{
    "info": {
        "nct_id": "NCT03637491",
        "official_title": "A PHASE 1B/2 STUDY TO EVALUATE SAFETY AND CLINICAL ACTIVITY OF COMBINATIONS OF AVELUMAB, BINIMETINIB AND TALAZOPARIB IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC RAS-MUTANT SOLID TUMORS",
        "inclusion_criteria": "* Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors that are not amenable for treatment with curative intent as follows:\n\n  1. Metastatic pancreatic ductal adenocarcinoma; or\n  2. Phase 2 only: Stage IIIb/IV NSCLC or other advanced solid tumors with documented positive KRAS or NRAS mutation as determined using a validated test performed in a CAP/CLIA-certified laboratory (or other comparable local or regional certification).\n* Have had disease progression during or following at least 1 and not more than 2 prior lines of treatment for advanced or metastatic disease.\n* Patients with NSCLC must have previously received treatment with an anti-PD-1 or anti-PD-L1 agent for advanced disease.\n* Measurable disease as per RECIST v1.1 criteria.\n* Provision of a baseline tumor sample.\n* Age ≥18 years (Japanese patients must be ≥20 years old)\n* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.\n* Adequate bone marrow, renal and liver functions.\n* Adequate cardiac function.\n* Informed consent provided.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Prior treatment with avelumab, a PARP inhibitor or MEK inhibitor.\n* Prior systemic anti-cancer therapy within 2 weeks prior to study enrollment.\n* Persisting toxicity related to prior therapy.\n* Current use of immunosuppressive medication.\n* Known history of immune-mediated colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis, uveitis or iritis.\n* Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent.\n* Diagnosis of myelodysplastic syndrome (MDS).\n* Known symptomatic brain metastases requiring steroids.\n* Known history of testing positive for HIV or hepatitis.\n* Clinically significant (ie, active) cardiovascular disease.\n* History of thromboembolic or cerebrovascular events.\n* Current or anticipated use of a P-gp inhibitor, inducer, or inhibitor of breast cancer resistance protein (BCRP)\n* Uncontrolled hypertension.\n* Concurrent neuromuscular disorder that is associated with the potential of elevated creatinine kinase.\n* Known history of Gilbert's syndrome.\n* History or current evidence of retinal degenerative disease, retinal vein occlusion (RVO) or current risk factors for RVO.\n* Other acute or chronic medical or psychiatric condition.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors that are not amenable for treatment with curative intent as follows:",
            "criterions": [
                {
                    "exact_snippets": "Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors",
                    "criterion": "solid tumors",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": "histological"
                        },
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "locally advanced",
                                "metastatic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "not amenable for treatment with curative intent",
                    "criterion": "treatment amenability",
                    "requirements": [
                        {
                            "requirement_type": "curative intent",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Metastatic pancreatic ductal adenocarcinoma; or",
            "criterions": [
                {
                    "exact_snippets": "Metastatic pancreatic ductal adenocarcinoma",
                    "criterion": "pancreatic ductal adenocarcinoma",
                    "requirements": [
                        {
                            "requirement_type": "metastasis",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Phase 2 only: Stage IIIb/IV NSCLC or other advanced solid tumors with documented positive KRAS or NRAS mutation as determined using a validated test performed in a CAP/CLIA-certified laboratory (or other comparable local or regional certification).",
            "criterions": [
                {
                    "exact_snippets": "Stage IIIb/IV NSCLC or other advanced solid tumors",
                    "criterion": "cancer stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "Stage IIIb",
                                "Stage IV"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "documented positive KRAS or NRAS mutation",
                    "criterion": "KRAS or NRAS mutation",
                    "requirements": [
                        {
                            "requirement_type": "mutation status",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "as determined using a validated test performed in a CAP/CLIA-certified laboratory (or other comparable local or regional certification)",
                    "criterion": "mutation test validation",
                    "requirements": [
                        {
                            "requirement_type": "validation",
                            "expected_value": "CAP/CLIA-certified laboratory or comparable certification"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Have had disease progression during or following at least 1 and not more than 2 prior lines of treatment for advanced or metastatic disease.",
            "criterions": [
                {
                    "exact_snippets": "disease progression during or following at least 1 and not more than 2 prior lines of treatment",
                    "criterion": "disease progression",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "during or following"
                        },
                        {
                            "requirement_type": "treatment lines",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 1,
