{
    "info": {
        "nct_id": "NCT06188520",
        "official_title": "A Phase I/IIa, First-in-human, Open-label, Dose Escalation and Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of AZD8421 Alone or in Combination in Participants With Selected Advanced or Metastatic Solid Tumors",
        "inclusion_criteria": "* Female participants only, aged 18 or above\n* Participants with advanced solid tumors must have received prior adequate therapy in accordance with local practice for their tumor type and stage of disease, or, in the opinion of the Investigator, a clinical study is the best option for their next treatment based on response to and/or tolerability of prior therapy.\n* Metastatic or locoregionally recurrent disease and radiological or objective evidence of progression on or after the last systemic therapy prior to starting IMP.\n* ECOG/WHO performance status 0 to 1, and a minimum life expectancy of 12 weeks.\n* At least one lesion that is measurable and/or non-measurable, as per RECIST v1.1 and that can be accurately assessed at baseline and is suitable for repeated assessment.\nHealthy volunteers allowed\nMust be FEMALE\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Intervention with any of the following:\n* Any cytotoxic chemotherapy, investigational agents, or other anti-cancer drugs for the treatment of advanced cancer from a previous treatment regimen or clinical study within 14 days or 5 half-lives (whichever is shorter) of the first dose of IMP (21 days for myelosuppressive therapies) other than GnRHa (eg, goserelin) and bone-stabilizing agents (eg, zoledronic acid, denosumab).\n* Any prescription or non-prescription drugs or other products, including herbal products, known to be moderate or strong inhibitors/inducers of CYP3A4/5 which cannot be discontinued prior to first dose of IMP and withheld throughout the study until 2 weeks after the last dose of study drug.\n* Drugs that have a known risk of Torsades de Pointes.\n* Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of IMP.\n* Major surgical procedure or significant traumatic injury, within 4 weeks of the first dose of IMP, or an anticipated need for major surgery and/or any surgery requiring general anesthesia during the study.\n* Any unresolved toxicities of Grade ≥ 2 from prior anti-cancer therapy (with the exception of alopecia). Participants with stable ≤ Grade 2 neuropathy are eligible.\n* Presence of life-threatening metastatic visceral disease, as judged by the Investigator, uncontrolled CNS metastatic disease. Participants with spinal cord compression and/or brain metastases may be enrolled if definitively treated (eg, surgery or radiotherapy) and stable off steroids for at least 4 weeks prior to start of IMP.\n* Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, or eg, infection requiring IV antibiotic therapy, or active infection including hepatitis B, hepatitis C, and HIV (active viral infection is defined as requiring antiviral therapy; screening for chronic conditions is not required).\n* Any of the following cardiac criteria:\n* Mean resting QTcF > 470 msec obtained from a triplicate ECG\n* Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (eg, complete left bundle branch block, second- and third-degree heart block), or clinically significant sinus pause. Participants with controlled atrial fibrillation can be enrolled.\n* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as symptomatic heart failure, hypokalemia, congenital long QT syndrome, immediate family history of long QT syndrome or unexplained sudden death at < 40 years of age. Hypertrophic cardiomyopathy and clinically significant stenotic valve disease.\n* LVEF < 50%, and/or experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, unstable angina pectoris, congestive heart failure NYHA Grade ≥ 2, cerebrovascular accident, or transient ischemic attack.\n* Uncontrolled hypertension.\n* Inadequate bone marrow reserve or organ function as demonstrated by relevant laboratory values:\n* Refractory nausea and vomiting, uncontrolled chronic gastrointestinal diseases, or previous significant bowel resection that would preclude adequate absorption of IMP(s).\n* History of hypersensitivity to active or inactive excipients of AZD8421 or drugs with a similar chemical structure or class to AZD8421.\n* Previous treatment with AZD8421 or with any CDK2-selective inhibitor, or protein kinase membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase 1 (PKMYT1) inhibitor, or WEE1 inhibitor.\n* Currently pregnant (confirmed with positive pregnancy test), breast feeding, or planning to become pregnant. Participants of childbearing potential must agree to use one highly effective contraceptive measure.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Female participants only, aged 18 or above",
            "criterions": [
                {
                    "exact_snippets": "Female participants only",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": "female"
                        }
                    ]
                },
                {
                    "exact_snippets": "aged 18 or above",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Participants with advanced solid tumors must have received prior adequate therapy in accordance with local practice for their tumor type and stage of disease, or, in the opinion of the Investigator, a clinical study is the best option for their next treatment based on response to and/or tolerability of prior therapy.",
            "criterions": [
                {
                    "exact_snippets": "Participants with advanced solid tumors",
                    "criterion": "advanced solid tumors",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must have received prior adequate therapy",
                    "criterion": "prior adequate therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "in accordance with local practice for their tumor type and stage of disease",
