Dr. Shu on the MOA of Amivantamab in EGFR Exon 20 Insertion–Mutated NSCLC

Catherine Ann Shu, MD, clinical director of Thoracic Medical Oncology Service, Department of Medicine, Division of Hematology/Oncology at Herbert Irving Comprehensive Cancer Center, Columbia University, discusses the mechanism of action of amivantamab (JNJ 61186372) in patients with EGFR exon 20 insertion–mutated non–small cell lung cancer.

The bispecific monoclonal antibody amivantamab was developed to simultaneously target 2 pathways that are the primary drivers in certain subpopulations of NSCLC, such as those with EGFR mutations and MET amplifications, Shu says. The agent has several unique mechanisms of action, Shu adds. By binding to the external domain of the EGFR receptor, its action is not dependent upon the nature of the activating mutation that typically occurs within the interior of the cell.

Moreover, EGFR exon 20 mutations pose a unique challenge in NSCLC despite being the third most common mutation, Shu says. This is due to the fact that patients with this mutation tend to be less sensitive to EGFR TKIs because of steric hindrance that occurs at the TKI binding site. The unique mechanism of action of amivantamab allows it to have activity against EGFR exon 20 mutations, Shu concludes.

In March 2020, amivantamab was granted a breakthrough therapy designation by the FDA in both the United States and China.