                                        "unit": "lines"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "lines"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with NSCLC must have previously received treatment with an anti-PD-1 or anti-PD-L1 agent for advanced disease.",
            "criterions": [
                {
                    "exact_snippets": "Patients with NSCLC",
                    "criterion": "NSCLC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "previously received treatment with an anti-PD-1 or anti-PD-L1 agent",
                    "criterion": "treatment with anti-PD-1 or anti-PD-L1 agent",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "for advanced disease",
                    "criterion": "advanced disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Measurable disease as per RECIST v1.1 criteria.",
            "criterions": [
                {
                    "exact_snippets": "Measurable disease as per RECIST v1.1 criteria",
                    "criterion": "disease",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": "RECIST v1.1 criteria"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Provision of a baseline tumor sample.",
            "criterions": [
                {
                    "exact_snippets": "Provision of a baseline tumor sample.",
                    "criterion": "baseline tumor sample",
                    "requirements": [
                        {
                            "requirement_type": "provision",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Age ≥18 years (Japanese patients must be ≥20 years old)",
            "criterions": [
                {
                    "exact_snippets": "Age ≥18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Japanese patients must be ≥20 years old",
                    "criterion": "age for Japanese patients",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 20,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.",
                    "criterion": "ECOG Performance Status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate cardiac function.",
            "criterions": [
                {
                    "exact_snippets": "Adequate cardiac function",
                    "criterion": "cardiac function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Informed consent provided.",
            "criterions": [
                {
                    "exact_snippets": "Informed consent provided",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "provision",
                            "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": "* Prior treatment with avelumab, a PARP inhibitor or MEK inhibitor.",
            "criterions": [
                {
                    "exact_snippets": "Prior treatment with avelumab",
                    "criterion": "prior treatment",
                    "requirements": [
                        {
                            "requirement_type": "drug",
                            "expected_value": "avelumab"
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with ... a PARP inhibitor",
                    "criterion": "prior treatment",
                    "requirements": [
                        {
                            "requirement_type": "drug class",
                            "expected_value": "PARP inhibitor"
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with ... MEK inhibitor",
                    "criterion": "prior treatment",
                    "requirements": [
                        {
                            "requirement_type": "drug class",
                            "expected_value": "MEK inhibitor"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior systemic anti-cancer therapy within 2 weeks prior to study enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Prior systemic anti-cancer therapy within 2 weeks prior to study enrollment.",
                    "criterion": "prior systemic anti-cancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Persisting toxicity related to prior therapy.",
            "criterions": [
                {
                    "exact_snippets": "Persisting toxicity related to prior therapy",
                    "criterion": "toxicity",
                    "requirements": [
                        {
                            "requirement_type": "persistence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "relation to prior therapy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Current use of immunosuppressive medication.",
            "criterions": [
                {
                    "exact_snippets": "Current use of immunosuppressive medication.",
                    "criterion": "immunosuppressive medication",
                    "requirements": [
                        {
                            "requirement_type": "current use",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known history of immune-mediated colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis, uveitis or iritis.",
            "criterions": [
                {
                    "exact_snippets": "Known history of immune-mediated colitis",
                    "criterion": "immune-mediated colitis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Known history of ... inflammatory bowel disease",
                    "criterion": "inflammatory bowel disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Known history of ... pneumonitis",
                    "criterion": "pneumonitis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Known history of ... pulmonary fibrosis",
                    "criterion": "pulmonary fibrosis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Known history of ... uveitis",
                    "criterion": "uveitis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Known history of ... iritis",
                    "criterion": "iritis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent.",
            "criterions": [
                {
                    "exact_snippets": "Active or prior autoimmune disease",
