{
    "info": {
        "nct_id": "NCT05512182",
        "official_title": "An Open Label, Single-Arm, Multi-Center Phase II Study to Evaluate the Efficacy of Triplet Combination With Pembrolizumab, Neratinib, and Paclitaxel as a Second Line Treatment in Recurrent/Advanced Gastric Cancer Having Somatic Human Epidermal Growth Factor Receptor Family (EGFR, HER2, HER3, HER4) Mutations or HER2 Amplification/Overexpression",
        "inclusion_criteria": "1. Has provided written informed consent for the trial.\n2. Is male or female at least 19 years of age on the day of signing informed consent.\n3. Has a histologically or cytologically confirmed diagnosis of advanced or metastatic gastric adenocarcinoma (systemic metastasis or locally advanced unresectable gastric cancer). A subject must have previously received 1st line chemotherapy using fluoropyrimidine- or platinum-based regimen and showed progression.\n4. Has tumors with known activating EGFR, ERBB2, ERBB3, ERBB4 mutations or HER2 amplification by NGS, or HER2 overexpression by IHC or SISH/FISH\n5. Has a life expectancy of at least 3 months.\n6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.\n7. Have measurable or evaluable disease determined by RECIST 1.1.\n8. Is able to swallow and retain orally administered medication.\n9. Have adequate organ function as defined in the following table:\n\n   * white blood cells ≥3000/mm3 and neutrophils ≥1000/mm3\n   * platelets ≥100 000/µL\n   * hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L\n   * AST (SGOT) and ALT (SGPT) ≤3.0 × upper limit of normal (ULN) of the study site (or ≤5.0 × ULN in patients with liver metastases)\n   * total bilirubin ≤2.0 × ULN\n   * creatinine ≤1.5 × ULN or creatinine clearance >60 mL/min (either measured value or estimated value using the Cockcroft-Gault equation)\n10. Has failed in trastuzumab treatment for HER2-positive patients during 1st-line treatment or trastuzumab-naïve for HER2-negative patients measured by IHC or SISH/FISH.\n11. Has left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).\n12. A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 6 months after the last dose of study treatment and refrain from donating sperm during this period.\n13. A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:\n\n    1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3; OR\n    2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 6 months after the last dose of study treatment.\nHealthy volunteers allowed\nMust have minimum age of 19 Years\nMust have maximum age of 99 Years",
        "exclusion_criteria": "1. Have received second line or more of anticancer treatment (not including adjuvant chemotherapy).\n2. Have multiple cancers (with the exception of completely resected basal cell carcinoma, thyroid cancer, stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, and superficial bladder cancer, and any other cancers that have not recurred for at least 5 years).\n3. Have history of hypersensitivity to anti-HER2, immune-oncology drugs.\n4. Have brain or leptomeningeal metastases. Patients may be enrolled for the study if they are asymptomatic and require no treatment.\n5. Have a tumor with an activating KRAS co-mutation.\n6. Have a history of uncontrollable or significant cardiovascular disease meeting any of the following:\n\n   * myocardial infarction within 180 days before study enrolment\n   * uncontrollable angina pectoris within 180 days before study enrollment\n   * New York Heart Association (NYHA) Class III or IV congestive heart failure\n   * uncontrollable hypertension despite appropriate treatment (e.g., systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥90 mmHg lasting 24 hours or more) arrhythmia requiring treatment.\n7. Have active, unresolved systemic infection requiring treatment.\n8. Are contraindicated for pembrolizumab, neratinib, or paclitaxel, or have severe hypersensitivity (≥Grade 3) to any of those drugs and/or their excipients.\n9. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.\n10. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.\n11. Have undergone surgery (any surgery involving general anesthesia) within 28 days before study treatment.\n12. Have received radiotherapy for gastric cancer within 14 days before study treatment.\n13. Have received systemic chemotherapy within 14 days before study treatment.\n14. Have received biologic therapy ≤2 weeks or 5 half-lives (t1/2) of the agent used, whichever is shorter, prior to the start of treatment.\n15. Have a positive test result for human immunodeficiency virus-1 (HIV-1) antibody.\n16. Have hepatitis B surface protein (HBs) antigen and HBV titer >2000 IU/ml (10,000 copy/ml), or hepatitis C virus (HCV) antibody positive result.\n17. Are pregnant or breastfeeding, or possibly pregnant.\n18. Have any unresolved ≥Grade 2 toxicity (per CTCAE v5.0) from previous anti-cancer therapy at the time of enrollment such as neuropathy, except for alopecia.\n19. Are incapable of providing consent for specific reasons, such as concurrent dementia or unwilling for any reason to give consent or to comply with procedures/requirements of this protocol.\n20. Are otherwise inappropriate for this study in the investigator's or sub-investigator's opinion.\n21. Demonstrates a QTc interval >450 ms for men or >470 ms for women, or has known history of congenital QT-prolongation or Torsade de pointes (TdP).\n22. Have significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or ≥Grade 2 diarrhea [per CTCAE v5.0] of any etiology at baseline).",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Has provided written informed consent for the trial.",
            "criterions": [
                {
                    "exact_snippets": "Has provided written informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Is male or female at least 19 years of age on the day of signing informed consent.",
            "criterions": [
                {
                    "exact_snippets": "male or female",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "at least 19 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 19,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Has a histologically or cytologically confirmed diagnosis of advanced or metastatic gastric adenocarcinoma (systemic metastasis or locally advanced unresectable gastric cancer). A subject must have previously received 1st line chemotherapy using fluoropyrimidine- or platinum-based regimen and showed progression.",
