Overview

This trial is active, not recruiting.

Condition cancer
Treatment gsk2849330
Phase phase 1
Sponsor GlaxoSmithKline
Start date November 2013
End date September 2016
Trial size 155 participants
Trial identifier NCT01966445, 117158

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
1 hour infusion administered intravenously at intervals of one week or more (escalating doses).
gsk2849330
Solution containing 100 mg/millilter (mL) GSK2849330 for intravenous infusion
(Experimental)
Intravenous infusion administered at the dose and schedule established in Part 1
gsk2849330
Solution containing 100 mg/millilter (mL) GSK2849330 for intravenous infusion

Primary Outcomes

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
Dose-limiting toxicities (DLTs)
time frame: Part 1 and Part 2: From Day 1 up to Day 29
Change in laboratory values
time frame: Part 1 and Part 2: From Screening up to approximately 28 days after the last dose of study treatment
Change in electrocardiograms (ECGs)
time frame: Part 1 and Part 2: From Screening up to approximately 28 days after the last dose of study treatment
Changes in vital signs
time frame: Part 1 and Part 2: From Screening up to approximately 28 days after the last dose of study treatment

Secondary Outcomes

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
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
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
Overall response rate
time frame: Part 2: Screening and Every 8 or 9 weeks from the first dose
Tumor markers
time frame: Part 2: Day 1 and Every 8 or 9 weeks from the first dose.

Eligibility Criteria

Male or female participants at least 18 years old.

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).

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.