                    "criterion": "autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "might deteriorate when receiving an immunostimulatory agent",
                    "criterion": "deterioration risk with immunostimulatory agent",
                    "requirements": [
                        {
                            "requirement_type": "risk",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Diagnosis of myelodysplastic syndrome (MDS).",
            "criterions": [
                {
                    "exact_snippets": "Diagnosis of myelodysplastic syndrome (MDS)",
                    "criterion": "myelodysplastic syndrome (MDS)",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known symptomatic brain metastases requiring steroids.",
            "criterions": [
                {
                    "exact_snippets": "Known symptomatic brain metastases",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "requiring steroids",
                    "criterion": "steroid requirement",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known history of testing positive for HIV or hepatitis.",
            "criterions": [
                {
                    "exact_snippets": "Known history of testing positive for HIV",
                    "criterion": "HIV status",
                    "requirements": [
                        {
                            "requirement_type": "history of positive test",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Known history of testing positive for ... hepatitis",
                    "criterion": "hepatitis status",
                    "requirements": [
                        {
                            "requirement_type": "history of positive test",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Clinically significant (ie, active) cardiovascular disease.",
            "criterions": [
                {
                    "exact_snippets": "Clinically significant (ie, active) cardiovascular disease.",
                    "criterion": "cardiovascular disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "clinically significant"
                        },
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of thromboembolic or cerebrovascular events.",
            "criterions": [
                {
                    "exact_snippets": "History of thromboembolic ... events.",
                    "criterion": "thromboembolic events",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History of ... cerebrovascular events.",
                    "criterion": "cerebrovascular events",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Current or anticipated use of a P-gp inhibitor, inducer, or inhibitor of breast cancer resistance protein (BCRP)",
            "criterions": [
                {
                    "exact_snippets": "Current or anticipated use of a P-gp inhibitor",
                    "criterion": "P-gp inhibitor use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Current or anticipated use of a ... inducer",
                    "criterion": "P-gp inducer use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Current or anticipated use of a ... inhibitor of breast cancer resistance protein (BCRP)",
                    "criterion": "BCRP inhibitor use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled hypertension.",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled hypertension",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Concurrent neuromuscular disorder that is associated with the potential of elevated creatinine kinase.",
            "criterions": [
                {
                    "exact_snippets": "Concurrent neuromuscular disorder",
                    "criterion": "neuromuscular disorder",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "associated with the potential of elevated creatinine kinase",
                    "criterion": "elevated creatinine kinase",
                    "requirements": [
                        {
                            "requirement_type": "potential association",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known history of Gilbert's syndrome.",
            "criterions": [
                {
                    "exact_snippets": "Known history of Gilbert's syndrome",
                    "criterion": "Gilbert's syndrome",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History or current evidence of retinal degenerative disease, retinal vein occlusion (RVO) or current risk factors for RVO.",
            "criterions": [
                {
                    "exact_snippets": "History or current evidence of retinal degenerative disease",
                    "criterion": "retinal degenerative disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History or current evidence of ... retinal vein occlusion (RVO)",
                    "criterion": "retinal vein occlusion (RVO)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "current risk factors for RVO",
                    "criterion": "risk factors for retinal vein occlusion (RVO)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Other acute or chronic medical or psychiatric condition.",
            "criterions": [
                {
                    "exact_snippets": "acute or chronic medical or psychiatric condition",
                    "criterion": "medical or psychiatric condition",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "* Adequate bone marrow, renal and liver functions.",
            "criterions": [
                {
                    "exact_snippets": "Adequate bone marrow",
                    "criterion": "bone marrow function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "adequate ... renal",
                    "criterion": "renal function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "adequate ... liver functions",
                    "criterion": "liver function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}