            "criterions": [
                {
                    "exact_snippets": "histologically or cytologically confirmed diagnosis of advanced or metastatic gastric adenocarcinoma",
                    "criterion": "gastric adenocarcinoma diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        },
                        {
                            "requirement_type": "stage",
                            "expected_value": "advanced or metastatic"
                        }
                    ]
                },
                {
                    "exact_snippets": "previously received 1st line chemotherapy using fluoropyrimidine- or platinum-based regimen",
                    "criterion": "1st line chemotherapy regimen",
                    "requirements": [
                        {
                            "requirement_type": "regimen type",
                            "expected_value": [
                                "fluoropyrimidine-based",
                                "platinum-based"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "showed progression",
                    "criterion": "disease progression",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Has tumors with known activating EGFR, ERBB2, ERBB3, ERBB4 mutations or HER2 amplification by NGS, or HER2 overexpression by IHC or SISH/FISH",
            "criterions": [
                {
                    "exact_snippets": "Has tumors with known activating EGFR, ERBB2, ERBB3, ERBB4 mutations",
                    "criterion": "tumor mutations",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "EGFR",
                                "ERBB2",
                                "ERBB3",
                                "ERBB4"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "HER2 amplification by NGS",
                    "criterion": "HER2 amplification",
                    "requirements": [
                        {
                            "requirement_type": "detection method",
                            "expected_value": "NGS"
                        }
                    ]
                },
                {
                    "exact_snippets": "HER2 overexpression by IHC or SISH/FISH",
                    "criterion": "HER2 overexpression",
                    "requirements": [
                        {
                            "requirement_type": "detection method",
                            "expected_value": [
                                "IHC",
                                "SISH/FISH"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Has a life expectancy of at least 3 months.",
            "criterions": [
                {
                    "exact_snippets": "life expectancy of at least 3 months",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Have measurable or evaluable disease determined by RECIST 1.1.",
            "criterions": [
                {
                    "exact_snippets": "Have measurable or evaluable disease determined by RECIST 1.1.",
                    "criterion": "disease",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": [
                                "measurable",
                                "evaluable"
                            ]
                        },
                        {
                            "requirement_type": "determination method",
                            "expected_value": "RECIST 1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Is able to swallow and retain orally administered medication.",
            "criterions": [
                {
                    "exact_snippets": "able to swallow",
                    "criterion": "swallowing ability",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "retain orally administered medication",
                    "criterion": "retention of orally administered medication",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Have adequate organ function as defined in the following table:",
            "criterions": [
                {
                    "exact_snippets": "adequate organ function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* white blood cells ≥3000/mm3 and neutrophils ≥1000/mm3",
            "criterions": [
                {
                    "exact_snippets": "white blood cells ≥3000/mm3",
                    "criterion": "white blood cells",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3000,
                                "unit": "mm3"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "neutrophils ≥1000/mm3",
                    "criterion": "neutrophils",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1000,
                                "unit": "mm3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* platelets ≥100 000/µL",
            "criterions": [
                {
                    "exact_snippets": "platelets ≥100 000/µL",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100000,
                                "unit": "/µL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L",
            "criterions": [
                {
                    "exact_snippets": "hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 9.0,
                                        "unit": "g/dL"
                                    },
                                    {
                                        "operator": ">=",
                                        "value": 5.6,
                                        "unit": "mmol/L"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* AST (SGOT) and ALT (SGPT) ≤3.0 × upper limit of normal (ULN) of the study site (or ≤5.0 × ULN in patients with liver metastases)",
            "criterions": [
                {
                    "exact_snippets": "AST (SGOT) ... ≤3.0 × upper limit of normal (ULN) ... (or ≤5.0 × ULN in patients with liver metastases)",
                    "criterion": "AST (SGOT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "× ULN"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "level with liver metastases",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "× ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ALT (SGPT) ... ≤3.0 × upper limit of normal (ULN) ... (or ≤5.0 × ULN in patients with liver metastases)",
                    "criterion": "ALT (SGPT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "× ULN"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "level with liver metastases",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "× ULN"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* total bilirubin ≤2.0 × ULN",
