{
    "info": {
        "nct_id": "NCT06328673",
        "official_title": "A First-in-Human Open-label, Phase 1a / 1b Dose Escalation and Expansion Cohort Study of DM919, a Novel Anti-MICA/B Antibody, as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors",
        "inclusion_criteria": "1. Provide a signed written informed consent form (ICF) before any study-specific assessment.\n2. Be at least 18 years old on the day of signing the ICF.\n3. Have a histologically confirmed advanced metastatic or unresectable, locally invasive solid cancer.\n\n   For monotherapy dose escalation cohorts from the 3mg/kg dose level, preferred indications include endometrial cancer, cervical cancer, non-small cell lung cancer, hepatocellular cancer, oral cavity cancer (parotid, salivary gland and others), HPV (+) laryngeal cancer and bile duct cancer. Other indications can be included as both sponsor and investigators agree.\n4. Have experienced progressive disease on at least one approved SOC systemic anti-cancer therapy for a given tumor type, or have been intolerant to SOC therapy, or in the opinion of the Investigator, have been considered ineligible for SOC therapy on medical grounds, or have no proven curative or life-prolonging approved SOC therapies available.\n5. Have at least one measurable tumor lesion per RECIST 1.1.\n6. Have a life expectancy of ≥3 months.\n7. Have an ECOG performance status of 0 or 1.\n8. Have adequate organ and bone marrow function.\n9. Female subjects must meet either of the following criteria:\n\n   1. Women of childbearing potential (WOCBP, defined as <12 continuous months of amenorrhea with no identified cause other than menopause, or not surgically sterile)\n   2. Postmenopausal or surgically sterile females.\n10. Male subjects with female partners of childbearing potential must agree to remain sexually abstinent or use condoms during the treatment period and for at least 120 days after the last dose of study treatments.\n11. Male subjects must agree to not donate or preserve sperm during the treatment period and for at least 120 days after the last dose of study treatments.\n12. Able and willing to comply with the protocol and the restrictions and assessments therein.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Received prior systemic anticancer treatment within 3 weeks before the first dose of study treatment (or 5 half-lives, whichever is shorter) or within 4 weeks before the first dose of study treatment in case of nitrosoureas or radio-immuno conjugate therapy.\n2. Current evidence of Grade ≥2 toxicity of prior therapy, except for any grade alopecia, Grade ≤2 peripheral neuropathy, and the following Grade ≤2 vitiligo, Grade ≤2 psoriasis not requiring systemic treatment and immune related Grade ≤2 endocrine disorders adequately managed by hormonal replacement therapy.\n3. Any history of discontinuation from prior therapy with anti-PD-1 or anti-PD-L1 inhibitor due to drug-related toxicity.\n4. Major surgery within 7 days before the first dose of study treatment or planned after the start of treatment, where 'major' is defined as any surgical procedure that requires more than 24 hours admission in a hospital.\n5. Radiotherapy within 2 weeks before the first dose of study treatment.\n6. Current evidence of symptomatic central nervous system (CNS) metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Symptomatic treated brain metastases are allowed if subjects are clinically stable in the judgement of the investigator.\n7. Other primary malignancy histologically different than the cancer under study, that has required active treatment within 2 years before the first dose of study treatment or may require active treatment during the treatment period.\n8. Any history of severe hypersensitivity to monoclonal antibodies or another form of severe hypersensitivity.\n9. Grade ≥3 viral, bacterial, or fungal infection within 2 weeks before the first dose of study treatment.\n10. Known active HIV infection, as determined by detectable HIV-RNA viral load.\n\n    a.Subjects on stable HAART therapy with undetectable HIV-RNA viral load and normal CD4 counts for at least 6 months before the first dose of study treatment are eligible.\n11. Known active HBV infection, as determined by detectable HBV-DNA viral load.\n12. Known active HCV infection, as determined by detectable HCV-RNA viral load.\n13. Known active or latent tuberculosis (TB). Testing for TB is not required at screening.\n14. Known active SARS-CoV-2 (COVID-19) infection, as determined by a positive COVID-19 test result within 2 weeks before the first dose of study treatment.\n15. Received a live or live-attenuated vaccine within 4 weeks before the first dose of study treatment. Injectable influenza vaccine and COVID-19 vaccine are permitted\n16. Uncontrolled or significant cardiovascular disease.\n17. Autoimmune disease that has required systemic treatment (i.e., disease modifying agents, corticosteroids above physiological doses [>10 mg daily of prednisone or equivalent] or immunosuppressive drugs) within 2 years before the first dose of study treatment.\n18. Any history of interstitial lung disease (ILD, including pneumonitis) that required systemic corticosteroid therapy.\n19. Diagnosis of immunodeficiency or receiving chronic systemic corticosteroid therapy at doses >10 mg daily of prednisone or equivalent or any other form of immunosuppressive therapy within 14 days before the first dose of study treatment.\n20. Had an allogeneic solid organ or stem cell transplant.\n21. Received systemic corticosteroid use at doses >10 mg daily of prednisone or equivalent within 2 weeks before the first dose of study treatment or other systemic immunosuppressive agents within 4 weeks before the first dose of study treatment.