{
    "info": {
        "nct_id": "NCT03871348",
        "official_title": "A Phase 1 First-in-Human Dose Escalation and Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR441000 Administered Intratumorally as Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors",
        "inclusion_criteria": "Healthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "",
        "miscellaneous_criteria": "Inclusion criteria:\n\n* At least 18 years of age\n* Advanced solid tumors including lymphomas for which no standard alternative therapy is available (escalation phase).\n* Advanced melanoma (Stage IIIB-C or Stage IV, anti-PD-1/PD-L1 treated or not) or anti-PD-1/PD-L1 not treated advanced Head and Neck Squamous Cell Cancer or anti-PD-1/PD-L1 not treated Advanced Cutaneous Squamous Cell Cancer where no other alternative treatment option exists (expansion phases).\n* Minimum 3 lesions enrollment.\n* Injectable disease (i.e., suitable for direct intratumoral injection based on the dose level volume of each cohort and cumulative lesion size; according to the investigator's judgement).\n* A lesion amenable for additional tumor biopsy.\n* Patients with measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.\n* Life expectancy more than 3 months.\n* Willingness to provide mandatory tumor biopsy.\n* Male and female patients who agree to use effective contraceptive methods.\n* Signed informed consent.\n\nExclusion criteria:\n\n* Eastern Cooperative Oncology Group (ECOG) performance score >1.\n* Significant and uncontrolled concomitant illness that would adversely affect the patient's participation in the study.\n* Any prior organ transplantation.\n* History within the last 5 years of an invasive malignancy other than the one treated in this study, with the exception of resected basal or squamous-cell skin cancer or carcinoma, in situ of cervix or other local tumors considered cured by local treatment.\n* History of unresolved viral hepatitis; systemic immune suppression including acquired immunodeficiency syndrome (AIDS) related illnesses or human immunodeficiency virus (HIV) disease requiring antiretroviral treatment.\n* Prior splenectomy.\n* New and progressive brain lesions.\n* Poor bone marrow reserve resulting in low blood cell count.\n* Poor liver and kidney functions, abnormal coagulation tests.\n* Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments.\n* Maintenance therapy with prednisolone >7.5 mg/day orally or equivalent during the study.\n* Non-resolution of any prior treatment related toxicity to Grade <2, except alopecia, vitiligo, fatigue and hypothyroidism controlled with replacement therapies.\n* Moderate to severe immune related adverse event to prior immune-modulating agents within 90 days prior to the first study treatment.\n* Central nervous system lymphoma.\n* Prior allogeneic hematopoietic stem cell transplantation (HSCT) for patients with lymphoma.\n* Autologous HSCT less than 90 days prior to initiation of study intervention.\n\nThe above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial."
    },
    "inclusion_lines": [
        {
            "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": [],
    "miscellaneous_lines": [
        {
            "line": "* At least 18 years of age",
            "criterions": [
                {
                    "exact_snippets": "At least 18 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Advanced solid tumors including lymphomas for which no standard alternative therapy is available (escalation phase).",
            "criterions": [
                {
                    "exact_snippets": "Advanced solid tumors including lymphomas",
                    "criterion": "tumor type",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "advanced solid tumors",
                                "lymphomas"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "no standard alternative therapy is available",
                    "criterion": "standard alternative therapy",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Advanced melanoma (Stage IIIB-C or Stage IV, anti-PD-1/PD-L1 treated or not) or anti-PD-1/PD-L1 not treated advanced Head and Neck Squamous Cell Cancer or anti-PD-1/PD-L1 not treated Advanced Cutaneous Squamous Cell Cancer where no other alternative treatment option exists (expansion phases).",
            "criterions": [
                {
                    "exact_snippets": "Advanced melanoma (Stage IIIB-C or Stage IV",
                    "criterion": "melanoma stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "IIIB-C",
                                "IV"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "anti-PD-1/PD-L1 treated or not",
                    "criterion": "anti-PD-1/PD-L1 treatment for melanoma",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "treated or not"
                        }
                    ]
                },
                {
                    "exact_snippets": "anti-PD-1/PD-L1 not treated advanced Head and Neck Squamous Cell Cancer",
                    "criterion": "anti-PD-1/PD-L1 treatment for Head and Neck Squamous Cell Cancer",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "not treated"
                        }
                    ]
                },
                {
                    "exact_snippets": "anti-PD-1/PD-L1 not treated Advanced Cutaneous Squamous Cell Cancer",
                    "criterion": "anti-PD-1/PD-L1 treatment for Advanced Cutaneous Squamous Cell Cancer",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "not treated"
                        }
                    ]
                },
                {
                    "exact_snippets": "where no other alternative treatment option exists",
                    "criterion": "alternative treatment options",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Minimum 3 lesions enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Minimum 3 lesions",
                    "criterion": "lesions",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Injectable disease (i.e., suitable for direct intratumoral injection based on the dose level volume of each cohort and cumulative lesion size; according to the investigator's judgement).",
            "criterions": [
                {
                    "exact_snippets": "Injectable disease (i.e., suitable for direct intratumoral injection ... according to the investigator's judgement)",
                    "criterion": "injectable disease",
                    "requirements": [
                        {
                            "requirement_type": "suitability for direct intratumoral injection",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "based on the dose level volume of each cohort",
                    "criterion": "dose level volume",
