Antibody-Drug Conjugates for Lung Cancer: Payloads and Progress

Antibody Drug Conjugates (ADCs) are a novel class of therapeutic that structurally comprise an antibody directed at a tumor epitope connected via a linker to a cytotoxic payload that have shown significant antitumor activity across a range of malignancies including lung cancer. In this article we review the pharmacology of ADCs, describe results of trials with ADCs directed at targets in lung cancer including Trophoblast cell-surface antigen 2(TROP2), HER3, MET, Carcinoembryonic antigen-related cell adhesion molecular 5(CECAM-5) and HER2. Trastuzumab Deruxtecan (also known as DS-8201a or T-DXd) an ADC directed at HER2 recently became the first ADC to receive FDA approval in lung cancer, on the basis of its activity in tumors with HER2 mutations, demonstrated in the Destiny-Lung01 and Lung02 trials.