\n22. Received hematopoietic growth factors (G-SCF, GM-CSF, EPO) or transfusion of blood components (RBC or platelets) within 2 weeks before the first dose of study treatment, or likely to require treatment with these agents during Cycle 1.\n23. Pregnant or breastfeeding women.\n24. History or clinical evidence of any surgical or medical condition that the Investigator judges as likely to interfere with the results of the study or pose an additional risk to study subjects, such as rapidly progressive or uncontrolled disease involving a major organ system (e.g., disorders of vascular, cardiac, pulmonary, gastrointestinal, gynecologic, hematologic, neurologic, neoplastic, renal, endocrine, autoimmune or an immunodeficiency, or clinically significant active psychiatric or abuse disorders).\n25. History of chronic substance abuse within 12 months of the start of treatment.\n26. Sensitive substrates of cytochrome P450 enzymes should be excluded within 2 weeks (or 5 half-lives of the agent, whichever is longer) before the start of dosing in Phase 1a Dose Escalation part of the study.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Provide a signed written informed consent form (ICF) before any study-specific assessment.",
            "criterions": [
                {
                    "exact_snippets": "signed written informed consent form (ICF)",
                    "criterion": "informed consent form",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Be at least 18 years old on the day of signing the ICF.",
            "criterions": [
                {
                    "exact_snippets": "Be at least 18 years old",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Have a histologically confirmed advanced metastatic or unresectable, locally invasive solid cancer.",
            "criterions": [
                {
                    "exact_snippets": "histologically confirmed",
                    "criterion": "cancer diagnosis confirmation",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "histological"
                        }
                    ]
                },
                {
                    "exact_snippets": "advanced metastatic or unresectable, locally invasive solid cancer",
                    "criterion": "cancer type and stage",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "solid cancer"
                        },
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "advanced metastatic",
                                "unresectable",
                                "locally invasive"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "For monotherapy dose escalation cohorts from the 3mg/kg dose level, preferred indications include endometrial cancer, cervical cancer, non-small cell lung cancer, hepatocellular cancer, oral cavity cancer (parotid, salivary gland and others), HPV (+) laryngeal cancer and bile duct cancer. Other indications can be included as both sponsor and investigators agree.",
            "criterions": [
                {
                    "exact_snippets": "endometrial cancer",
                    "criterion": "endometrial cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "cervical cancer",
                    "criterion": "cervical cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "non-small cell lung cancer",
                    "criterion": "non-small cell lung cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hepatocellular cancer",
                    "criterion": "hepatocellular cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "oral cavity cancer (parotid, salivary gland and others)",
                    "criterion": "oral cavity cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "HPV (+) laryngeal cancer",
                    "criterion": "HPV (+) laryngeal cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "bile duct cancer",
                    "criterion": "bile duct cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Have experienced progressive disease on at least one approved SOC systemic anti-cancer therapy for a given tumor type, or have been intolerant to SOC therapy, or in the opinion of the Investigator, have been considered ineligible for SOC therapy on medical grounds, or have no proven curative or life-prolonging approved SOC therapies available.",
            "criterions": [
                {
                    "exact_snippets": "Have experienced progressive disease on at least one approved SOC systemic anti-cancer therapy",
                    "criterion": "progressive disease on SOC therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "have been intolerant to SOC therapy",
                    "criterion": "intolerance to SOC therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "in the opinion of the Investigator, have been considered ineligible for SOC therapy on medical grounds",
                    "criterion": "ineligibility for SOC therapy on medical grounds",
                    "requirements": [
                        {
                            "requirement_type": "opinion",
                            "expected_value": "Investigator"
                        }
                    ]
                },
                {
                    "exact_snippets": "have no proven curative or life-prolonging approved SOC therapies available",
                    "criterion": "availability of curative or life-prolonging SOC therapies",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Have at least one measurable tumor lesion per RECIST 1.1.",
            "criterions": [
                {
                    "exact_snippets": "at least one measurable tumor lesion per RECIST 1.1",
                    "criterion": "measurable tumor lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        },
