Dose Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of GSK2849330 in Subjects With Advanced Her3-Positive Solid Tumors
Condition: Cancer; Neoplasms
Intervention: GSK2849330
Intervention description: Solution containing 100 mg/millilter (mL) GSK2849330 for intravenous infusion
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: GSK2849330; Oncology; First Time in Human; HER3

Summary:

      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.
    

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).