Neratinib and Capmatinib Combination (Phase Ib/II) in Metastatic Breast Cancer and Inflammatory Breast Cancer Patients With Abnormal HER-family and c-Met Pathway Activity as Measured by the CELsignia Signaling Analysis Test

[
  {
    "op": "replace",
    "path": "/protocolSection/statusModule/statusVerifiedDate",
    "value": "2025-03"
  },
  {
    "op": "replace",
    "path": "/protocolSection/statusModule/lastUpdateSubmitDate",
    "value": "2025-03-24"
  },
  {
    "op": "replace",
    "path": "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
    "value": "2025-04-09"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/primaryOutcomes/1/measure",
    "value": "To Determine Overall Response Rate"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/primaryOutcomes/1/description",
    "value": "The overall response rate (ORR) for patients treated at the MTD in Phase II was assessed.\nORR was defined as the proportion of patients who achieved a partial response or complete response as their best response.\nAll tumor responses were evaluated according to RECIST 1.1 criteria and measured using the QIAC system."
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/0/description",
    "value": "Adverse events (AEs) graded using CTCAE version 5.0: ≥ Grade 2 for non-hematological and ≥ Grade 3 for hematological AEs observed after the first protocol intervention."
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/1/description",
    "value": "Clinical benefit rate (CBR) is defined as the proportion of patients achieving complete response, partial response, or stable disease for ≥24 weeks, was summarized by frequency and percentage with Wilson 95% confidence intervals, overall and by dose level."
  },
  {
    "op": "replace",
    "path": "/resultsSection/baselineCharacteristicsModule/measures/0/classes/0/categories/0/measurements/2/lowerLimit",
    "value": "34"
  },
  {
    "op": "remove",
    "path": "/resultsSection/baselineCharacteristicsModule/measures/0/reviewUnit"
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/1/title",
    "value": "To Determine Overall Response Rate"
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/1/description",
    "value": "The overall response rate (ORR) for patients treated at the MTD in Phase II was assessed.\nORR was defined as the proportion of patients who achieved a partial response or complete response as their best response.\nAll tumor responses were evaluated according to RECIST 1.1 criteria and measured using the QIAC system."
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/1/populationDescription",
    "value": "Patients treated at the MTD in Phase II."
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/2/description",
    "value": "Adverse events (AEs) graded using CTCAE version 5.0: ≥ Grade 2 for non-hematological and ≥ Grade 3 for hematological AEs observed after the first protocol intervention."
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/2/populationDescription",
    "value": "Patients treated at the MTD in Phase II."
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/description",
    "value": "Clinical benefit rate (CBR) is defined as the proportion of patients achieving complete response, partial response, or stable disease for ≥24 weeks, was summarized by frequency and percentage with Wilson 95% confidence intervals, overall and by dose level."
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/populationDescription",
    "value": "The baseline analysis population included all treated participants.\nHowever, patients who discontinued the study due to toxicities before completing Cycle 2 and without a RECIST assessment after therapy were excluded."
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/groups/0/title",
    "value": "Phase Ib: Dose Level 1"
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/groups/0/description",
    "value": "Neratinib 120 mg Dose 1-7, 160 mg through end of treatment once daily + Capmatinib 400 mg twice daily"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/groups/1",
    "value": {
      "id": "OG001",
      "title": "Phase Ib: Dose Level 2",
      "description": "Neratinib 120 mg Dose 1-7,160 mg Dose 8-14, 200 mg through end of treatment once daily + Capmatinib 400 mg twice daily"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/groups/2",
    "value": {
      "id": "OG002",
      "title": "Phase Ib: Dose Level 3",
      "description": "Neratinib 120 mg Dose 1-7, 160 mg Dose 8-14, 240 mg through end of treatment once daily + Capmatinib 400 mg twice daily"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/groups/3",
    "value": {
      "id": "OG003",
      "title": "Phase Ib: Dose Level-1",
      "description": "Neratinib 120 mg Dose 1-7, 160 mg through end of treatment once daily + Capmatinib 300 mg twice daily"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/groups/4",
    "value": {
      "id": "OG004",
      "title": "Phase Ib: Dose Level-2",
      "description": "Neratinib 120 mg through end of treatment once daily + Capmatinib 200 mg twice daily"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/groups/5",
    "value": {
      "id": "OG005",
      "title": "Phase II",
      "description": "Subjects receive neratinib and capmatinib.\nThe MTD determined during Phase Ib will be used."