            "criterions": [
                {
                    "exact_snippets": "total bilirubin ≤2.0 × ULN",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.0,
                                "unit": "× ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* creatinine ≤1.5 × ULN or creatinine clearance >60 mL/min (either measured value or estimated value using the Cockcroft-Gault equation)",
            "criterions": [
                {
                    "exact_snippets": "creatinine ≤1.5 × ULN",
                    "criterion": "creatinine level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "× ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinine clearance >60 mL/min",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "clearance",
                            "expected_value": {
                                "operator": ">",
                                "value": 60,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Has failed in trastuzumab treatment for HER2-positive patients during 1st-line treatment or trastuzumab-naïve for HER2-negative patients measured by IHC or SISH/FISH.",
            "criterions": [
                {
                    "exact_snippets": "trastuzumab treatment for HER2-positive patients during 1st-line treatment",
                    "criterion": "trastuzumab treatment failure",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "failed"
                        }
                    ]
                },
                {
                    "exact_snippets": "trastuzumab-naïve for HER2-negative patients",
                    "criterion": "trastuzumab treatment",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "naïve"
                        }
                    ]
                },
                {
                    "exact_snippets": "HER2-positive patients",
                    "criterion": "HER2 status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "HER2-negative patients",
                    "criterion": "HER2 status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "measured by IHC or SISH/FISH",
                    "criterion": "HER2 measurement method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "IHC",
                                "SISH/FISH"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Has left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).",
            "criterions": [
                {
                    "exact_snippets": "left ventricular ejection fraction (LVEF) ≥50%",
                    "criterion": "left ventricular ejection fraction (LVEF)",
                    "requirements": [
                        {
                            "requirement_type": "measurement",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 6 months after the last dose of study treatment and refrain from donating sperm during this period.",
            "criterions": [
                {
                    "exact_snippets": "A male participant",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "male"
                        }
                    ]
                },
                {
                    "exact_snippets": "must agree to use a contraception",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "refrain from donating sperm",
                    "criterion": "sperm donation",
                    "requirements": [
                        {
                            "requirement_type": "prohibition",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:",
            "criterions": [
                {
                    "exact_snippets": "female participant",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected gender",
                            "expected_value": "female"
                        }
                    ]
                },
                {
                    "exact_snippets": "not pregnant",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "pregnancy",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "not breastfeeding",
                    "criterion": "breastfeeding status",
                    "requirements": [
                        {
                            "requirement_type": "breastfeeding",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3; OR",
            "criterions": [
                {
                    "exact_snippets": "Not a woman of childbearing potential (WOCBP)",
                    "criterion": "woman of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 6 months after the last dose of study treatment.",
            "criterions": [
                {
                    "exact_snippets": "WOCBP",
                    "criterion": "woman of childbearing potential (WOCBP)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "agrees to follow the contraceptive guidance in Appendix 3",
                    "criterion": "contraceptive guidance adherence",
                    "requirements": [
                        {
                            "requirement_type": "adherence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "during the treatment period and for at least 6 months after the last dose of study treatment",
                    "criterion": "contraceptive guidance duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "during the treatment period and for at least 6 months after the last dose of study treatment"
                        }
                    ]
                }
            ]
        },
        {
            "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 19 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 19 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 19,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 99 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 99 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 99,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Have received second line or more of anticancer treatment (not including adjuvant chemotherapy).",
            "criterions": [
                {
                    "exact_snippets": "Have received second line or more of anticancer treatment",
                    "criterion": "anticancer treatment",
                    "requirements": [
                        {
                            "requirement_type": "lines of treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "lines"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "not including adjuvant chemotherapy",