                    "criterion": "local practice for tumor type and stage of disease",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "in the opinion of the Investigator, a clinical study is the best option for their next treatment",
                    "criterion": "Investigator's opinion on clinical study as best option",
                    "requirements": [
                        {
                            "requirement_type": "opinion",
                            "expected_value": "clinical study is best option"
                        }
                    ]
                },
                {
                    "exact_snippets": "based on response to and/or tolerability of prior therapy",
                    "criterion": "response to and/or tolerability of prior therapy",
                    "requirements": [
                        {
                            "requirement_type": "evaluation",
                            "expected_value": "response and/or tolerability"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Metastatic or locoregionally recurrent disease and radiological or objective evidence of progression on or after the last systemic therapy prior to starting IMP.",
            "criterions": [
                {
                    "exact_snippets": "Metastatic or locoregionally recurrent disease",
                    "criterion": "disease status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "metastatic",
                                "locoregionally recurrent"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "radiological or objective evidence of progression",
                    "criterion": "disease progression",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": [
                                "radiological",
                                "objective"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "progression on or after the last systemic therapy",
                    "criterion": "progression timing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "on or after the last systemic therapy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ECOG/WHO performance status 0 to 1, and a minimum life expectancy of 12 weeks.",
            "criterions": [
                {
                    "exact_snippets": "ECOG/WHO performance status 0 to 1",
                    "criterion": "ECOG/WHO performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "minimum life expectancy of 12 weeks",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* At least one lesion that is measurable and/or non-measurable, as per RECIST v1.1 and that can be accurately assessed at baseline and is suitable for repeated assessment.",
            "criterions": [
                {
                    "exact_snippets": "At least one lesion that is measurable and/or non-measurable, as per RECIST v1.1",
                    "criterion": "lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        },
                        {
                            "requirement_type": "measurability",
                            "expected_value": [
                                "measurable",
                                "non-measurable"
                            ]
                        },
                        {
                            "requirement_type": "standard",
                            "expected_value": "RECIST v1.1"
                        }
                    ]
                },
                {
                    "exact_snippets": "lesion ... can be accurately assessed at baseline",
                    "criterion": "lesion assessment at baseline",
                    "requirements": [
                        {
                            "requirement_type": "accuracy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "lesion ... suitable for repeated assessment",
                    "criterion": "lesion suitability for repeated assessment",
                    "requirements": [
                        {
                            "requirement_type": "suitability",
                            "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 be FEMALE",
            "criterions": [
                {
                    "exact_snippets": "Must be FEMALE",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "female"
                        }
                    ]
                }
            ]
        },
        {
            "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": "* Intervention with any of the following:",
            "criterions": [
                {
                    "exact_snippets": "Intervention with any of the following",
                    "criterion": "intervention",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any cytotoxic chemotherapy, investigational agents, or other anti-cancer drugs for the treatment of advanced cancer from a previous treatment regimen or clinical study within 14 days or 5 half-lives (whichever is shorter) of the first dose of IMP (21 days for myelosuppressive therapies) other than GnRHa (eg, goserelin) and bone-stabilizing agents (eg, zoledronic acid, denosumab).",
            "criterions": [
                {
                    "exact_snippets": "Any cytotoxic chemotherapy ... within 14 days or 5 half-lives (whichever is shorter) of the first dose of IMP",
                    "criterion": "cytotoxic chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 14,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Any ... investigational agents ... within 14 days or 5 half-lives (whichever is shorter) of the first dose of IMP",
                    "criterion": "investigational agents",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 14,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Any ... other anti-cancer drugs for the treatment of advanced cancer ... within 14 days or 5 half-lives (whichever is shorter) of the first dose of IMP",
