Clinical Trials /

Dose Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of GSK2849330 in Subjects With Advanced Her3-Positive Solid Tumors

NCT01966445

Description:

Human Epidermal Growth Factor Receptor 3 (HER3) expression is seen across a wide variety of solid malignancies and is associated with poor prognosis. Up-regulation of HER3 expression and activity is also associated with resistance to multiple pathway inhibitors. GSK2849330, a monoclonal antibody targeting HER3, is a new agent for subjects whose tumors express HER3. This study is a phase I, first time in human, open-label, dose escalation study. The purpose of this study is to investigate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of GSK2849330 in subjects with advanced HER3-positive solid tumors. The study will be conducted in two parts. Part 1 (Dose-Escalation Phase) will include dose escalation and PK/PD cohorts to evaluate safety, PK, and PD to guide selection of dose regimen(s) for Part 2. In Part 2 (Expansion Cohorts), up to 3 cohorts will be enrolled at the dose regimen(s) selected based on Part 1 data, to evaluate safety in a larger cohort of subjects at the recommended dose regimen and also to evaluate preliminary evidence of clinical benefit.

Related Conditions:
  • Bladder Carcinoma
  • Breast Carcinoma
  • Cervical Carcinoma
  • Colorectal Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Prostate Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Dose Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of GSK2849330 in Subjects With Advanced Her3-Positive Solid Tumors
  • Official Title: A Phase I, First Time in Human, Open-Label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of Anti-Her3 Monoclonal Antibody GSK2849330 in Subjects With Advanced Her3-Positive Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 117158
  • NCT ID: NCT01966445

Conditions

  • Cancer

Interventions

DrugSynonymsArms
GSK2849330GSK2849330 Part 2

Purpose

Human Epidermal Growth Factor Receptor 3 (HER3) expression is seen across a wide variety of solid malignancies and is associated with poor prognosis. Up-regulation of HER3 expression and activity is also associated with resistance to multiple pathway inhibitors. GSK2849330, a monoclonal antibody targeting HER3, is a new agent for subjects whose tumors express HER3. This study is a phase I, first time in human, open-label, dose escalation study. The purpose of this study is to investigate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of GSK2849330 in subjects with advanced HER3-positive solid tumors. The study will be conducted in two parts. Part 1 (Dose-Escalation Phase) will include dose escalation and PK/PD cohorts to evaluate safety, PK, and PD to guide selection of dose regimen(s) for Part 2. In Part 2 (Expansion Cohorts), up to 3 cohorts will be enrolled at the dose regimen(s) selected based on Part 1 data, to evaluate safety in a larger cohort of subjects at the recommended dose regimen and also to evaluate preliminary evidence of clinical benefit.

Trial Arms

NameTypeDescriptionInterventions
GSK2849330 Part 1Experimental1 hour infusion administered intravenously at intervals of one week or more (escalating doses).
    GSK2849330 Part 2ExperimentalIntravenous infusion administered at the dose and schedule established in Part 1

      Eligibility Criteria

              Inclusion Criteria:
      
                -  Males and females >=18 years of age (at the time consent is obtained).
      
                -  Written informed consent provided.
      
                -  Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group
                   (ECOG) scale.
      
                -  Sufficient archival tumor specimen is available for HER3 immunohistochemistry (IHC)
                   analysis, or subject is willing to undergo a fresh tumor biopsy for HER3 IHC analysis.
      
                -  Histologically or cytologically confirmed diagnosis of one of the following solid
                   tumor malignancies for which no standard therapeutic alternatives exist: bladder
                   cancer, breast cancer, castrate-resistant prostate cancer, cervical cancer, colorectal
                   cancer (CRC), gastric cancer, hepatocellular carcinoma (HCC), melanoma, non-small cell
                   lung cancer (NSCLC), ovarian cancer, pancreatic cancer, squamous cancers of the head
                   and neck region (including parotid and nasopharynx).
      
              Exclusion Criteria:
      
                -  Subjects with leptomeningeal or brain metastases or spinal cord compression.
      
                -  Prior HER3- directed treatment (HER2- or EGFR-directed treatment is acceptable).
      
                -  Concurrent medical condition that would jeopardize compliance.
      
                -  Receiving chronic immunosuppressive therapies (includes daily steroid doses in excess
                   of 20 milligrams [mg]/day of prednisone).
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Number of subjects with adverse events (AEs) and serious adverse events (SAEs)
      Time Frame:Part 1 and Part 2: From Day 1 up to 45 days or 5 half lives (whichever is longer) after last dose of study treatment
      Safety Issue:
      Description:SAEs assessed as related to study participation , study treatment or GSK concomitant medication must be recorded from the time a subject consents to participate in the study up to and including any follow-up contact

      Secondary Outcome Measures

      Measure:PK parameter values for GSK2849330
      Time Frame:Part 1 and Part 2: Scheduled timepoints from Day 1 until 45 days or 5 half lives (whichever is longer) after last dose of study treatment
      Safety Issue:
      Description:
      Measure:Total and phospho-HER3 from tumor tissue
      Time Frame:Part 1 and Part 2: Screening (pre-treatment) and either Day 15 or Day 22 depending on dosing schedule
      Safety Issue:
      Description:Tumor biopsies will be obtained and analyzed for total and phospho-HER3
      Measure:Antibodies to GSK2849330 assessed in serum
      Time Frame:Part 1 and Part 2: Scheduled timepoints from Day 1 until 45 days or 5 half lives (whichever is longer) after last dose of study treatment
      Safety Issue:
      Description:
      Measure:Overall response rate
      Time Frame:Part 2: Screening and Every 8 or 9 weeks from the first dose
      Safety Issue:
      Description:Response evaluations (either complete response [CR] or partial response [PR]) will be determined according to the definitions established in the Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
      Measure:Tumor markers
      Time Frame:Part 2: Day 1 and Every 8 or 9 weeks from the first dose.
      Safety Issue:
      Description:Tumor markers will be collected as applicable to the subject's primary tumor type

      Details

      Phase:Phase 1
      Primary Purpose:Interventional
      Overall Status:Completed
      Lead Sponsor:GlaxoSmithKline

      Trial Keywords

      • GSK2849330
      • Oncology
      • First Time in Human
      • HER3

      Last Updated

      October 17, 2017