Last updated: 09/06/2021 12:40:10

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

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GSK study ID
117158
See study documents
Clinicaltrials.gov ID
NCT01966445
See results summary
EudraCT ID
2013-001699-39
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

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 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:

Number of participants with adverse events (AEs) and serious adverse events (SAEs)-Parts 1 and 2

Timeframe: Median of 6.143 weeks of drug exposure

Number of participants with dose-limiting toxicities (DLTs)-Parts 1 and 2

Timeframe: Up to 28 days

Number of participants with grade change from Baseline in clinical chemistry data-Parts 1 and 2

Timeframe: Baseline and median of 6.143 weeks of drug exposure

Number of participants with change from Baseline in clinical chemistry data with respect to normal range-Parts 1 and 2

Timeframe: Baseline and median of 6.143 weeks of drug exposure

Number of participants with grade change from Baseline in hematology data-Parts 1 and 2

Timeframe: Baseline and median of 6.143 weeks of drug exposure

Number of participants with change from Baseline in hematology data with respect to normal range-Parts 1 and 2

Timeframe: Baseline and median of 6.143 weeks of drug exposure

Number of participants with change from Baseline in urinalysis data with respect to normal range-Parts 1 and 2

Timeframe: Baseline and median of 6.143 weeks of drug exposure

Number of participants with change from Baseline in vital signs-Parts 1 and 2

Timeframe: Baseline and median of 6.143 weeks of drug exposure

Number of participants with abnormal electrocardiogram (ECG) findings-Parts 1 and 2

Timeframe: Median of 6.143 weeks of drug exposure

Secondary outcomes:

Maximum observed plasma concentration (Cmax) of GSK2849330-Part 1

Timeframe: Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose

Cmax of GSK2849330-Part 2

Timeframe: Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose

Time of occurrence of Cmax (Tmax) for GSK2849330-Part 1

Timeframe: Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose

Tmax for GSK2849330-Part 2

Timeframe: Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose

Area under the concentration time curve (AUC) to a fixed nominal time (AUC[0 to 168]) and AUC(0 to 336) for GSK2849330-Part 1

Timeframe: Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose

AUC(0 to 168) and AUC(0 to 336) for GSK2849330-Part 2

Timeframe: Day 1 (pre-dose, 1 and 6 hours post-dose), Day 8, Day 15, Day 29, and every 12 weeks from first dose

Serum HER3 from tumor tissue-Parts 1 and 2

Timeframe: Median of 6.143 weeks of drug exposure

Overall response rate (ORR)-Parts 1 and 2

Timeframe: Median of 6.143 weeks of drug exposure

Number of participants with antibodies to GSK2849330 in serum

Timeframe: Median of 6.143 weeks of drug exposure

Percentage of cluster of differentiation (CD) marker

Timeframe: Median of 6.143 weeks of drug exposure

Interventions:
  • Biological/vaccine: GSK2849330
    • Enrollment:
    29
    Primary completion date:
    2017-18-09
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Cancer, Neoplasms
    Product
    GSK2849330
    Collaborators
    Not applicable
    Study date(s)
    November 2013 to September 2017
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    No
    • Males and females >=18 years of age (at the time consent is obtained).
    • Written informed consent provided.
    • Subjects with leptomeningeal or brain metastases or spinal cord compression.
    • Prior HER3- directed treatment (HER2- or EGFR-directed treatment is acceptable).
    Inclusion and exclusion 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).

    Trial location(s)

    Location
    Status
    Contact us
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    Location
    GSK Investigational Site
    Amsterdam, Netherlands, 1066 CX
    Status
    Study Complete
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    Location
    GSK Investigational Site
    GRONINGEN, Netherlands, 9713 GZ
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Heidelberg, Victoria, Australia, 3084
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Melbourne, Victoria, Australia, 3004
    Status
    Study Complete
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    Location
    GSK Investigational Site
    NIJMEGEN, Netherlands, 6525 GA
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Nedlands, Western Australia, Australia, 6009
    Status
    Study Complete
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    Showing 1 - 6 of 9 Results

    Study documents

    Clinical study report
    Available language(s): English
    Download document(s)
    Protocol
    Available language(s): English
    Download document(s)
    Statistical analysis plan
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2017-18-09
    Actual study completion date
    2017-18-09

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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