                        {
                            "requirement_type": "standard",
                            "expected_value": "RECIST 1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Have a life expectancy of ≥3 months.",
            "criterions": [
                {
                    "exact_snippets": "life expectancy of ≥3 months",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Have an ECOG performance status of 0 or 1.",
            "criterions": [
                {
                    "exact_snippets": "ECOG performance status of 0 or 1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Have adequate organ and bone marrow function.",
            "criterions": [
                {
                    "exact_snippets": "adequate organ ... function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "adequate ... bone marrow function",
                    "criterion": "bone marrow function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Female subjects must meet either of the following criteria:",
            "criterions": [
                {
                    "exact_snippets": "Female subjects",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": "female"
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Women of childbearing potential (WOCBP, defined as <12 continuous months of amenorrhea with no identified cause other than menopause, or not surgically sterile)",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential (WOCBP, defined as <12 continuous months of amenorrhea with no identified cause other than menopause, or not surgically sterile)",
                    "criterion": "women of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "definition",
                            "expected_value": "<12 continuous months of amenorrhea with no identified cause other than menopause, or not surgically sterile"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Postmenopausal or surgically sterile females.",
            "criterions": [
                {
                    "exact_snippets": "Postmenopausal",
                    "criterion": "menopausal status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "postmenopausal"
                        }
                    ]
                },
                {
                    "exact_snippets": "surgically sterile females",
                    "criterion": "surgical sterility",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "surgically sterile"
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Male subjects with female partners of childbearing potential must agree to remain sexually abstinent or use condoms during the treatment period and for at least 120 days after the last dose of study treatments.",
            "criterions": [
                {
                    "exact_snippets": "Male subjects",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected gender",
                            "expected_value": "male"
                        }
                    ]
                },
                {
                    "exact_snippets": "female partners of childbearing potential",
                    "criterion": "partner's childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "childbearing potential",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must agree to remain sexually abstinent or use condoms during the treatment period and for at least 120 days after the last dose of study treatments",
                    "criterion": "sexual activity",
                    "requirements": [
                        {
                            "requirement_type": "abstinence or condom use",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Male subjects must agree to not donate or preserve sperm during the treatment period and for at least 120 days after the last dose of study treatments.",
            "criterions": [
                {
                    "exact_snippets": "Male subjects must agree to not donate or preserve sperm during the treatment period and for at least 120 days after the last dose of study treatments.",
                    "criterion": "sperm donation or preservation",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": "during the treatment period and for at least 120 days after the last dose of study treatments"
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Able and willing to comply with the protocol and the restrictions and assessments therein.",
            "criterions": [
                {
                    "exact_snippets": "Able and willing to comply with the protocol and the restrictions and assessments therein.",
                    "criterion": "compliance with protocol",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Received prior systemic anticancer treatment within 3 weeks before the first dose of study treatment (or 5 half-lives, whichever is shorter) or within 4 weeks before the first dose of study treatment in case of nitrosoureas or radio-immuno conjugate therapy.",
            "criterions": [
                {
                    "exact_snippets": "Received prior systemic anticancer treatment within 3 weeks before the first dose of study treatment (or 5 half-lives, whichever is shorter)",
                    "criterion": "prior systemic anticancer treatment",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 3,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Received prior systemic anticancer treatment ... within 4 weeks before the first dose of study treatment in case of nitrosoureas or radio-immuno conjugate therapy",
