A phase I study of MEHD7945A (MEHD), a first-in-class HER3/EGFR dual-action antibody, in patients (pts) with refractory/recurrent epithelial tumors: Expansion cohorts.
2017
2568 Background: Dysregulated human epidermal growth factor receptor tyrosine kinase (HER RTK) signaling is an important driver of tumor growth, metastasis, and survival. Extensive co-expression and heterodimerization suggest that simultaneous blockade of multiple HER RTKs may be more effective than blockade of a single RTK. MEHD is a novel dual-action human IgG1 antibody. Each antigen-binding fragment blocks ligand binding to HER3 or EGFR, and intended to inhibit signaling from all major ligand-dependent HER dimers. MEHD has single-agent activity in multiple tumor models including models resistant to anti-HER3 or anti-EGFR. Methods: This Phase I study evaluated safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) activity of intravenous MEHD every 2 weeks (q2w). Tumor PD assessments were pre- and post-dose FDG-PET and IHC for pS6, pPRAS40 or pERK in tumor biopsies. Tumor CT assessments were performed q8w. No dose-limiting toxicity (DLT) was observed in six 3+3 cohorts from 1-30 mg/kg (n=...
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