                    "requirements": [
                        {
                            "requirement_type": "suitability for direct intratumoral injection",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "cumulative lesion size",
                    "criterion": "cumulative lesion size",
                    "requirements": [
                        {
                            "requirement_type": "suitability for direct intratumoral injection",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* A lesion amenable for additional tumor biopsy.",
            "criterions": [
                {
                    "exact_snippets": "A lesion amenable for additional tumor biopsy.",
                    "criterion": "lesion",
                    "requirements": [
                        {
                            "requirement_type": "amenability for biopsy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.",
            "criterions": [
                {
                    "exact_snippets": "measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria",
                    "criterion": "measurable disease",
                    "requirements": [
                        {
                            "requirement_type": "evaluation criteria",
                            "expected_value": "RECIST 1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Life expectancy more than 3 months.",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy more than 3 months.",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Willingness to provide mandatory tumor biopsy.",
            "criterions": [
                {
                    "exact_snippets": "Willingness to provide mandatory tumor biopsy",
                    "criterion": "tumor biopsy",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Male and female patients who agree to use effective contraceptive methods.",
            "criterions": [
                {
                    "exact_snippets": "Male and female patients",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "male",
                                "female"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "agree to use effective contraceptive methods",
                    "criterion": "contraceptive use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Signed informed consent.",
            "criterions": [
                {
                    "exact_snippets": "Signed informed consent.",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) performance score >1.",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance score >1",
                    "criterion": "ECOG performance score",
                    "requirements": [
                        {
                            "requirement_type": "score",
                            "expected_value": {
                                "operator": ">",
                                "value": 1,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Significant and uncontrolled concomitant illness that would adversely affect the patient's participation in the study.",
            "criterions": [
                {
                    "exact_snippets": "Significant and uncontrolled concomitant illness",
                    "criterion": "concomitant illness",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any prior organ transplantation.",
            "criterions": [
                {
                    "exact_snippets": "Any prior organ transplantation",
                    "criterion": "organ transplantation",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History within the last 5 years of an invasive malignancy other than the one treated in this study, with the exception of resected basal or squamous-cell skin cancer or carcinoma, in situ of cervix or other local tumors considered cured by local treatment.",
            "criterions": [
                {
                    "exact_snippets": "History within the last 5 years of an invasive malignancy other than the one treated in this study",
                    "criterion": "invasive malignancy history",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "years"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "exclusion",
                            "expected_value": [
                                "the one treated in this study",
                                "resected basal or squamous-cell skin cancer",
                                "carcinoma, in situ of cervix",
                                "other local tumors considered cured by local treatment"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of unresolved viral hepatitis; systemic immune suppression including acquired immunodeficiency syndrome (AIDS) related illnesses or human immunodeficiency virus (HIV) disease requiring antiretroviral treatment.",
            "criterions": [
                {
                    "exact_snippets": "History of unresolved viral hepatitis",
                    "criterion": "viral hepatitis",
                    "requirements": [
                        {
                            "requirement_type": "resolution",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "systemic immune suppression including acquired immunodeficiency syndrome (AIDS) related illnesses",
                    "criterion": "systemic immune suppression",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "human immunodeficiency virus (HIV) disease requiring antiretroviral treatment",
                    "criterion": "HIV disease",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior splenectomy.",
            "criterions": [
                {
                    "exact_snippets": "Prior splenectomy",
                    "criterion": "splenectomy",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* New and progressive brain lesions.",
            "criterions": [
                {
                    "exact_snippets": "New and progressive brain lesions.",
                    "criterion": "brain lesions",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "new",
                                "progressive"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Poor bone marrow reserve resulting in low blood cell count.",
            "criterions": [
                {
                    "exact_snippets": "Poor bone marrow reserve",
                    "criterion": "bone marrow reserve",
                    "requirements": [
                        {
                            "requirement_type": "quality",
                            "expected_value": "poor"
                        }
                    ]
                },
                {
                    "exact_snippets": "low blood cell count",
