MO31-4 Phase 1b/2 trial of tucatinib+trastuzumab+/-chemotherapy or pembrolizumab in patients with metastatic HER2+ GI cancers

Abstract

Human epidermal growth factor receptor 2 (HER2) gene amplification or protein overexpression (HER2+) occurs in many gastrointestinal (GI) cancers. Tucatinib (TUC) is a highly selective HER2-directed tyrosine kinase inhibitor with minimal EGFR inhibition, approved for HER2+ metastatic breast cancer. In patient-derived xenograft models of HER2+ GI tumors, TUC+trastuzumab (T) showed superior anti-tumor activity compared with either agent alone (Kulukian 2020). In the MOUNTAINEER study, TUC+T in HER2+ metastatic colorectal cancer (CRC) resulted in an objective response rate of 52% (interim results, Strickler 2019).