                    "criterion": "other anti-cancer drugs for the treatment of advanced cancer",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 14,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "myelosuppressive therapies ... within ... 21 days ... of the first dose of IMP",
                    "criterion": "myelosuppressive therapies",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 21,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any prescription or non-prescription drugs or other products, including herbal products, known to be moderate or strong inhibitors/inducers of CYP3A4/5 which cannot be discontinued prior to first dose of IMP and withheld throughout the study until 2 weeks after the last dose of study drug.",
            "criterions": [
                {
                    "exact_snippets": "Any prescription or non-prescription drugs or other products, including herbal products, known to be moderate or strong inhibitors/inducers of CYP3A4/5",
                    "criterion": "use of CYP3A4/5 inhibitors/inducers",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Drugs that have a known risk of Torsades de Pointes.",
            "criterions": [
                {
                    "exact_snippets": "Drugs that have a known risk of Torsades de Pointes",
                    "criterion": "drugs",
                    "requirements": [
                        {
                            "requirement_type": "risk",
                            "expected_value": "Torsades de Pointes"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of IMP.",
            "criterions": [
                {
                    "exact_snippets": "Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of IMP.",
                    "criterion": "radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "field size",
                            "expected_value": "limited"
                        },
                        {
                            "requirement_type": "purpose",
                            "expected_value": "palliation"
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 1 week of the first dose of IMP"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Major surgical procedure or significant traumatic injury, within 4 weeks of the first dose of IMP, or an anticipated need for major surgery and/or any surgery requiring general anesthesia during the study.",
            "criterions": [
                {
                    "exact_snippets": "Major surgical procedure or significant traumatic injury, within 4 weeks of the first dose of IMP",
                    "criterion": "recent major surgery or significant traumatic injury",
                    "requirements": [
                        {
                            "requirement_type": "time since occurrence",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "anticipated need for major surgery",
                    "criterion": "anticipated need for major surgery",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "any surgery requiring general anesthesia during the study",
                    "criterion": "surgery requiring general anesthesia during the study",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any unresolved toxicities of Grade ≥ 2 from prior anti-cancer therapy (with the exception of alopecia). Participants with stable ≤ Grade 2 neuropathy are eligible.",
            "criterions": [
                {
                    "exact_snippets": "unresolved toxicities of Grade ≥ 2 from prior anti-cancer therapy",
                    "criterion": "unresolved toxicities from prior anti-cancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alopecia",
                    "criterion": "alopecia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "stable ≤ Grade 2 neuropathy",
                    "criterion": "neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": "stable"
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "Grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Presence of life-threatening metastatic visceral disease, as judged by the Investigator, uncontrolled CNS metastatic disease. Participants with spinal cord compression and/or brain metastases may be enrolled if definitively treated (eg, surgery or radiotherapy) and stable off steroids for at least 4 weeks prior to start of IMP.",
            "criterions": [
                {
                    "exact_snippets": "Presence of life-threatening metastatic visceral disease",
                    "criterion": "life-threatening metastatic visceral disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled CNS metastatic disease",
                    "criterion": "uncontrolled CNS metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants with spinal cord compression and/or brain metastases may be enrolled if definitively treated (eg, surgery or radiotherapy)",
                    "criterion": "spinal cord compression and/or brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "definitively treated (eg, surgery or radiotherapy)"
                        }
                    ]
                },
                {
                    "exact_snippets": "stable off steroids for at least 4 weeks prior to start of IMP",
                    "criterion": "stability off steroids",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, or eg, infection requiring IV antibiotic therapy, or active infection including hepatitis B, hepatitis C, and HIV (active viral infection is defined as requiring antiviral therapy; screening for chronic conditions is not required).",
            "criterions": [
                {
                    "exact_snippets": "severe or uncontrolled systemic diseases",
                    "criterion": "systemic diseases",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled hypertension",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "active bleeding diatheses",
