0000000000410016
AUTHOR
Ulla H. Hansen
Safety and Activity of the First-in-Class Sym004 Anti-EGFR Antibody Mixture in Patients with Refractory Colorectal Cancer
Abstract Tumor growth in the context of EGFR inhibitor resistance may remain EGFR-dependent and is mediated by mechanisms including compensatory ligand upregulation and de novo gene alterations. Sym004 is a two-antibody mixture targeting nonoverlapping EGFR epitopes. In preclinical models, Sym004 causes significant EGFR internalization and degradation, which translates into superior growth inhibition in the presence of ligands. In this phase I trial, we observed grade 3 skin toxicity and hypomagnesemia as mechanism-based dose-limiting events during dose escalation. In dose-expansion cohorts of 9 and 12 mg/kg of Sym004 weekly, patients with metastatic colorectal cancer and acquired EGFR inhi…
Phase 1 study of biweekly (Q2W) anti-EGFR monoclonal antibody (mAb) mixture Sym004 in patients (pts) with metastatic colorectal cancer (mCRC) resistant to previous anti-EGFR treatment.
3551 Background: Preclinical models suggest that WT KRAS mCRC may retain EGFR dependency despite resistance developed to anti-EGFR mAb treatment (eg, cetuximab or panitumumab). Sym004 is the first-...