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

NCT02345174 | Completed Phase 1

• 1 other identifier: 200980
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief 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 (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

Keywords

zirconium; oncology; mAb; receptor occupancy; dose; PET; HER3; 89-Zr; biodistribution; tumours

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to Day 21

• Volume of region of interest.

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

  Up to Day 21

Secondary Outcomes (13)

• Anatomical localization of radiolabel.

  Up to Day 21

• Uptake of-GSK2849330 in tumors using pharmacometric model

  Up to Day 21

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

  Up to Day 21

• Average radioactivity concentration in whole blood and plasma

  Up to Day 21

• Tumor features assessment

  Up to Day 21

Study Arms (1)

Imaging Phase + Continuation Phase

EXPERIMENTAL

In 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.

Drug: GSK2849330; Drug: 89Zr-GSK2849330

Interventions

GSK2849330 DRUG

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

Imaging Phase + Continuation Phase

89Zr-GSK2849330 DRUG

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.

Imaging Phase + Continuation Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Amsterdam, 1081 HV, Netherlands

Location

GSK Investigational Site

Amsterdam, 1081 H, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 30733323 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Neoplasms

Interventions

GSK2849330

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

• GSK Clinical Trials

  GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2015
• First Posted: January 26, 2015
• Study Start: March 19, 2015
• Primary Completion: June 2, 2016
• Study Completion: June 2, 2016
• Last Updated: February 21, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

NL (2)