    }
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/denoms/0/counts/0/value",
    "value": "5"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/denoms/0/counts/1",
    "value": {
      "value": "0",
      "groupId": "OG001"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/denoms/0/counts/2",
    "value": {
      "value": "0",
      "groupId": "OG002"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/denoms/0/counts/3",
    "value": {
      "value": "2",
      "groupId": "OG003"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/denoms/0/counts/4",
    "value": {
      "value": "0",
      "groupId": "OG004"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/denoms/0/counts/5",
    "value": {
      "value": "0",
      "groupId": "OG005"
    }
  },
  {
    "op": "remove",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/measureCategoriesReviewUnit"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/paramType",
    "value": "NUMBER"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/dispersionType",
    "value": "95% Confidence Interval"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/unitOfMeasure",
    "value": "percentage"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/3/classes",
    "value": [
      {
        "categories": [
          {
            "measurements": [
              {
                "value": "20.0",
                "groupId": "OG000",
                "lowerLimit": "3.6",
                "upperLimit": "62.4"
              },
              {
                "value": "0.0",
                "groupId": "OG003",
                "lowerLimit": "0.0",
                "upperLimit": "65.8"
              }
            ]
          }
        ]
      }
    ]
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/populationDescription",
    "value": "Baseline analysis population included all participants treated."
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/groups/0/title",
    "value": "Phase Ib: Dose Level 1"
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/groups/0/description",
    "value": "Neratinib 120 mg Dose 1-7, 160 mg through end of treatment once daily + Capmatinib 400 mg twice daily"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/groups/1",
    "value": {
      "id": "OG001",
      "title": "Phase Ib: Dose Level 2",
      "description": "Neratinib 120 mg Dose 1-7,160 mg Dose 8-14, 200 mg through end of treatment once daily + Capmatinib 400 mg twice daily"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/groups/2",
    "value": {
      "id": "OG002",
      "title": "Phase Ib: Dose Level 3",
      "description": "Neratinib 120 mg Dose 1-7, 160 mg Dose 8-14, 240 mg through end of treatment once daily + Capmatinib 400 mg twice daily"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/groups/3",
    "value": {
      "id": "OG003",
      "title": "Phase Ib: Dose Level-1",
      "description": "Neratinib 120 mg Dose 1-7, 160 mg through end of treatment once daily + Capmatinib 300 mg twice daily"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/groups/4",
    "value": {
      "id": "OG004",
      "title": "Phase Ib: Dose Level-2",
      "description": "Neratinib 120 mg through end of treatment once daily + Capmatinib 200 mg twice daily"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/groups/5",
    "value": {
      "id": "OG005",
      "title": "Phase II",
      "description": "Subjects receive neratinib and capmatinib.\nThe MTD determined during Phase Ib will be used."
    }
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/denoms/0/counts/0/value",
    "value": "7"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/denoms/0/counts/1",
    "value": {
      "value": "0",
      "groupId": "OG001"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/denoms/0/counts/2",
    "value": {
      "value": "0",
      "groupId": "OG002"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/denoms/0/counts/3",
    "value": {
      "value": "3",
      "groupId": "OG003"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/denoms/0/counts/4",
    "value": {
      "value": "0",
      "groupId": "OG004"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/denoms/0/counts/5",
    "value": {
      "value": "0",
      "groupId": "OG005"
    }
  },
  {
    "op": "remove",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/measureCategoriesReviewUnit"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/paramType",
    "value": "NUMBER"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/unitOfMeasure",
    "value": "Months"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4/classes",
    "value": [
      {
        "categories": [
          {
            "measurements": [
              {
                "value": "NA",
                "comment": "No patient experienced partial response nor complete response, so duration of response is not estimable.",
                "groupId": "OG000"
              },
              {
                "value": "NA",
                "comment": "No patient experienced partial response nor complete response, so duration of response is not estimable.",
                "groupId": "OG003"
              }
            ]
          }
        ]
      }
    ]
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5/populationDescription",
    "value": "Baseline analysis population included all participants treated."
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5/groups/0/title",
    "value": "Phase Ib: Dose Level 1"
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5/groups/0/description",
    "value": "Neratinib 120 mg Dose 1-7, 160 mg through end of treatment once daily + Capmatinib 400 mg twice daily"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5/groups/1",
    "value": {
      "id": "OG001",
      "title": "Phase Ib: Dose Level 2",
      "description": "Neratinib 120 mg Dose 1-7, 160 mg Dose 8-14, 200 mg through end of treatment once daily + Capmatinib 400 mg twice daily"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5/groups/2",
    "value": {
      "id": "OG002",
      "title": "Phase Ib: Dose Level 3",
      "description": "Neratinib 120 mg Dose 1-7, 160 mg Dose 8-14, 240 mg through end of treatment once daily + Capmatinib 400 mg twice daily"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5/groups/3",
    "value": {
      "id": "OG003",
      "title": "Phase Ib: Dose Level-2",
      "description": "Neratinib 120 mg through end of treatment once daily + Capmatinib 200 mg twice daily"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5/groups/4",
    "value": {
      "id": "OG004",
      "title": "Phase II",
      "description": "Subjects receive neratinib and capmatinib.\nThe MTD determined during Phase Ib will be used."