                    "criterion": "bleeding diatheses",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "infection requiring IV antibiotic therapy",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "IV antibiotic therapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "active infection including hepatitis B, hepatitis C, and HIV",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "types",
                            "expected_value": [
                                "hepatitis B",
                                "hepatitis C",
                                "HIV"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "active viral infection is defined as requiring antiviral therapy",
                    "criterion": "viral infection",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "treatment",
                            "expected_value": "antiviral therapy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any of the following cardiac criteria:",
            "criterions": [
                {
                    "exact_snippets": "Any of the following cardiac criteria",
                    "criterion": "cardiac criteria",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Mean resting QTcF > 470 msec obtained from a triplicate ECG",
            "criterions": [
                {
                    "exact_snippets": "Mean resting QTcF > 470 msec",
                    "criterion": "QTcF interval",
                    "requirements": [
                        {
                            "requirement_type": "mean value",
                            "expected_value": {
                                "operator": ">",
                                "value": 470,
                                "unit": "msec"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (eg, complete left bundle branch block, second- and third-degree heart block), or clinically significant sinus pause. Participants with controlled atrial fibrillation can be enrolled.",
            "criterions": [
                {
                    "exact_snippets": "clinically important abnormalities in rhythm, conduction, or morphology of resting ECG",
                    "criterion": "ECG abnormalities",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "complete left bundle branch block",
                    "criterion": "complete left bundle branch block",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "second- and third-degree heart block",
                    "criterion": "second- and third-degree heart block",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically significant sinus pause",
                    "criterion": "sinus pause",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "not clinically significant"
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants with controlled atrial fibrillation can be enrolled",
                    "criterion": "atrial fibrillation",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as symptomatic heart failure, hypokalemia, congenital long QT syndrome, immediate family history of long QT syndrome or unexplained sudden death at < 40 years of age. Hypertrophic cardiomyopathy and clinically significant stenotic valve disease.",
            "criterions": [
                {
                    "exact_snippets": "factors that increase the risk of QTc prolongation or risk of arrhythmic events",
                    "criterion": "risk of QTc prolongation or arrhythmic events",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "symptomatic heart failure",
                    "criterion": "symptomatic heart failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hypokalemia",
                    "criterion": "hypokalemia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "congenital long QT syndrome",
                    "criterion": "congenital long QT syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "immediate family history of long QT syndrome",
                    "criterion": "immediate family history of long QT syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "unexplained sudden death at < 40 years of age",
                    "criterion": "unexplained sudden death in family",
                    "requirements": [
                        {
                            "requirement_type": "age",
                            "expected_value": {
                                "operator": "<",
                                "value": 40,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Hypertrophic cardiomyopathy",
                    "criterion": "Hypertrophic cardiomyopathy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically significant stenotic valve disease",
                    "criterion": "clinically significant stenotic valve disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* LVEF < 50%, and/or experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, unstable angina pectoris, congestive heart failure NYHA Grade ≥ 2, cerebrovascular accident, or transient ischemic attack.",
            "criterions": [
                {
                    "exact_snippets": "LVEF < 50%",
                    "criterion": "LVEF",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft",
                    "criterion": "coronary artery bypass graft",
                    "requirements": [
                        {
                            "requirement_type": "experience",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "experience of any of the following procedures or conditions in the preceding 6 months: ... angioplasty",
                    "criterion": "angioplasty",
                    "requirements": [
                        {
                            "requirement_type": "experience",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "experience of any of the following procedures or conditions in the preceding 6 months: ... vascular stent",
                    "criterion": "vascular stent",