                    "criterion": "blood cell count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": "low"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Poor liver and kidney functions, abnormal coagulation tests.",
            "criterions": [
                {
                    "exact_snippets": "Poor liver ... functions",
                    "criterion": "liver function",
                    "requirements": [
                        {
                            "requirement_type": "quality",
                            "expected_value": "poor"
                        }
                    ]
                },
                {
                    "exact_snippets": "Poor ... kidney functions",
                    "criterion": "kidney function",
                    "requirements": [
                        {
                            "requirement_type": "quality",
                            "expected_value": "poor"
                        }
                    ]
                },
                {
                    "exact_snippets": "abnormal coagulation tests",
                    "criterion": "coagulation tests",
                    "requirements": [
                        {
                            "requirement_type": "quality",
                            "expected_value": "abnormal"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments.",
            "criterions": [
                {
                    "exact_snippets": "Ongoing or recent (within 5 years) evidence of significant autoimmune disease",
                    "criterion": "autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "recency",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "autoimmune disease that required treatment with systemic immunosuppressive treatments",
                    "criterion": "treatment with systemic immunosuppressive treatments",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Maintenance therapy with prednisolone >7.5 mg/day orally or equivalent during the study.",
            "criterions": [
                {
                    "exact_snippets": "Maintenance therapy with prednisolone >7.5 mg/day orally or equivalent",
                    "criterion": "prednisolone dosage",
                    "requirements": [
                        {
                            "requirement_type": "dosage",
                            "expected_value": {
                                "operator": ">",
                                "value": 7.5,
                                "unit": "mg/day"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Non-resolution of any prior treatment related toxicity to Grade <2, except alopecia, vitiligo, fatigue and hypothyroidism controlled with replacement therapies.",
            "criterions": [
                {
                    "exact_snippets": "Non-resolution of any prior treatment related toxicity to Grade <2",
                    "criterion": "prior treatment related toxicity",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<",
                                "value": 2,
                                "unit": "Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except alopecia",
                    "criterion": "alopecia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except ... vitiligo",
                    "criterion": "vitiligo",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except ... fatigue",
                    "criterion": "fatigue",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except ... hypothyroidism controlled with replacement therapies",
                    "criterion": "hypothyroidism",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "controlled with replacement therapies"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Moderate to severe immune related adverse event to prior immune-modulating agents within 90 days prior to the first study treatment.",
            "criterions": [
                {
                    "exact_snippets": "Moderate to severe immune related adverse event",
                    "criterion": "immune related adverse event",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "moderate",
                                "severe"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "prior immune-modulating agents",
                    "criterion": "prior immune-modulating agents",
                    "requirements": [
                        {
                            "requirement_type": "exposure",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "within 90 days prior to the first study treatment",
                    "criterion": "time since last immune-modulating agent",
                    "requirements": [
                        {
                            "requirement_type": "time",
                            "expected_value": {
                                "operator": "<=",
                                "value": 90,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Central nervous system lymphoma.",
            "criterions": [
                {
                    "exact_snippets": "Central nervous system lymphoma",
                    "criterion": "central nervous system lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior allogeneic hematopoietic stem cell transplantation (HSCT) for patients with lymphoma.",
            "criterions": [
                {
                    "exact_snippets": "Prior allogeneic hematopoietic stem cell transplantation (HSCT)",
                    "criterion": "allogeneic hematopoietic stem cell transplantation (HSCT)",
                    "requirements": [
                        {
                            "requirement_type": "prior occurrence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with lymphoma",
                    "criterion": "lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Autologous HSCT less than 90 days prior to initiation of study intervention.",
            "criterions": [
                {
                    "exact_snippets": "Autologous HSCT less than 90 days prior to initiation of study intervention.",
                    "criterion": "autologous HSCT",
                    "requirements": [
                        {
                            "requirement_type": "time since procedure",
                            "expected_value": {
                                "operator": "<",
                                "value": 90,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": [
        {
            "line": "Inclusion criteria:",
            "criterions": []
        },
        {
            "line": "Exclusion criteria:",
            "criterions": []
        },
        {
            "line": "The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.",
            "criterions": []
        }
    ]
}