                    "criterion": "adjuvant chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "inclusion",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Have multiple cancers (with the exception of completely resected basal cell carcinoma, thyroid cancer, stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, and superficial bladder cancer, and any other cancers that have not recurred for at least 5 years).",
            "criterions": [
                {
                    "exact_snippets": "Have multiple cancers",
                    "criterion": "multiple cancers",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "completely resected basal cell carcinoma",
                    "criterion": "basal cell carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "resection status",
                            "expected_value": "completely resected"
                        }
                    ]
                },
                {
                    "exact_snippets": "thyroid cancer",
                    "criterion": "thyroid cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "stage I squamous cell carcinoma",
                    "criterion": "squamous cell carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "I"
                        }
                    ]
                },
                {
                    "exact_snippets": "carcinoma in situ",
                    "criterion": "carcinoma in situ",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "intramucosal carcinoma",
                    "criterion": "intramucosal carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "superficial bladder cancer",
                    "criterion": "superficial bladder cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "cancers that have not recurred for at least 5 years",
                    "criterion": "cancer recurrence",
                    "requirements": [
                        {
                            "requirement_type": "recurrence",
                            "expected_value": {
                                "operator": ">=",
                                "value": 5,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Have history of hypersensitivity to anti-HER2, immune-oncology drugs.",
            "criterions": [
                {
                    "exact_snippets": "history of hypersensitivity to anti-HER2",
                    "criterion": "hypersensitivity to anti-HER2 drugs",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of hypersensitivity to ... immune-oncology drugs",
                    "criterion": "hypersensitivity to immune-oncology drugs",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Have brain or leptomeningeal metastases. Patients may be enrolled for the study if they are asymptomatic and require no treatment.",
            "criterions": [
                {
                    "exact_snippets": "Have brain or leptomeningeal metastases",
                    "criterion": "brain or leptomeningeal metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients may be enrolled for the study if they are asymptomatic",
                    "criterion": "symptoms of brain or leptomeningeal metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "require no treatment",
                    "criterion": "treatment for brain or leptomeningeal metastases",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Have a tumor with an activating KRAS co-mutation.",
            "criterions": [
                {
                    "exact_snippets": "Have a tumor",
                    "criterion": "tumor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "activating KRAS co-mutation",
                    "criterion": "KRAS co-mutation",
                    "requirements": [
                        {
                            "requirement_type": "activation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Have a history of uncontrollable or significant cardiovascular disease meeting any of the following:",
            "criterions": [
                {
                    "exact_snippets": "uncontrollable or significant cardiovascular disease",
                    "criterion": "cardiovascular disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "uncontrollable",
                                "significant"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* myocardial infarction within 180 days before study enrolment",
            "criterions": [
                {
                    "exact_snippets": "myocardial infarction within 180 days before study enrolment",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 180,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* uncontrollable angina pectoris within 180 days before study enrollment",
            "criterions": [
                {
                    "exact_snippets": "uncontrollable angina pectoris",
                    "criterion": "angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "uncontrollable"
                        }
                    ]
                },
                {
                    "exact_snippets": "within 180 days before study enrollment",
                    "criterion": "time since angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "time since",
                            "expected_value": {
                                "operator": "<=",
                                "value": 180,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* New York Heart Association (NYHA) Class III or IV congestive heart failure",
            "criterions": [
                {
                    "exact_snippets": "New York Heart Association (NYHA) Class III or IV congestive heart failure",
                    "criterion": "New York Heart Association (NYHA) class",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "III",
                                "IV"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* uncontrollable hypertension despite appropriate treatment (e.g., systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥90 mmHg lasting 24 hours or more) arrhythmia requiring treatment.",
            "criterions": [
                {
                    "exact_snippets": "uncontrollable hypertension despite appropriate treatment",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "systolic blood pressure ≥150 mmHg",
                    "criterion": "systolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 150,