                    "criterion": "prior nitrosoureas or radio-immuno conjugate therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Current evidence of Grade ≥2 toxicity of prior therapy, except for any grade alopecia, Grade ≤2 peripheral neuropathy, and the following Grade ≤2 vitiligo, Grade ≤2 psoriasis not requiring systemic treatment and immune related Grade ≤2 endocrine disorders adequately managed by hormonal replacement therapy.",
            "criterions": [
                {
                    "exact_snippets": "Current evidence of Grade ≥2 toxicity of prior therapy",
                    "criterion": "toxicity of prior therapy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except for any grade alopecia",
                    "criterion": "alopecia",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "any grade"
                        }
                    ]
                },
                {
                    "exact_snippets": "Grade ≤2 peripheral neuropathy",
                    "criterion": "peripheral neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Grade ≤2 vitiligo",
                    "criterion": "vitiligo",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Grade ≤2 psoriasis not requiring systemic treatment",
                    "criterion": "psoriasis",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "Grade"
                            }
                        },
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "immune related Grade ≤2 endocrine disorders adequately managed by hormonal replacement therapy",
                    "criterion": "immune related endocrine disorders",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "Grade"
                            }
                        },
                        {
                            "requirement_type": "management",
                            "expected_value": "adequately managed by hormonal replacement therapy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Any history of discontinuation from prior therapy with anti-PD-1 or anti-PD-L1 inhibitor due to drug-related toxicity.",
            "criterions": [
                {
                    "exact_snippets": "Any history of discontinuation from prior therapy with anti-PD-1 or anti-PD-L1 inhibitor due to drug-related toxicity.",
                    "criterion": "discontinuation from prior therapy with anti-PD-1 or anti-PD-L1 inhibitor",
                    "requirements": [
                        {
                            "requirement_type": "cause",
                            "expected_value": "drug-related toxicity"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Major surgery within 7 days before the first dose of study treatment or planned after the start of treatment, where 'major' is defined as any surgical procedure that requires more than 24 hours admission in a hospital.",
            "criterions": [
                {
                    "exact_snippets": "Major surgery within 7 days before the first dose of study treatment",
                    "criterion": "major surgery",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 7 days before the first dose of study treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "planned after the start of treatment",
                    "criterion": "major surgery",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "planned after the start of treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "'major' is defined as any surgical procedure that requires more than 24 hours admission in a hospital",
                    "criterion": "major surgery",
                    "requirements": [
                        {
                            "requirement_type": "definition",
                            "expected_value": "any surgical procedure that requires more than 24 hours admission in a hospital"
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Radiotherapy within 2 weeks before the first dose of study treatment.",
            "criterions": [
                {
                    "exact_snippets": "Radiotherapy within 2 weeks before the first dose of study treatment.",
                    "criterion": "radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Current evidence of symptomatic central nervous system (CNS) metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Symptomatic treated brain metastases are allowed if subjects are clinically stable in the judgement of the investigator.",
            "criterions": [
                {
                    "exact_snippets": "Current evidence of symptomatic central nervous system (CNS) metastases",
                    "criterion": "symptomatic CNS metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Current evidence of ... leptomeningeal carcinomatosis",
                    "criterion": "leptomeningeal carcinomatosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Current evidence of ... untreated spinal cord compression",
                    "criterion": "untreated spinal cord compression",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Symptomatic treated brain metastases ... clinically stable in the judgement of the investigator",
                    "criterion": "symptomatic treated brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "clinical stability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Other primary malignancy histologically different than the cancer under study, that has required active treatment within 2 years before the first dose of study treatment or may require active treatment during the treatment period.",
            "criterions": [
                {
                    "exact_snippets": "Other primary malignancy histologically different than the cancer under study",
                    "criterion": "other primary malignancy",
                    "requirements": [
                        {