                    "requirements": [
                        {
                            "requirement_type": "experience",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "experience of any of the following procedures or conditions in the preceding 6 months: ... myocardial infarction",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "experience",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "experience of any of the following procedures or conditions in the preceding 6 months: ... unstable angina pectoris",
                    "criterion": "unstable angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "experience",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "experience of any of the following procedures or conditions in the preceding 6 months: ... congestive heart failure NYHA Grade ≥ 2",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "NYHA Grade",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "experience of any of the following procedures or conditions in the preceding 6 months: ... cerebrovascular accident",
                    "criterion": "cerebrovascular accident",
                    "requirements": [
                        {
                            "requirement_type": "experience",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "experience of any of the following procedures or conditions in the preceding 6 months: ... transient ischemic attack",
                    "criterion": "transient ischemic attack",
                    "requirements": [
                        {
                            "requirement_type": "experience",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled hypertension.",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled hypertension",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Refractory nausea and vomiting, uncontrolled chronic gastrointestinal diseases, or previous significant bowel resection that would preclude adequate absorption of IMP(s).",
            "criterions": [
                {
                    "exact_snippets": "Refractory nausea and vomiting",
                    "criterion": "nausea and vomiting",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "refractory"
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled chronic gastrointestinal diseases",
                    "criterion": "chronic gastrointestinal diseases",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "previous significant bowel resection",
                    "criterion": "bowel resection",
                    "requirements": [
                        {
                            "requirement_type": "significance",
                            "expected_value": "significant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of hypersensitivity to active or inactive excipients of AZD8421 or drugs with a similar chemical structure or class to AZD8421.",
            "criterions": [
                {
                    "exact_snippets": "History of hypersensitivity to active or inactive excipients of AZD8421",
                    "criterion": "hypersensitivity to excipients of AZD8421",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History of hypersensitivity to ... drugs with a similar chemical structure or class to AZD8421",
                    "criterion": "hypersensitivity to drugs with similar chemical structure or class to AZD8421",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Currently pregnant (confirmed with positive pregnancy test), breast feeding, or planning to become pregnant. Participants of childbearing potential must agree to use one highly effective contraceptive measure.",
            "criterions": [
                {
                    "exact_snippets": "Currently pregnant (confirmed with positive pregnancy test)",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breast feeding",
                    "criterion": "breastfeeding status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "planning to become pregnant",
                    "criterion": "pregnancy intention",
                    "requirements": [
                        {
                            "requirement_type": "intention",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Participants of childbearing potential must agree to use one highly effective contraceptive measure",
                    "criterion": "contraceptive use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [
        {
            "line": "* Inadequate bone marrow reserve or organ function as demonstrated by relevant laboratory values:",
            "criterions": [
                {
                    "exact_snippets": "Inadequate bone marrow reserve",
                    "criterion": "bone marrow reserve",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "inadequate ... organ function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Previous treatment with AZD8421 or with any CDK2-selective inhibitor, or protein kinase membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase 1 (PKMYT1) inhibitor, or WEE1 inhibitor.",
            "criterions": [
                {
                    "exact_snippets": "Previous treatment with AZD8421",
                    "criterion": "previous treatment with AZD8421",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "previous treatment with ... any CDK2-selective inhibitor",
                    "criterion": "previous treatment with CDK2-selective inhibitor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "previous treatment with ... protein kinase membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase 1 (PKMYT1) inhibitor",
                    "criterion": "previous treatment with PKMYT1 inhibitor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "previous treatment with ... WEE1 inhibitor",
                    "criterion": "previous treatment with WEE1 inhibitor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}