EZH117208: Phase I Dose Escalation Study of GSK2816126
Research type
Research Study
Full title
A phase I open-label, dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of GSK2816126 in subjects with relapsed/refractory diffuse large B cell and transformed follicular lymphoma
IRAS ID
139567
Contact name
Peter Johnson
Contact email
Sponsor organisation
GlaxoSmithKline
Eudract number
2013-001585-42
Research summary
Diffuse Large B-Cell Lymphoma (DLBCL) and transformed Follicular Lymphoma (FL) are sub-types of B-cell Non-Hodgkin’s Lymphoma (NHL), a cancer of the white blood cells. NHL is the 6th most common form of cancer and is responsible for approximately 4500 deaths per year in the UK.
NHL survival rates are slowly improving with 1st line Rituximab treatment being partly responsible for this. However, the treatment options beyond 1st line are limited and the outlook for patients is poor, with relapse expected within 12 months. Thus, there is a real need to identify new compounds which may demonstrate benefit and improve survival rates further. This is the first study of GSK2812126 (an inhibitor of the EZH2 enzyme complex) to be conducted in human subjects with relapsed and/or refractory lymphoma malignancies for which no standard therapies are anticipated to result in a durable remission.
Current data from preclinical development is promising in DLBCL lines, in particular of the sub-type Germinal Centre B-Cell (GCB), but it is unknown if GSK2816126 will have efficacy in GCB-DLBCL patients. Data obtained in this study may assist in progressing the knowledge base on GCB-DLBCL and its treatment, or help identify individuals more likely to benefit or have side-effects from GSK2816126.
This Phase I trial will comprise 2 parts; Part 1 is a dose escalation study to select the recommended Part 2 dose (RP2D) based on safety, PK and PD profiles observed after IV administration; Part 2 consists of two expansion cohorts for GCB-DLBCL patients with and without EZH2 mutations and therefore EZH2 mutation status will need to be determined via analysis of tumour samples. This part will further explore clinical activity and will primarily determine objective response rates.
Approximately 50 patients will be followed in the UK; 20 in Part 1 and 30 in Part 2.REC name
London - City & East Research Ethics Committee
REC reference
14/LO/0044
Date of REC Opinion
24 Jan 2014
REC opinion
Favourable Opinion