                            "requirement_type": "histological difference",
                            "expected_value": "different than the cancer under study"
                        }
                    ]
                },
                {
                    "exact_snippets": "has required active treatment within 2 years before the first dose of study treatment",
                    "criterion": "active treatment for other primary malignancy",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "may require active treatment during the treatment period",
                    "criterion": "active treatment for other primary malignancy",
                    "requirements": [
                        {
                            "requirement_type": "potential future treatment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Any history of severe hypersensitivity to monoclonal antibodies or another form of severe hypersensitivity.",
            "criterions": [
                {
                    "exact_snippets": "Any history of severe hypersensitivity to monoclonal antibodies",
                    "criterion": "hypersensitivity to monoclonal antibodies",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                },
                {
                    "exact_snippets": "another form of severe hypersensitivity",
                    "criterion": "hypersensitivity",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Grade ≥3 viral, bacterial, or fungal infection within 2 weeks before the first dose of study treatment.",
            "criterions": [
                {
                    "exact_snippets": "Grade ≥3 viral, bacterial, or fungal infection",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "grade"
                            }
                        },
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "viral",
                                "bacterial",
                                "fungal"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "within 2 weeks before the first dose of study treatment",
                    "criterion": "time since infection",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Known active HIV infection, as determined by detectable HIV-RNA viral load.",
            "criterions": [
                {
                    "exact_snippets": "Known active HIV infection, as determined by detectable HIV-RNA viral load.",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "active"
                        },
                        {
                            "requirement_type": "detection method",
                            "expected_value": "HIV-RNA viral load"
                        }
                    ]
                }
            ]
        },
        {
            "line": "a.Subjects on stable HAART therapy with undetectable HIV-RNA viral load and normal CD4 counts for at least 6 months before the first dose of study treatment are eligible.",
            "criterions": [
                {
                    "exact_snippets": "Subjects on stable HAART therapy",
                    "criterion": "HAART therapy",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "undetectable HIV-RNA viral load",
                    "criterion": "HIV-RNA viral load",
                    "requirements": [
                        {
                            "requirement_type": "detectability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "normal CD4 counts",
                    "criterion": "CD4 counts",
                    "requirements": [
                        {
                            "requirement_type": "normality",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "for at least 6 months before the first dose of study treatment",
                    "criterion": "duration of stable condition",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Known active HBV infection, as determined by detectable HBV-DNA viral load.",
            "criterions": [
                {
                    "exact_snippets": "Known active HBV infection, as determined by detectable HBV-DNA viral load.",
                    "criterion": "HBV infection",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "active"
                        },
                        {
                            "requirement_type": "detection",
                            "expected_value": "detectable HBV-DNA viral load"
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Known active HCV infection, as determined by detectable HCV-RNA viral load.",
            "criterions": [
                {
                    "exact_snippets": "Known active HCV infection, as determined by detectable HCV-RNA viral load.",
                    "criterion": "HCV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Known active or latent tuberculosis (TB). Testing for TB is not required at screening.",
            "criterions": [
                {
                    "exact_snippets": "Known active or latent tuberculosis (TB)",
                    "criterion": "tuberculosis (TB)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Known active SARS-CoV-2 (COVID-19) infection, as determined by a positive COVID-19 test result within 2 weeks before the first dose of study treatment.",
            "criterions": [
                {
                    "exact_snippets": "Known active SARS-CoV-2 (COVID-19) infection, as determined by a positive COVID-19 test result",
                    "criterion": "SARS-CoV-2 (COVID-19) infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "positive COVID-19 test result within 2 weeks before the first dose of study treatment",
                    "criterion": "COVID-19 test result",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "positive"
