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Antibody-Drug Conjugates for Lung Cancer: Payloads and Progress

*May 2023*

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.

  • Traztuzumab deruxtecan (T-DXd) is the first antibody-drug conjugate (ADC) approved for lung cancer on the basis of activity in patients with HER2 mutation–positive non–small-cell lung cancer demonstrated in the DESTINY-Lung01 and DESTINY-Lung02 trials.
  • ADCs directed at additional targets, including TROP-2, HER3, MET, CEACAM5, and DLL2, are being clinically evaluated in a range of settings as monotherapy and in combination with other agents including immunotherapy.
  • Although ADCs will likely become established as additional treatment options for lung cancer, there remains a need to develop strategies for optimal patient selection and to overcome resistance to treatment.

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