6533b82afe1ef96bd128cab2

RESEARCH PRODUCT

A phase I study of the bispecific antibody T-cell engager GBR 1302 in subjects with HER2-positive cancers.

subject

description

TPS3091 Background: GBR 1302, a bispecific antibody based on Glenmark’s BEAT platform, is designed to recruit cytotoxic T-cells (independent of their specificity) to HER2-positive cancer cells where they are activated by the CD3e-specific domain of the molecule. Preclinically, GBR 1302 has demonstrated potent killing of HER2-positive 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 concentration needed to kill HER2 3+ tumor cell lines. This study will determine safety and tolerability of GBR 1302 monotherapy in subjects with HER2-positive cancers. Methods: Part 1 (dose-finding) of this ongoing phase 1 study (NCT02829372) is enrolling adults with progressing HER2-positive solid tumors for which no standard 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 enroll subjects using a standard 3+3 design. Primary endpoints are: maximum tolerated dose (MTD) of GBR 1302; and relationship of GBR 1302 with the incidence, nature, and intensity of adverse events. After Cycle 1, subjects continue GBR 1302 treatment until disease progression or unacceptable toxicity. Part 2 (expansion) will treat subjects at the MTD to further evaluate anti-tumor activity, 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 cellular and serological levels in translational research. Clinical trial information: NCT02829372. [Table: see text]