                        },
                        {
                            "requirement_type": "timeframe",
                            "expected_value": "within 2 weeks before the first dose of study treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Received a live or live-attenuated vaccine within 4 weeks before the first dose of study treatment. Injectable influenza vaccine and COVID-19 vaccine are permitted",
            "criterions": [
                {
                    "exact_snippets": "Received a live or live-attenuated vaccine within 4 weeks before the first dose of study treatment",
                    "criterion": "live or live-attenuated vaccine",
                    "requirements": [
                        {
                            "requirement_type": "time since administration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Injectable influenza vaccine and COVID-19 vaccine are permitted",
                    "criterion": "injectable influenza vaccine",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Injectable influenza vaccine and COVID-19 vaccine are permitted",
                    "criterion": "COVID-19 vaccine",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Uncontrolled or significant cardiovascular disease.",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled or significant cardiovascular disease",
                    "criterion": "cardiovascular disease",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Autoimmune disease that has required systemic treatment (i.e., disease modifying agents, corticosteroids above physiological doses [>10 mg daily of prednisone or equivalent] or immunosuppressive drugs) within 2 years before the first dose of study treatment.",
            "criterions": [
                {
                    "exact_snippets": "Autoimmune disease that has required systemic treatment",
                    "criterion": "autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "systemic treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "corticosteroids above physiological doses [>10 mg daily of prednisone or equivalent]",
                    "criterion": "corticosteroid dosage",
                    "requirements": [
                        {
                            "requirement_type": "dosage",
                            "expected_value": {
                                "operator": ">",
                                "value": 10,
                                "unit": "mg daily of prednisone or equivalent"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "within 2 years before the first dose of study treatment",
                    "criterion": "treatment timeframe",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "18. Any history of interstitial lung disease (ILD, including pneumonitis) that required systemic corticosteroid therapy.",
            "criterions": [
                {
                    "exact_snippets": "Any history of interstitial lung disease (ILD, including pneumonitis)",
                    "criterion": "interstitial lung disease (ILD, including pneumonitis)",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "required systemic corticosteroid therapy",
                    "criterion": "systemic corticosteroid therapy",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "19. Diagnosis of immunodeficiency or receiving chronic systemic corticosteroid therapy at doses >10 mg daily of prednisone or equivalent or any other form of immunosuppressive therapy within 14 days before the first dose of study treatment.",
            "criterions": [
                {
                    "exact_snippets": "Diagnosis of immunodeficiency",
                    "criterion": "immunodeficiency",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "receiving chronic systemic corticosteroid therapy at doses >10 mg daily of prednisone or equivalent",
                    "criterion": "chronic systemic corticosteroid therapy",
                    "requirements": [
                        {
                            "requirement_type": "dose",
                            "expected_value": {
                                "operator": ">",
                                "value": 10,
                                "unit": "mg daily of prednisone or equivalent"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "any other form of immunosuppressive therapy within 14 days before the first dose of study treatment",
                    "criterion": "immunosuppressive therapy",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 14 days before the first dose of study treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "20. Had an allogeneic solid organ or stem cell transplant.",
            "criterions": [
                {
                    "exact_snippets": "Had an allogeneic solid organ or stem cell transplant.",
                    "criterion": "allogeneic solid organ transplant",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Had an allogeneic solid organ or stem cell transplant.",
                    "criterion": "allogeneic stem cell transplant",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "21. Received systemic corticosteroid use at doses >10 mg daily of prednisone or equivalent within 2 weeks before the first dose of study treatment or other systemic immunosuppressive agents within 4 weeks before the first dose of study treatment.",
            "criterions": [
                {
                    "exact_snippets": "systemic corticosteroid use at doses >10 mg daily of prednisone or equivalent within 2 weeks before the first dose of study treatment",
                    "criterion": "systemic corticosteroid use",
                    "requirements": [
