigational agents",
            "criterions": [
                {
                    "exact_snippets": "No prior systemic therapy in the inoperable, locally advanced, or metastatic setting including chemotherapy",
                    "criterion": "prior systemic therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "immune checkpoint inhibitor therapy",
                    "criterion": "prior immune checkpoint inhibitor therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "targeted therapy",
                    "criterion": "prior targeted therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "investigational agents",
                    "criterion": "prior investigational agents",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Archival tumor tissue must be available or a fresh biopsy must be obtained, unless approved by the Medical Monitor",
            "criterions": [
                {
                    "exact_snippets": "Archival tumor tissue must be available",
                    "criterion": "archival tumor tissue",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "a fresh biopsy must be obtained",
                    "criterion": "fresh biopsy",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status of 0-2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Adequate organ function as demonstrated by normal laboratory values",
            "criterions": [
                {
                    "exact_snippets": "Adequate organ function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": "adequate"
                        }
                    ]
                },
                {
                    "exact_snippets": "normal laboratory values",
                    "criterion": "laboratory values",
                    "requirements": [
                        {
                            "requirement_type": "normality",
                            "expected_value": "normal"
                        }
                    ]
                }
            ]
        },
        {
            "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. Prior treatment with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or CD137 agonists, or cytotoxic T-lymphocyte associated protein 4 (CTLA-4) antibody (including ipilimumab), or any other therapeutic antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways in any setting",
            "criterions": [
                {
                    "exact_snippets": "Prior treatment with IL-2",
                    "criterion": "prior treatment with IL-2",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with ... IFN-α",
                    "criterion": "prior treatment with IFN-α",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with ... anti-PD-1",
                    "criterion": "prior treatment with anti-PD-1",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with ... anti-PD-L1",
                    "criterion": "prior treatment with anti-PD-L1",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with ... anti-PD-L2",
                    "criterion": "prior treatment with anti-PD-L2",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with ... anti-CD137",
                    "criterion": "prior treatment with anti-CD137",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with ... CD137 agonists",
                    "criterion": "prior treatment with CD137 agonists",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with ... cytotoxic T-lymphocyte associated protein 4 (CTLA-4) antibody (including ipilimumab)",
                    "criterion": "prior treatment with CTLA-4 antibody",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with ... any other therapeutic antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways",
                    "criterion": "prior treatment with therapeutic antibody or drug targeting T cell co-stimulation or immune checkpoint pathways",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Malignancies other than urothelial carcinoma within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason ≤6) prostate cancer on surveillance without any plans for treatment intervention (e.g., surgery, radiation, or castration)",
            "criterions": [
                {
                    "exact_snippets": "Malignancies other than urothelial carcinoma within 3 years prior to randomization",
                    "criterion": "other malignancies",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "adequately treated basal cell or squamous cell skin cancer",
                    "criterion": "basal cell or squamous cell skin cancer",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "adequately treated"
                        }
                    ]
                },
                {
                    "exact_snippets": "carcinoma in situ of the breast or of the cervix",
                    "criterion": "carcinoma in situ",
                    "requirements": [
                        {
                            "requirement_type": "location",
                            "expected_value": [
                                "breast",
                                "cervix"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "low-grade (Gleason ≤6) prostate cancer on surveillance without any plans for treatment intervention",
                    "criterion": "low-grade prostate cancer",
                    "requirements": [
                        {
                            "requirement_type": "Gleason score",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "Gleason"
                            }
                        },
                        {
                            "requirement_type": "treatment plans",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Presence of central nervous system (CNS) metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.",
            "criterions": [
                {
                    "exact_snippets": "Presence of central nervous system (CNS) metastases",
                    "criterion": "central nervous system (CNS) metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Presence of ... leptomeningeal disease",
                    "criterion": "leptomeningeal disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "requiring immediate treatment with radiation therapy",
                    "criterion": "immediate treatment with radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "requiring immediate treatment with ... steroids",
