Targeting Treatment-Resistant Colorectal Cancers
A first-in-class antibody mixture shows clinical activity against treatment-resistant, advanced colorectal cancers.
In an early-phase trial, an antibody mixture that targets two regions of the epidermal growth factor receptor (EGFR) was found to be clinically active in patients whose colorectal cancers had become resistant to earlier anti-EGFR treatment.
Patients with advanced colorectal tumors without mutations in the RAS genes benefit substantially from anti-EGFR therapies, but the cancers develop resistance and eventually progress, said study senior author Josep Tabernero, MD, PhD, head of the medical oncology department at Vall d’Hebron University Hospital and director of the Vall d’Hebron Institute of Oncology in Barcelona, Spain.
The new antibody mixture called Sym004 “is a 1:1 mixture in the same infusion bag of two antibodies that bind to different regions of the extracellular domain of EGFR,” explained Dr. Tabernero.
Like the U.S. Food and Drug Administration-approved anti-EGFR antibodies cetuximab and panitumumab, Sym004 antibodies block EGFR. The double-targeting of EGFR by Sym004, however, causes superior EGFR internalization and degradation, which is likely to provide better outcomes than cetuximab or panitumumab, Dr. Tabernero added.
In the phase I trial, Sym004 was found to be clinically active in patients with advanced colorectal cancer that had become resistant to prior anti-EGFR therapies.
“This study represents one of the first examples of promising translation from preclinical findings to drug development and clinical activity against anti-EGFR antibody-resistant colorectal cancer,” said Dr. Tabernero. “The significant antitumor activity of Sym004 in patients whose tumors have become resistant to anti-EGFR therapies suggests that some colorectal cancers that progress after treatment with cetuximab or panitumumab remain dependent on EGFR signaling.”