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CancerPhase 1NCT02345174

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

A Phase 1 study testing GSK2849330 and 89Zr-GSK2849330 in people with Cancer and Neoplasms, run by GlaxoSmithKline at 2 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cancer, Neoplasms
What is being tested?
GSK2849330 and 89Zr-GSK2849330
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
2 sitesNetherlands
Study dates
19 Mar 2015to 2 Jun 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).

Who cannot join

  • 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 locations and contacts

2 sites in 1 country.

Netherlands2 sites

  • GSK Investigational Site

    Amsterdam, 1081 HV

  • GSK Investigational Site

    Amsterdam, 1081 H

Other trials in Netherlands

About this study

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

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.

Conditions
Cancer, Neoplasms
Being tested
GSK2849330, 89Zr-GSK2849330
Keywords
zirconium, oncology, mAb, receptor occupancy, dose, PET, HER3, 89-Zr, biodistribution, tumours
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK2849330Drug

    GSK2849330 solution (100 mg/mL) for infusion diluted in 0.9% sodium chloride to the appropriate concentration for the dose.

  • 89Zr-GSK2849330Drug

    89Zr-GSK2849330 solution for intravenous administration diluted with GSK2849330 Solution for Infusion (unlabelled GSK2849330) with a target radioactivity of 37MBq and a total antibody concentration of 0.4 mg/mL or 1.2 mg/mL.

Study groups in NCT02345174
Study groupRoleWhat they receive
Imaging Phase + Continuation PhaseExperimentalIn Part 1 of the study, participants will receive a dose of 89Zr-GSK2849330 (Dose 1), with an activity of no more than 37 MegaBequerel (MBq) and a variable total dose of GSK2849330. PET scans will be acquired within 7 days. Two weeks after Dose 1 participants will receive second dose of 89Zr-GSK2849330 (Dose 2) and a variable total dose of GSK2849330. Participants will continue to receive unlabelled GSK2849330 (in Part 2) either at established dose level or as decided by medical monitor.
Receives: Drug: GSK2849330; Drug: 89Zr-GSK2849330

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Standardized Uptake Value (SUV).

    Regions of interest (RoI) will be outlined from PET-CT images to represent the tissue radioactivity concentration through the values of SUVmean and SUVpeak.

    Measured: Up to Day 21

  2. Volume of region of interest.

    RoIs will be outlined to represent whole organs and include the volumes encircled

    Measured: Up to Day 21

Secondary outcomes (13)

  1. Anatomical localization of radiolabel.

    Anatomical localization of radiolabel will be evaluated to establish dose-dependency of inhibition of target mediated uptake of 89Zr-GSK2849330 by unlabeled GSK2849330.

    Measured: Up to Day 21

  2. Uptake of-GSK2849330 in tumors using pharmacometric model

    Uptake of GSK2849330 in tumors will be estimated to establish dose-dependency of inhibition of target mediated uptake of 89Zr-GSK2849330 by unlabeled GSK2849330.

    Measured: Up to Day 21

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

    Change in uptake parameters following dose 1 and 2 will estimated to establish dose-dependency of inhibition of target mediated uptake of 89Zr-GSK2849330 by unlabeled GSK2849330.

    Measured: Up to Day 21

  4. Average radioactivity concentration in whole blood and plasma

    Average radioactivity concentration will be determined and expressed as SUV and is equal to tissue radioactivity concentration normalized by administered amount of radioactivity per body weight.

    Measured: Up to Day 21

  5. Tumor features assessment

    Features of tumor will include central necrosis, irregular shape, non-uniform uptake and lesion ID

    Measured: Up to Day 21

  6. Composite of pharmacokinetic (PK) parameters of GSK2849330

    Measurements will include: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve (AUC(0-t), AUC(0-Tau) (repeat dosing) and/or AUC(0-Infinity) (single dose), apparent terminal phase elimination rate constant (lambda z) and apparent terminal phase half-life (t½)

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

  7. Organ dose measured in milliSievert (mSv) for each organ

    Measured: Up to Day 21

  8. Effective dose value measured in mSv

    Measured: Up to Day 21

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

    AEs and SAEs will be collected from the time the first dose of study treatment is administered until 45 days following discontinuation of study treatment

    Measured: Average of 6 months

  10. Change from baseline in laboratory parameters

    Clinical laboratory tests will include clinical chemistry, routine urinalysis, haematology laboratory evaluations and additional parameters

    Measured: Baseline and up to 6 months

  11. Left ventricular ejection fraction (LVEF) assessment

    LVEF will be assessed as a measure of safety and tolerability measured by echocardiography (ECHO) or multi gated acquisition (MUGA) scans

    Measured: Average of 6 months

  12. Vital signs monitoring.

    Vital sign measurements will include systolic and diastolic blood pressure (BP), temperature, and pulse rate

    Measured: Average of 6 months

  13. Serum titer of the anti-GSK2849330 antibodies.

    Samples will be analyzed for the presence of anti-GSK2849330 antibodies using a validated immunoelectrochemiluminescent (ECL) assay.

    Measured: Average of 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jan 2015 (estimated)
  2. Study start19 Mar 2015
  3. Primary completion2 Jun 2016
  4. Study completion2 Jun 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02345174
Sponsor's protocol ID
200980
Status last verified
Feb 2019
First submitted
19 Jan 2015
Last updated
21 Feb 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Publications

  • Menke-van der Houven van Oordt CW, McGeoch A, Bergstrom M, McSherry I, Smith DA, Cleveland M, Al-Azzam W, Chen L, Verheul H, Hoekstra OS, Vugts DJ, Freedman I, Huisman M, Matheny C, van Dongen G, Zhang S. Immuno-PET Imaging to Assess Target Engagement: Experience from 89Zr-Anti-HER3 mAb (GSK2849330) in Patients with Solid Tumors. J Nucl Med. 2019 Jul;60(7):902-909. doi: 10.2967/jnumed.118.214726. Epub 2019 Feb 7.

    PubMed 30733323

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK2849330 and 89Zr-GSK2849330 in people with Cancer and Neoplasms, run by GlaxoSmithKline at 2 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Standardized Uptake Value (SUV). (time frame: Up to Day 21). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02345174, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2019.

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