{
    "info": {
        "nct_id": "NCT03658772",
        "official_title": "An Open-label, Single-arm, Phase 1b Study to Evaluate the Safety and Efficacy of Grapiprant (ARY-007) in Combination With Pembolizumab in Patients With Advanced or Progressive Microsatellite Stable (MSS) Colorectal Cancer (CRC)",
        "inclusion_criteria": "* Male and female adult patients 18 years of age or older on day of signing informed consent.\n* Patients must have a histologically confirmed advanced, metastatic, or progressive Microsatellite Stable (MSS) Colorectal Cancer (CRC) per institutional standards.\n* Patient has received at least two prior lines of therapy for advanced or metastatic CRC, at least one of which included fluorouracil.\n* Highly effective birth control.\n* Measurable disease.\n* Accessible tumor that can be safely accessed for multiple core biopsies and patient is willing to provide tissue from newly obtain biopsies before and during treatment.\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.\n* Adequate organ function.\n* Able to swallow and absorb oral tablets.\n\nKey\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor\n* Current use of NSAIDs, COX-2 inhibitors and aspirin products within 3 days (preferably 7 days) before treatment initiation or at anytime during the study unless used for management of AE.\n* History of severe hypersensitivity reactions to chimeric or humanized antibodies\n* Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to treatment, or 5 half-lives, whichever is shorter.\n* Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.\n* Known additional malignancy that is progressing or has required active treatment within the past 3 years.\n* Known active CNS metastases and/or carcinomatous meningitis.\n* Active autoimmune disease that has required systemic treatment in past 2 years.\n* History of non-infectious pneumonitis that required steroids or has current pneumonitis.\n* Active infection requiring systemic therapy.\n* Recent (within the last 12 months) or current GI ulcer, colitis or non-immune colitis.\n* Known history of human immunodeficiency virus (HIV) infection, Hepatitis B, or active Hepatitis C virus infection.\n* Clinically significant (i.e. active) cardiovascular disease\n* Allogeneic tissue/solid organ transplant\n* Medical conditions requiring concomitant administration of strong CYP3A4 or P glycoprotein inhibitors or inducers.",
        "miscellaneous_criteria": "Key"
    },
    "inclusion_lines": [
        {
            "line": "* Male and female adult patients 18 years of age or older on day of signing informed consent.",
            "criterions": [
                {
                    "exact_snippets": "Male and female adult patients",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "male",
                                "female"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "18 years of age or older",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have a histologically confirmed advanced, metastatic, or progressive Microsatellite Stable (MSS) Colorectal Cancer (CRC) per institutional standards.",
            "criterions": [
                {
                    "exact_snippets": "histologically confirmed",
                    "criterion": "histological confirmation",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "advanced, metastatic, or progressive",
                    "criterion": "cancer stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "advanced",
                                "metastatic",
                                "progressive"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Microsatellite Stable (MSS)",
                    "criterion": "microsatellite stability",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": "stable"
                        }
                    ]
                },
                {
                    "exact_snippets": "Colorectal Cancer (CRC)",
                    "criterion": "cancer type",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "Colorectal Cancer"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient has received at least two prior lines of therapy for advanced or metastatic CRC, at least one of which included fluorouracil.",
            "criterions": [
                {
                    "exact_snippets": "Patient has received at least two prior lines of therapy for advanced or metastatic CRC",
                    "criterion": "prior lines of therapy for advanced or metastatic CRC",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "lines"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "at least one of which included fluorouracil",
                    "criterion": "prior therapy including fluorouracil",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lines"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Highly effective birth control.",
            "criterions": [
                {
                    "exact_snippets": "Highly effective birth control",
                    "criterion": "birth control",
                    "requirements": [
                        {
                            "requirement_type": "effectiveness",
                            "expected_value": "highly effective"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Measurable disease.",
            "criterions": [
                {
                    "exact_snippets": "Measurable disease",
                    "criterion": "disease",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Accessible tumor that can be safely accessed for multiple core biopsies and patient is willing to provide tissue from newly obtain biopsies before and during treatment.",
            "criterions": [
                {
                    "exact_snippets": "Accessible tumor that can be safely accessed for multiple core biopsies",
                    "criterion": "tumor accessibility",
                    "requirements": [
                        {
                            "requirement_type": "accessibility",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patient is willing to provide tissue from newly obtain biopsies before and during treatment",
                    "criterion": "patient willingness to provide tissue",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* 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": "* Adequate organ function.",
            "criterions": [
                {
                    "exact_snippets": "Adequate organ function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Able to swallow and absorb oral tablets.",
            "criterions": [
                {
                    "exact_snippets": "Able to swallow",
                    "criterion": "swallowing ability",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "absorb oral tablets",
                    "criterion": "absorption of oral tablets",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Key",
            "criterions": [
                {
                    "exact_snippets": "Key",
                    "criterion": "key",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": "N/A"
                        }
                    ]
                }
            ]
        },
        {
            "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": "* Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor",
            "criterions": [
                {
                    "exact_snippets": "Prior therapy with an anti-PD-1",
                    "criterion": "prior therapy with anti-PD-1 agent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior therapy with an ... anti-PD-L1",
                    "criterion": "prior therapy with anti-PD-L1 agent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior therapy with an ... anti-PD-L2 agent",
                    "criterion": "prior therapy with anti-PD-L2 agent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior therapy with an ... agent directed to another stimulatory or co-inhibitory T-cell receptor",
                    "criterion": "prior therapy with agent directed to another stimulatory or co-inhibitory T-cell receptor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Current use of NSAIDs, COX-2 inhibitors and aspirin products within 3 days (preferably 7 days) before treatment initiation or at anytime during the study unless used for management of AE.",
            "criterions": [
                {
                    "exact_snippets": "Current use of NSAIDs",
                    "criterion": "NSAID use",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": "within 3 days before treatment initiation or at anytime during the study"
                        }
                    ]
                },
                {
                    "exact_snippets": "Current use of ... COX-2 inhibitors",
                    "criterion": "COX-2 inhibitor use",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": "within 3 days before treatment initiation or at anytime during the study"