    }
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5/denoms/0/counts/0/value",
    "value": "7"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5/denoms/0/counts/1",
    "value": {
      "value": "0",
      "groupId": "OG001"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5/denoms/0/counts/2",
    "value": {
      "value": "0",
      "groupId": "OG002"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5/denoms/0/counts/3",
    "value": {
      "value": "3",
      "groupId": "OG003"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5/denoms/0/counts/4",
    "value": {
      "value": "0",
      "groupId": "OG004"
    }
  },
  {
    "op": "remove",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5/measureCategoriesReviewUnit"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5/paramType",
    "value": "MEAN"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5/dispersionType",
    "value": "95% Confidence Interval"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5/unitOfMeasure",
    "value": "Months"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5/classes",
    "value": [
      {
        "categories": [
          {
            "measurements": [
              {
                "value": "4.76",
                "groupId": "OG000",
                "lowerLimit": "2.13",
                "upperLimit": "7.39"
              },
              {
                "value": "4.54",
                "groupId": "OG003",
                "lowerLimit": "0.70",
                "upperLimit": "8.38"
              }
            ]
          }
        ]
      }
    ]
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/populationDescription",
    "value": "All patients who received at least one dose of the study medication."
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/groups/0/title",
    "value": "Phase Ib: Dose Level 1"
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/groups/0/description",
    "value": "Neratinib 120 mg Dose 1-7, 160 mg through end of treatment once daily + Capmatinib 400 mg twice daily"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/groups/1",
    "value": {
      "id": "OG001",
      "title": "Phase Ib: Dose Level 2",
      "description": "Neratinib 120 mg Dose 1-7, 160 mg Dose 8-14, 200 mg through end of treatment once daily + Capmatinib 400 mg twice daily"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/groups/2",
    "value": {
      "id": "OG002",
      "title": "Phase Ib: Dose Level 3",
      "description": "Neratinib 120 mg Dose 1-7, 160 mg Dose 8-14, 240 mg through end of treatment once daily + Capmatinib 400 mg twice daily"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/groups/3",
    "value": {
      "id": "OG003",
      "title": "Phase Ib: Dose Level-1",
      "description": "Neratinib 120 mg Dose 1-7, 160 mg through end of treatment once daily + Capmatinib 300 mg twice daily"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/groups/4",
    "value": {
      "id": "OG004",
      "title": "Phase Ib: Dose Level-2",
      "description": "Neratinib 120 mg through end of treatment once daily + Capmatinib 200 mg twice daily"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/groups/5",
    "value": {
      "id": "OG005",
      "title": "Phase II",
      "description": "Subjects receive neratinib and capmatinib.\nThe MTD determined during Phase Ib will be used."
    }
  },
  {
    "op": "replace",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/denoms/0/counts/0/value",
    "value": "7"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/denoms/0/counts/1",
    "value": {
      "value": "0",
      "groupId": "OG001"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/denoms/0/counts/2",
    "value": {
      "value": "0",
      "groupId": "OG002"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/denoms/0/counts/3",
    "value": {
      "value": "3",
      "groupId": "OG003"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/denoms/0/counts/4",
    "value": {
      "value": "0",
      "groupId": "OG004"
    }
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/denoms/0/counts/5",
    "value": {
      "value": "0",
      "groupId": "OG005"
    }
  },
  {
    "op": "remove",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/measureCategoriesReviewUnit"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/paramType",
    "value": "NUMBER"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/unitOfMeasure",
    "value": "Percentage"
  },
  {
    "op": "add",
    "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6/classes",
    "value": [
      {
        "categories": [
          {
            "measurements": [
              {
                "value": "85.7",
                "groupId": "OG000"
              },
              {
                "value": "66.7",
                "groupId": "OG003"
              }
            ]
          }
        ]
      }
    ]
  },
  {
    "op": "replace",
    "path": "/resultsSection/adverseEventsModule/timeFrame",
    "value": "From the initiation of the first protocol-specific intervention to 2 years following the last dose of the drug."
  },
  {
    "op": "replace",
    "path": "/resultsSection/adverseEventsModule/description",
    "value": "Adverse events were evaluated based on the CTCAE version 5.0.\nAll study participants who received neratinib and capmatinib combination therapy were included in the safety analysis."
  },
  {
    "op": "add",
    "path": "/resultsSection/adverseEventsModule/allCauseMortalityReviewUnit",
    "value": {
      "resetReasons": [
        "Information in other parts of the record suggests that adverse events were collected that are not reported here."
      ]
    }
  },
  {
    "op": "replace",
    "path": "/annotationSection/annotationModule/unpostedAnnotation/unpostedEvents/0/date",
    "value": "2025-04-08"
  }
]