                    "criterion": "immediate treatment with steroids",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. QTcF interval > 480 msec. For patients with ventricular pacemakers, QTcF > 500 msec",
            "criterions": [
                {
                    "exact_snippets": "QTcF interval > 480 msec",
                    "criterion": "QTcF interval",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 480,
                                "unit": "msec"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ventricular pacemakers ... QTcF > 500 msec",
                    "criterion": "QTcF interval for patients with ventricular pacemakers",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 500,
                                "unit": "msec"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Known hypersensitivity or allergy to avelumab, gemcitabine, cisplatin or carboplatin",
            "criterions": [
                {
                    "exact_snippets": "hypersensitivity or allergy to avelumab",
                    "criterion": "hypersensitivity or allergy",
                    "requirements": [
                        {
                            "requirement_type": "substance",
                            "expected_value": "avelumab"
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity or allergy to ... gemcitabine",
                    "criterion": "hypersensitivity or allergy",
                    "requirements": [
                        {
                            "requirement_type": "substance",
                            "expected_value": "gemcitabine"
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity or allergy to ... cisplatin",
                    "criterion": "hypersensitivity or allergy",
                    "requirements": [
                        {
                            "requirement_type": "substance",
                            "expected_value": "cisplatin"
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity or allergy to ... carboplatin",
                    "criterion": "hypersensitivity or allergy",
                    "requirements": [
                        {
                            "requirement_type": "substance",
                            "expected_value": "carboplatin"
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis, or uncontrolled asthma",
            "criterions": [
                {
                    "exact_snippets": "Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3)",
                    "criterion": "hypersensitivity reactions to monoclonal antibodies",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "any history of anaphylaxis",
                    "criterion": "history of anaphylaxis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled asthma",
                    "criterion": "asthma",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Prior hematopoietic stem cell or bone marrow transplantation, or solid organ transplantation",
            "criterions": [
                {
                    "exact_snippets": "Prior hematopoietic stem cell or bone marrow transplantation",
                    "criterion": "hematopoietic stem cell or bone marrow transplantation",
                    "requirements": [
                        {
                            "requirement_type": "prior occurrence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "solid organ transplantation",
                    "criterion": "solid organ transplantation",
                    "requirements": [
                        {
                            "requirement_type": "prior occurrence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Pregnant or lactating women",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "lactating women",
                    "criterion": "lactation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent",
            "criterions": [
                {
                    "exact_snippets": "Active autoimmune disease",
                    "criterion": "autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "might deteriorate when receiving an immunostimulatory agent",
                    "criterion": "deterioration risk with immunostimulatory agent",
                    "requirements": [
                        {
                            "requirement_type": "risk",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Current use of immunosuppressive medication, EXCEPT for the following:",
            "criterions": [
                {
                    "exact_snippets": "Current use of immunosuppressive medication",
                    "criterion": "immunosuppressive medication use",
                    "requirements": [
                        {
                            "requirement_type": "current use",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)",
            "criterions": [
                {
                    "exact_snippets": "Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)",
                    "criterion": "steroid administration route",
                    "requirements": [
                        {
                            "requirement_type": "types",
                            "expected_value": [
                                "intranasal",
                                "inhaled",
                                "topical",
                                "local injection"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Systemic corticosteroids at physiological doses ≤10 mg/day of prednisone or equivalent",
            "criterions": [
                {
                    "exact_snippets": "Systemic corticosteroids ... ≤10 mg/day of prednisone or equivalent",
                    "criterion": "systemic corticosteroids",
                    "requirements": [
                        {
                            "requirement_type": "dose",
                            "expected_value": {
                                "operator": "<=",
                                "value": 10,
                                "unit": "mg/day of prednisone or equivalent"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)",
            "criterions": [
                {
                    "exact_snippets": "Steroids as premedication for hypersensitivity reactions",
                    "criterion": "steroids premedication",
                    "requirements": [
                        {
                            "requirement_type": "purpose",
                            "expected_value": "hypersensitivity reactions"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}