                        }
                    ]
                },
                {
                    "exact_snippets": "Current use of ... aspirin products",
                    "criterion": "aspirin product use",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": "within 3 days before treatment initiation or at anytime during the study"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of severe hypersensitivity reactions to chimeric or humanized antibodies",
            "criterions": [
                {
                    "exact_snippets": "History of severe hypersensitivity reactions to chimeric or humanized antibodies",
                    "criterion": "hypersensitivity reactions",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        },
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "antibody type",
                            "expected_value": [
                                "chimeric",
                                "humanized"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to treatment, or 5 half-lives, whichever is shorter.",
            "criterions": [
                {
                    "exact_snippets": "Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to treatment, or 5 half-lives, whichever is shorter.",
                    "criterion": "prior systemic anticancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "half-lives"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.",
            "criterions": [
                {
                    "exact_snippets": "Diagnosis of immunodeficiency",
                    "criterion": "immunodeficiency",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "receiving chronic systemic steroid therapy ... exceeding 10 mg daily of prednisone equivalent",
                    "criterion": "chronic systemic steroid therapy",
                    "requirements": [
                        {
                            "requirement_type": "dosage",
                            "expected_value": {
                                "operator": ">",
                                "value": 10,
                                "unit": "mg daily of prednisone equivalent"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "receiving ... any other form of immunosuppressive therapy within 7 days prior the first dose of study drug",
                    "criterion": "immunosuppressive therapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 7 days prior the first dose of study drug"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known additional malignancy that is progressing or has required active treatment within the past 3 years.",
            "criterions": [
                {
                    "exact_snippets": "Known additional malignancy",
                    "criterion": "additional malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "is progressing",
                    "criterion": "additional malignancy progression",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "progressing"
                        }
                    ]
                },
                {
                    "exact_snippets": "has required active treatment within the past 3 years",
                    "criterion": "additional malignancy treatment",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known active CNS metastases and/or carcinomatous meningitis.",
            "criterions": [
                {
                    "exact_snippets": "Known active CNS metastases",
                    "criterion": "CNS metastases",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "carcinomatous meningitis",
                    "criterion": "carcinomatous meningitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active autoimmune disease that has required systemic treatment in past 2 years.",
            "criterions": [
                {
                    "exact_snippets": "Active autoimmune disease that has required systemic treatment in past 2 years.",
                    "criterion": "autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        },
                        {
                            "requirement_type": "treatment",
                            "expected_value": "systemic treatment in past 2 years"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of non-infectious pneumonitis that required steroids or has current pneumonitis.",
            "criterions": [
                {
                    "exact_snippets": "History of non-infectious pneumonitis that required steroids",
                    "criterion": "non-infectious pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "treatment",
                            "expected_value": "steroids"
                        }
                    ]
                },
                {
                    "exact_snippets": "current pneumonitis",
                    "criterion": "pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active infection requiring systemic therapy.",
            "criterions": [
                {
                    "exact_snippets": "Active infection requiring systemic therapy.",
                    "criterion": "active infection",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "systemic therapy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Recent (within the last 12 months) or current GI ulcer, colitis or non-immune colitis.",
            "criterions": [
                {
                    "exact_snippets": "Recent (within the last 12 months) or current GI ulcer",
                    "criterion": "GI ulcer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "recency",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 12,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Recent (within the last 12 months) or current ... colitis",
                    "criterion": "colitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "recency",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 12,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Recent (within the last 12 months) or current ... non-immune colitis",
                    "criterion": "non-immune colitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "recency",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 12,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known history of human immunodeficiency virus (HIV) infection, Hepatitis B, or active Hepatitis C virus infection.",
            "criterions": [
                {
                    "exact_snippets": "Known history of human immunodeficiency virus (HIV) infection",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Hepatitis B",
                    "criterion": "Hepatitis B infection",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active Hepatitis C virus infection",
                    "criterion": "Hepatitis C infection",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Clinically significant (i.e. active) cardiovascular disease",
            "criterions": [
                {
                    "exact_snippets": "Clinically significant (i.e. active) cardiovascular disease",
                    "criterion": "cardiovascular disease",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        },
                        {
                            "requirement_type": "clinical significance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Allogeneic tissue/solid organ transplant",
            "criterions": [
                {
                    "exact_snippets": "Allogeneic tissue/solid organ transplant",
                    "criterion": "allogeneic tissue/solid organ transplant",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Medical conditions requiring concomitant administration of strong CYP3A4 or P glycoprotein inhibitors or inducers.",
            "criterions": [
                {
                    "exact_snippets": "Medical conditions requiring concomitant administration of strong CYP3A4 or P glycoprotein inhibitors or inducers.",
                    "criterion": "medical conditions",
                    "requirements": [
                        {
                            "requirement_type": "concomitant administration",
                            "expected_value": [
                                "strong CYP3A4 inhibitors",
                                "strong CYP3A4 inducers",
                                "P glycoprotein inhibitors",
                                "P glycoprotein inducers"
                            ]
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [
        {
            "line": "Key",
            "criterions": [
                {
                    "exact_snippets": "Key",
                    "criterion": "key",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": "N/A"
                        }
                    ]
                }
            ]
        }
    ],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}