Study of the Combination of KD019 and Trastuzumab in Subjects With HER2-Positive Metastatic Breast Cancer

[
  {
    "op": "replace",
    "path": "/protocolSection/statusModule/statusVerifiedDate",
    "value": "2021-05"
  },
  {
    "op": "replace",
    "path": "/protocolSection/statusModule/whyStopped",
    "value": "Sponsor closed the study due to lack of response."
  },
  {
    "op": "replace",
    "path": "/protocolSection/statusModule/lastUpdateSubmitDate",
    "value": "2021-05-07"
  },
  {
    "op": "replace",
    "path": "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
    "value": "2021-05-12"
  },
  {
    "op": "replace",
    "path": "/protocolSection/designModule/designInfo/interventionModel",
    "value": "PARALLEL"
  },
  {
    "op": "add",
    "path": "/protocolSection/designModule/designInfo/interventionModelDescription",
    "value": "Part 1 is a phase 1b ascending dose-finding study for establishing the maximum tolerated dose (MTD) of tesevatinib (with trastuzumab).\nPart 2 is a phase 2a expansion study with subjects assigned to 1 of 3 parallel groups who were administered the MTD of tesevatinib (with trastuzumab)."
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/primaryOutcomes/0/measure",
    "value": "Safety: Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability and MTD"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/0/measure",
    "value": "Efficacy: Response Rate"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/1/measure",
    "value": "Efficacy: Median Progression-Free Survival"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/1/description",
    "value": "To determine the median progression-free survival (PFS) and the percentage of subjects without disease progression after 2, 4, and 6 months of dosing."
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/2/measure",
    "value": "Efficacy: Median Overall Survival"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/2/description",
    "value": "To determine the median overall survival (OS)."
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame",
    "value": "30 months"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/3/measure",
    "value": "Pharmacokinetics: Cmax"
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/3/description",
    "value": "To evaluate the following pharmacokinetic parameter maximum concentration (Cmax) for the combination of tesevatinib and trastuzumab.\nPlasma concentrations of tesevatinib and serum concentrations of trastuzumab will be summarized by dose, sample collection day, and sample collection time for each drug."
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame",
    "value": "27 months"
  },
  {
    "op": "add",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/4",
    "value": {
      "measure": "Pharmacokinetics: Tmax",
      "timeFrame": "27 months",
      "description": "To evaluate the following PK parameter time of maximum concentration (Tmax) for the combination of tesevatinib and trastuzumab.\nPlasma concentrations of tesevatinib and serum concentrations of trastuzumab will be summarized by dose, sample collection day, and sample collection time for each drug."
    }
  },
  {
    "op": "add",
    "path": "/protocolSection/outcomesModule/secondaryOutcomes/5",
    "value": {
      "measure": "Pharmacokinetics: AUC(0-24)",
      "timeFrame": "27 months",
      "description": "To evaluate the following PK parameter area under concentration curve from 0 to 24 hours (AUC[0-24hr]) for the combination of tesevatinib and trastuzumab.\nPlasma concentrations of tesevatinib and serum concentrations of trastuzumab will be summarized by dose, sample collection day, and sample collection time for each drug."
    }
  },
  {
    "op": "replace",
    "path": "/protocolSection/outcomesModule/otherOutcomes/0/description",
    "value": "Efficacy: To evaluate changes in neurologic symptoms in subjects with leptomeningeal metastases.\nThis outcome measure is specific to subjects with leptomeningeal metastases (Phase 2a, Group 3)."
  },
  {
    "op": "remove",
    "path": "/protocolSection/outcomesModule/otherOutcomes/1"
  },
  {
    "op": "add",
    "path": "/annotationSection",
    "value": {
      "annotationModule": {
        "unpostedAnnotation": {
          "unpostedEvents": [
            {
              "date": "2022-01-04",
              "type": "RELEASE"
            },
            {
              "date": "2022-02-01",
              "type": "RESET"
            }
          ],
          "unpostedResponsibleParty": "Kadmon Corporation, LLC"
        }
      }
    }
  }
]