                        {
                            "requirement_type": "dose",
                            "expected_value": {
                                "operator": ">",
                                "value": 10,
                                "unit": "mg daily of prednisone or equivalent"
                            }
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 2 weeks before the first dose of study treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "other systemic immunosuppressive agents within 4 weeks before the first dose of study treatment",
                    "criterion": "systemic immunosuppressive agents",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 4 weeks before the first dose of study treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "22. Received hematopoietic growth factors (G-SCF, GM-CSF, EPO) or transfusion of blood components (RBC or platelets) within 2 weeks before the first dose of study treatment, or likely to require treatment with these agents during Cycle 1.",
            "criterions": [
                {
                    "exact_snippets": "Received hematopoietic growth factors (G-SCF, GM-CSF, EPO)",
                    "criterion": "hematopoietic growth factors",
                    "requirements": [
                        {
                            "requirement_type": "receipt",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "transfusion of blood components (RBC or platelets)",
                    "criterion": "transfusion of blood components",
                    "requirements": [
                        {
                            "requirement_type": "receipt",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "likely to require treatment with these agents during Cycle 1",
                    "criterion": "requirement of treatment with hematopoietic growth factors or blood components",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "23. Pregnant or breastfeeding women.",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breastfeeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "24. History or clinical evidence of any surgical or medical condition that the Investigator judges as likely to interfere with the results of the study or pose an additional risk to study subjects, such as rapidly progressive or uncontrolled disease involving a major organ system (e.g., disorders of vascular, cardiac, pulmonary, gastrointestinal, gynecologic, hematologic, neurologic, neoplastic, renal, endocrine, autoimmune or an immunodeficiency, or clinically significant active psychiatric or abuse disorders).",
            "criterions": [
                {
                    "exact_snippets": "History or clinical evidence of any surgical or medical condition",
                    "criterion": "surgical or medical condition",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "rapidly progressive or uncontrolled disease involving a major organ system",
                    "criterion": "disease involving a major organ system",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": "rapidly progressive"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "disorders of vascular, cardiac, pulmonary, gastrointestinal, gynecologic, hematologic, neurologic, neoplastic, renal, endocrine, autoimmune or an immunodeficiency",
                    "criterion": "disorders of major organ systems",
                    "requirements": [
                        {
                            "requirement_type": "types",
                            "expected_value": [
                                "vascular",
                                "cardiac",
                                "pulmonary",
                                "gastrointestinal",
                                "gynecologic",
                                "hematologic",
                                "neurologic",
                                "neoplastic",
                                "renal",
                                "endocrine",
                                "autoimmune",
                                "immunodeficiency"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically significant active psychiatric or abuse disorders",
                    "criterion": "psychiatric or abuse disorders",
                    "requirements": [
                        {
                            "requirement_type": "clinical significance",
                            "expected_value": "clinically significant"
                        },
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "25. History of chronic substance abuse within 12 months of the start of treatment.",
            "criterions": [
                {
                    "exact_snippets": "History of chronic substance abuse within 12 months",
                    "criterion": "chronic substance abuse",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 12,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "26. Sensitive substrates of cytochrome P450 enzymes should be excluded within 2 weeks (or 5 half-lives of the agent, whichever is longer) before the start of dosing in Phase 1a Dose Escalation part of the study.",
            "criterions": [
                {
                    "exact_snippets": "Sensitive substrates of cytochrome P450 enzymes should be excluded",
                    "criterion": "sensitive substrates of cytochrome P450 enzymes",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "within 2 weeks (or 5 half-lives of the agent, whichever is longer) before the start of dosing",
                    "criterion": "timeframe for exclusion",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": "5 half-lives of the agent"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}