Issues

Dienstmann and colleagues found that Sym004, a mixture of two recombinant monoclonal antibodies targeting nonoverlapping EGFR epitopes, induced significant EGFR degradation and growth inhibition in a panel of colorectal cancer cell lines in the presence of EGFR ligands. In a first-in-human phase I trial, Sym004 treatment resulted in sustained EGFR downregulation in tumor samples and was associated with grade 3 skin toxicities and hypomagnesemia that were consistent with known adverse events of anti-EGFR drugs and manageable with dose reductions and supportive care. Furthermore, Sym004 induced tumor shrinkage in 17 (44%) patients with metastatic colorectal cancer and acquired resistance to anti-EGFR therapy, including 5 (13%) patients who achieved a partial response. These findings demonstrate that Sym004 has clinically relevant antitumor activity and may overcome cetuximab or panitumumab resistance in patients with metastatic colorectal cancer. For details, please see the article by Dienstmann and colleagues on page 598.