Phase I trial of the first-in-class EGFR antibody mixture, Sym004, in patients with advanced solid tumors

3089 Background: Sym004 is a recombinant antibody 1:1 mixture of two chimeric anti-EGFR mAbs, which elicits superior cancer cell growth inhibition in preclinical models. Uniquely, Sym004 mediates cell surface receptor removal by triggering EGFR internalization and degradation. Results from a first-in-human multicenter trial evaluating safety and tolerability of multiple doses of Sym004 are reported. Methods: The trial comprises a dose-escalating part A (0.4 mg/kg-12 mg/kg) with classical 3+3 design after the first 2 cohorts and an extension part B at maximum tolerated dose (MTD). Patients (pts) received weekly IV infusions of Sym004 until disease progression or unacceptable toxicity. Pharmacokinetics and safety is evaluated weekly, with dose-limiting toxicities (DLT) assessed in the first 4 weeks, and tumor response every 8 weeks. Results: In part A, 17 pts (median age 60 years) were treated with doses up to 9 mg/kg without reaching the MTD: 0.4 mg/kg (1 had 6 doses), 0.75 mg/kg (1 had 35* doses), 1.5 mg/...