52TiP - A phase 1 study of GBR 1302 in subjects with HER2-positive cancers

Date 05 November 2016
Event ESMO Symposium on Immuno-Oncology 2016
Session Lunch and general poster viewing
Presenter Martin Wermke
Citation Annals of Oncology (2016) 27 (suppl_8): viii4-viii17. 10.1093/annonc/mdw527
Authors M. Wermke1, H. Schmidt2, S. Ochsenreither3, J. Back4, Y. Salhi5, E. Bayever6
  • 1Hematology And Oncology, University Hospital Carl-Gustav-Carus, 01307 - Dresden/DE
  • 2Hematology And Oncology, Cellex GmbH, Cologne/DE
  • 3Hematology, Charité University of Medicine, Berlin/DE
  • 4Immunology, Glenmark Pharmaceuticals SA, La Chaux-De-Fonds/CH
  • 5Statistics, Glenmark Pharmaceuticals Europe Limited, Hertfordshire/GB
  • 6Oncology, Glenmark Pharmaceuticals Inc., Mahwah/US

Abstract

Aim/Background

GBR 1302 is a bispecific antibody targeting human CD3ε and human epidermal growth factor receptor 2 (HER2), which is overexpressed in tumors. GBR 1302 was built using the Glenmark BEAT® platform and designed to recruit cytotoxic T lymphocytes against HER2-positive cancer cells. Preclinically, GBR 1302 has demonstrated potent killing of HER2-overexpressing human cancer cells (HER2 3+ or 2+ by IHC HercepTest), as well as growth suppression of the trastuzumab-resistant cell line JIMT-1. In contrast, the GBR 1302 concentration required to kill primary cardiomyocytes with normal HER2 levels was up to 1000 times greater than the amount needed to kill HER2 3+ tumor cell lines. This study aims to determine the safety and tolerability of GBR 1302 monotherapy in subjects with HER2-positive cancers.

Trial design

Part 1 (dose-escalation) of this ongoing phase 1 study (NCT02829372) is enrolling adults with progressing HER2-positive solid tumors for which no standard or curative treatment is available. Intravenous GBR 1302 is given every 2 weeks in 28-day cycles at escalating doses (Table). Each of the first 4 cohorts includes a single subject; subsequent cohorts will enroll subjects using a standard 3 + 3 design. Primary endpoints are maximum tolerated dose (MTD) of GBR 1302, and the relationship of GBR 1302 dose with the incidence, nature, and intensity of adverse events (AEs). After Cycle 1, subjects continue GBR 1302 treatment until disease progression or unacceptable toxicity. Part 2 (expansion) of this study will enroll subjects at the MTD to further evaluate anti-tumor activity of GBR 1302, as well as safety and pharmacokinetics. Due to the known cardiotoxic potential of classic HER2-targeting strategies, this study incorporates a rigorous serological and echocardiographic surveillance schedule. The effects of GBR 1302 on the adaptive immune system will also be studied at a cellular and serological level in a translational research program.

n

Clinical trial identification

NCT02829372 (ClinicalTrials.gov), 2015-002926-38 (EudraCT)

Legal entity responsible for the study

N/A

Funding

Glenmark Pharmaceuticals S.A.

Disclosure

M. Wermke: Served as a consultant for Glenmark Pharmaceuticals. S. Ochsenreither: Served on advisory boards for lenmark Pharmaceuticals. J. Back: Full-time employee of Glenmark Pharmaceuticals SA. Y. Salhi: Full-time employee of Glenmark Pharmaceuticals Europe Limited. E. Bayever: Full-time employee of Glenmark Pharmaceuticals Inc. All other authors have declared no conflicts of interest.