Primary: To evaluate the safety of GSK2849330 in a larger population of subjects in molecularly-defined tumor histology groups at the dose regimen(s) recommended for further exploration in Part 1. Secondary: Clinical benefit, pharmacodynamics,…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Adverse events.
Secondary outcome
Drug plasma concentration, antibodies against GSK2849330, response evaluation
(RESIST 1.1).
Background summary
The HER family of receptor tyrosine kinases is comprised of HER1 (EGFR), HER2
(ErbB2), HER3 (ErbB3) and HER4 (ErbB4). HER3 is capable of potent signaling
through the PI3K pathway leading to proliferation.
Monoclonal antibodies offer an ideal means of blocking both ligand dependent
and independent signaling as well as targeting cells over-expressing HER3 for
destruction. To this end GSK2849330, a monoclonal antibody specific to HER3, is
being developed. This first in human study is designed to assess the safety,
tolerability and pharmacokinetics of GSK2849330 as well as looking for
preliminary evidence of target engagement in subjects with advanced HER3
positive tumors. An understanding of the distribution of GSK2849330 into tumor
tissue and its interaction with HER3 would help to determine an optimal dose
level to be taken forward for further clinical development.
Part 1 is the phase I dose-escalation part of the study, which has been
performed outside the Netherlands. The Netherlands will participate in Part 2,
the phase II part to assess safety and preliminary clinical benefit of the
dose(s) of GSK2849330, selected for phase II based on phase I data.
This ABR form provides information about Part 2 of the study only.
Study objective
Primary: To evaluate the safety of GSK2849330 in a larger population of
subjects in molecularly-defined tumor histology groups at the dose regimen(s)
recommended for further exploration in Part 1.
Secondary: Clinical benefit, pharmacodynamics, pharmacokinetics,
immunogenicity.
Study design
Open-label, non-comparative phase 2 study with 4 groups with different, defined
tumor histologies (see protocol page 21). 12-30 subjects per group.
Prescreening of tumor tissue (archival or fresh) for HER3 or HER3 and NRG1.
Treatment until unacceptable side effects or disease progression.
GSK2849330 will be given by IV infusion over 1 hour.
Intervention
Treatment with GSK2849330.
Study burden and risks
Risk: adverse events of study treatment.
Burden: prescreening, screening, 5 visits during 1st treatment month,
thereafter every 1-2 weeks (initially infusions every week; later on option to
change to every 2 weeks).
Physical examination every 4 weeks.
Blood tests 15-50 mL every visit.
Pregnancy test every 4 weeks.
Scan(s) every 8 weeks.
ECG every 4 weeks.
Optional pharmacogenetic testing (6 mL blood)
2-3 tumor biopsies [screening, treatment day 15 and (optional) at disease
progression].
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Listed location countries
Age
Inclusion criteria
• Written informed consent obtained.
• Males and females >=18 years of age.
• ECOG status 0 or 1.
• Sufficient archival tumor specimen is available for HER3 (± NRG1) analysis or willingness to provide fresh tumor sample.
• Previously treated, unresectable stage III-IV melanoma, gastric/gastroesophageal cancer, head and neck cancer, or non small cell lung cancer, who are HER3 positive or (HN cancer or NSCLC) HER3 and NRG1 positive, see protocol page 23-25 for details.
• Adequate contraception for females of childbearing potential (see protocol page 22-23 for details).
• Men with a female partner of childbearing potential must agree to use effective contraception (see protocol page 23 for details).
Exclusion criteria
• Untreated brain or meningeal metastases or spinal cord compression (see protocol page 25 for details).
• Prior HER3- directed treatment.
• Use of a prohibited medication (see protocol section 10.2).
• Evidence of significant cardiovascular risk (see protocol page 26 for details).
• Pregnancy or lactation.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-001699-39-NL |
| Other | gsk-clinicalstudyregister.com; registratienummer 117158 |
| CCMO | NL51818.042.15 |