                                "unit": "mmHg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "diastolic blood pressure ≥90 mmHg",
                    "criterion": "diastolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 90,
                                "unit": "mmHg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "arrhythmia requiring treatment",
                    "criterion": "arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Have active, unresolved systemic infection requiring treatment.",
            "criterions": [
                {
                    "exact_snippets": "active, unresolved systemic infection requiring treatment",
                    "criterion": "systemic infection",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "active"
                        },
                        {
                            "requirement_type": "resolution",
                            "expected_value": "unresolved"
                        },
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Are contraindicated for pembrolizumab, neratinib, or paclitaxel, or have severe hypersensitivity (≥Grade 3) to any of those drugs and/or their excipients.",
            "criterions": [
                {
                    "exact_snippets": "contraindicated for pembrolizumab",
                    "criterion": "contraindication",
                    "requirements": [
                        {
                            "requirement_type": "drug",
                            "expected_value": "pembrolizumab"
                        }
                    ]
                },
                {
                    "exact_snippets": "contraindicated for ... neratinib",
                    "criterion": "contraindication",
                    "requirements": [
                        {
                            "requirement_type": "drug",
                            "expected_value": "neratinib"
                        }
                    ]
                },
                {
                    "exact_snippets": "contraindicated for ... paclitaxel",
                    "criterion": "contraindication",
                    "requirements": [
                        {
                            "requirement_type": "drug",
                            "expected_value": "paclitaxel"
                        }
                    ]
                },
                {
                    "exact_snippets": "severe hypersensitivity (≥Grade 3) to any of those drugs",
                    "criterion": "hypersensitivity",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "Grade"
                            }
                        },
                        {
                            "requirement_type": "drug",
                            "expected_value": [
                                "pembrolizumab",
                                "neratinib",
                                "paclitaxel"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "severe hypersensitivity (≥Grade 3) to ... their excipients",
                    "criterion": "hypersensitivity",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "Grade"
                            }
                        },
                        {
                            "requirement_type": "substance",
                            "expected_value": "excipients"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.",
            "criterions": [
                {
                    "exact_snippets": "Has active autoimmune disease",
                    "criterion": "active autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "has required systemic treatment in the past 2 years",
                    "criterion": "systemic treatment for autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "past 2 years"
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.",
            "criterions": [
                {
                    "exact_snippets": "Has a history of (non-infectious) pneumonitis that required steroids",
                    "criterion": "history of non-infectious pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "steroids"
                        }
                    ]
                },
                {
                    "exact_snippets": "has current pneumonitis",
                    "criterion": "current pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Have undergone surgery (any surgery involving general anesthesia) within 28 days before study treatment.",
            "criterions": [
                {
                    "exact_snippets": "undergone surgery (any surgery involving general anesthesia) within 28 days before study treatment",
                    "criterion": "surgery involving general anesthesia",
                    "requirements": [
                        {
                            "requirement_type": "time since surgery",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Have received radiotherapy for gastric cancer within 14 days before study treatment.",
            "criterions": [
                {
                    "exact_snippets": "received radiotherapy for gastric cancer",
                    "criterion": "radiotherapy for gastric cancer",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 14,
                                "unit": "days before study treatment"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Have received systemic chemotherapy within 14 days before study treatment.",
            "criterions": [
                {
                    "exact_snippets": "Have received systemic chemotherapy within 14 days before study treatment.",
                    "criterion": "systemic chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Have received biologic therapy ≤2 weeks or 5 half-lives (t1/2) of the agent used, whichever is shorter, prior to the start of treatment.",
            "criterions": [
                {
                    "exact_snippets": "Have received biologic therapy ≤2 weeks or 5 half-lives (t1/2) of the agent used, whichever is shorter, prior to the start of treatment.",
                    "criterion": "biologic therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "half-lives"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Have a positive test result for human immunodeficiency virus-1 (HIV-1) antibody.",
            "criterions": [
                {
