Dose Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of GSK2849330 in Subjects With Advanced Her3-Positive Solid Tumors
| Status: | Completed |
|---|---|
| Conditions: | Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 7/21/2018 |
| Start Date: | November 26, 2013 |
| End Date: | September 18, 2017 |
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
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.
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.
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).
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