Phase I dose-escalation trial of Sym004, a mixture of two anti-EGFR antibodies, in Japanese patients with advanced solid tumors.

2522Background: Sym004 is a 1:1 mixture of two chimeric IgG1 antibodies targeting non-overlapping epitopes of the epidermal growth factor receptor (EGFR). Binding of both antibodies to EGFR leads to its internalization and degradation. The resulting down-regulation of EGFR results in antitumor activity that is superior to that of cetuximab and panitumumab in preclinical models; Sym004 can also overcome acquired resistance to cetuximab in vivo. We have evaluated the safety of Sym004 in Japanese patients (pts) with advanced solid tumors. Methods: Japanese adults aged ≥ 20 years with refractory or recurrent late-stage solid tumors, ECOG status of 0 or 1, and life expectancy of at least 3 months were eligible for the dose-escalation part of the trial (Part A). Sym004 doses tested were 6 mg/kg weekly (n = ’3+3’), 9 mg/kg loading dose followed by 6 mg/kg weekly (n = 6), 12 mg/kg weekly (n = 6), and 18 mg/kg q2w (n = 6). An expansion cohort of pts with esophageal squamous cell carcinoma (ESCC) (Part B) was enrol...