                    "exact_snippets": "positive test result for human immunodeficiency virus-1 (HIV-1) antibody",
                    "criterion": "HIV-1 antibody",
                    "requirements": [
                        {
                            "requirement_type": "test result",
                            "expected_value": "positive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Have hepatitis B surface protein (HBs) antigen and HBV titer >2000 IU/ml (10,000 copy/ml), or hepatitis C virus (HCV) antibody positive result.",
            "criterions": [
                {
                    "exact_snippets": "hepatitis B surface protein (HBs) antigen",
                    "criterion": "hepatitis B surface protein (HBs) antigen",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "HBV titer >2000 IU/ml (10,000 copy/ml)",
                    "criterion": "HBV titer",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 2000,
                                "unit": "IU/ml"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "hepatitis C virus (HCV) antibody positive result",
                    "criterion": "hepatitis C virus (HCV) antibody",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Are pregnant or breastfeeding, or possibly pregnant.",
            "criterions": [
                {
                    "exact_snippets": "Are pregnant",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "pregnant"
                        }
                    ]
                },
                {
                    "exact_snippets": "breastfeeding",
                    "criterion": "breastfeeding status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "breastfeeding"
                        }
                    ]
                },
                {
                    "exact_snippets": "possibly pregnant",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "possibly pregnant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "18. Have any unresolved ≥Grade 2 toxicity (per CTCAE v5.0) from previous anti-cancer therapy at the time of enrollment such as neuropathy, except for alopecia.",
            "criterions": [
                {
                    "exact_snippets": "unresolved ≥Grade 2 toxicity (per CTCAE v5.0) from previous anti-cancer therapy",
                    "criterion": "toxicity from previous anti-cancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "neuropathy",
                    "criterion": "neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "alopecia",
                    "criterion": "alopecia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "19. Are incapable of providing consent for specific reasons, such as concurrent dementia or unwilling for any reason to give consent or to comply with procedures/requirements of this protocol.",
            "criterions": [
                {
                    "exact_snippets": "incapable of providing consent",
                    "criterion": "consent capability",
                    "requirements": [
                        {
                            "requirement_type": "capability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "concurrent dementia",
                    "criterion": "dementia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unwilling for any reason to give consent",
                    "criterion": "willingness to give consent",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "unwilling for any reason ... to comply with procedures/requirements of this protocol",
                    "criterion": "willingness to comply with protocol",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "20. Are otherwise inappropriate for this study in the investigator's or sub-investigator's opinion.",
            "criterions": [
                {
                    "exact_snippets": "inappropriate for this study in the investigator's or sub-investigator's opinion",
                    "criterion": "appropriateness for study",
                    "requirements": [
                        {
                            "requirement_type": "opinion",
                            "expected_value": "appropriate"
                        }
                    ]
                }
            ]
        },
        {
            "line": "21. Demonstrates a QTc interval >450 ms for men or >470 ms for women, or has known history of congenital QT-prolongation or Torsade de pointes (TdP).",
            "criterions": [
                {
                    "exact_snippets": "QTc interval >450 ms for men",
                    "criterion": "QTc interval for men",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 450,
                                "unit": "ms"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "QTc interval ... >470 ms for women",
                    "criterion": "QTc interval for women",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 470,
                                "unit": "ms"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "known history of congenital QT-prolongation",
                    "criterion": "congenital QT-prolongation",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "known history of ... Torsade de pointes (TdP)",
                    "criterion": "Torsade de pointes (TdP)",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "22. Have significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or ≥Grade 2 diarrhea [per CTCAE v5.0] of any etiology at baseline).",
            "criterions": [
                {
                    "exact_snippets": "significant chronic gastrointestinal disorder",
                    "criterion": "chronic gastrointestinal disorder",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        }
                    ]
                },
                {
                    "exact_snippets": "diarrhea as a major symptom",
                    "criterion": "diarrhea",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Crohn's disease",
                    "criterion": "Crohn's disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "malabsorption",
                    "criterion": "malabsorption",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "≥Grade 2 diarrhea [per CTCAE v5.0]",
                    "criterion": "diarrhea severity",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "any etiology at baseline",
                    "criterion": "diarrhea etiology",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": "baseline"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}