Last updated: 07/31/2020 03:20:16

Immuno Positron Emission Tomography Study of GSK2849330 in Subjects with Human Epidermal Growth Factor Receptor 3-Positive Solid Tumors

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GSK study ID
200980
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Clinicaltrials.gov ID
NCT02345174
EudraCT ID
Not applicable
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: An Open Label Positron Emission Tomography (PET) Imaging Study Using 89Zirconium to Investigate the Biodistribution of Anti-HER3 monoclonal Antibody (mAb) GSK2849330 and Characterize its Dose-receptor Occupancy Relationship 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 (mAb) targeting HER3, is a new agent for subjects whose tumors express HER3. This study aims to characterise the biodistribution and dose-receptor occupancy relationship of GSK2849330 in patients with advanced HER3 expressing solid tumours via the use of PET imaging. This study will be conducted in two parts. Part 1 will be the imaging phase where each subject will receive two doses of GSK2849330 containing both Zirconium-89 (89Zr) labelled GSK2849330 and unlabeled GSK2849330. The amount of unlabeled GSK2849330 present in each dose will be varied to explore the effect on target mediated uptake of 89Zr into HER3 expressing tissues and tumors. Subjects will then proceed to the continuation phase (Part 2) for continued treatment with unlabelled GSK2849330. The study is planned to enroll approximately 12-15 subjects.
Primary purpose:
Other
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Not applicable
Primary outcomes:

Standardized Uptake Value (SUV).

Timeframe: Up to Day 21

Volume of region of interest.

Timeframe: Up to Day 21

Secondary outcomes:

Anatomical localization of radiolabel.

Timeframe: Up to Day 21

Uptake of-GSK2849330 in tumors using pharmacometric model

Timeframe: Up to Day 21

Change in uptake parameters in response to the dose difference between dose 1 and 2.

Timeframe: Up to Day 21

Average radioactivity concentration in whole blood and plasma

Timeframe: Up to Day 21

Tumor features assessment

Timeframe: Up to Day 21

Composite of pharmacokinetic (PK) parameters of GSK2849330

Timeframe: Predose, and at 1, 3, 6, 12 and 24 hours post dose.

Organ dose measured in milliSievert (mSv) for each organ

Timeframe: Up to Day 21

Effective dose value measured in mSv

Timeframe: Up to Day 21

Overall incidence of Adverse events (AEs) and Serious Adverse events (SAEs)

Timeframe: Average of 6 months

Change from baseline in laboratory parameters

Timeframe: Baseline and up to 6 months

Left ventricular ejection fraction (LVEF) assessment

Timeframe: Average of 6 months

Vital signs monitoring.

Timeframe: Average of 6 months

Serum titer of the anti-GSK2849330 antibodies.

Timeframe: Average of 6 months

Interventions:
  • Drug: GSK2849330
  • Drug: 89Zr-GSK2849330
    • Enrollment:
    6
    Primary completion date:
    2016-02-06
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    C. Willemien Menke-van der Houven van Oordt, Adam McGeoch, Mats Bergstrom, Iain McSherry, Deborah A Smith, Matthew Cleveland, Wasfi Al-Azzam, Liangfu Chen, Henk Verheul, Otto S Hoekstra, Danielle J. Vugts, Immanuel Freedman, Marc Huisman, Chris Matheny, Guus van Dongen, Sean Zhang. ImmunoPET imaging to assess target engagement: Experience from 89Zr-anti-HER3 mAb (GSK2849330) in patients with solid tumors. J Nucl Med. 2018;60(7):902-909 DOI: 10.2967/jnumed.118.214726 PMID: 30733323
    Medical condition
    Cancer, Neoplasms
    Product
    GSK2849330, GW589309
    Collaborators
    Not applicable
    Study date(s)
    March 2015 to June 2016
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    No
    • Inclusion Criteria
    • Males and females >=18 years of age (at the time consent is obtained).
    Inclusion and exclusion criteria
    Inclusion 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 tumor biopsy for HER3 IHC analysis.
    • Subjects must have tumours with documented HER3 expression on the cell surface (1+, 2+ or 3+) of the invasive component of tumour (either on archival tissue or a fresh biopsy) using an analytically validated IHC assay by central laboratory.
    • Histologically or cytologically confirmed diagnosis of solid tumour malignancy for which no standard therapeutic alternatives exist.
    • Adequate baseline organ functions
    • Left ventricular ejection fraction (LVEF) >=50% by Echocardiogram (ECHO) or Multi gated acquisition scan (MUGA).
    • Subjects must have at least two measurable lesions on Computed tomography (CT) or Magnetic resonance imaging (MRI) scan with a shortest axis of at least 20 millimeter (mm). Exclusion Criteria:
    • Subjects with leptomeningeal or brain metastases or spinal cord compression
    • Prior HER3- directed treatment (HER2- or EGFR-directed treatment is acceptable).
    • Unresolved toxicity greater than National Cancer Institute
    • Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.0 Grade 1 from previous anti-cancer therapy
    • Known or suspected hypersensitivity reaction to prior biologic therapy
    • Evidence of another active malignancy (excludes non-melanoma skin cancer).
    • Concurrent medical condition that would jeopardize compliance with the protocol.
    • Receiving concurrent anti-tumor therapies, or chronic immunosuppressive therapies (includes daily steroid doses in excess of 20 milligram (mg)/day of prednisolone).

    Trial location(s)

    Location
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    AMSTERDAM, Netherlands, 1081 HV
    Status
    Study Complete
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    Study documents

    Clinical study report
    Available language(s): English
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    Protocol
    Available language(s): English
    Download document(s)
    Scientific result summary
    Available language(s): English
    Download document(s)

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

    Results overview

    Refer to study documents

    Recruitment status
    Study complete
    Actual primary completion date
    2016-02-06
    Actual study completion date
    2016-02-06

    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

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    Additional information
    Results for study 200980 can be found on the GSK Clinical Study Register.
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