Phase 1 study of ZW25, a bispecific anti-HER2 antibody, in patients with advanced HER2-expressing cancers.

TPS215Background: HER2 is expressed above normal levels by many cancers, including a range of gastrointestinal tumors. While HER2 can contribute to tumor growth and survival even when expressed at low levels, antibody-based HER2 targeted therapy has shown efficacy only in breast (trastuzumab [T], pertuzumab [P]) or gastric cancers (T) with the highest levels of HER2 expression or gene amplification. Therefore, there remains significant medical need, particularly for cancers with lower HER2 levels or more heterogeneous patterns of expression. ZW25 is a novel humanized bispecific antibody directed against two distinct epitopes of HER2. The unique structure of ZW25 leads to greater cell decoration and receptor internalization than T, even in the setting of low levels of HER2 expression. In preclinical models, ZW25 has demonstrated greater activity than T in both HER2 high and HER2 low-expressing cancers, including gastric cancer. This first-in-human study will evaluate the safety and preliminary anti-tumor a...