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.
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
Interventions
| Drug | Synonyms | Arms |
|---|
| GSK2849330 | | GSK2849330 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
| Name | Type | Description | Interventions |
|---|
| GSK2849330 Part 1 | Experimental | 1 hour infusion administered intravenously at intervals of one week or more (escalating doses). | |
| GSK2849330 Part 2 | Experimental | Intravenous 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
