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Antibody-drug conjugates in lung cancer: dawn of a new era?

*January 2023*

Note: This is a deep dive into ADCs that are currently being used inside and outside clinical trials for lung cancers expressing HER2 or HER3 mutations as well as other mutations that occur after first- and second-line therapies.

Antibody-drug conjugates (ADCs) are, arguably, the fastest-growing class of oncology drugs in development, and while not a new concept, the potential to change clinical practice is vast. In lung cancer, the treatment paradigm has shifted dramatically in recent years, and now incorporates targeted therapy, immunotherapy, and systemic chemotherapy, and ADCs are now joining the list as potential options for lung cancer patients.

ADCs are unique in offering the potential to deliver highly potent cytotoxic agents to cancer cells that express a pre-defined cell surface target, thereby harnessing the powers of both cytotoxic chemotherapy and targeted therapy. Thus, ADCs are agents of precision oncology, and using these targeting properties one can greatly enhance the therapeutic index of the attached payload, compounds that would otherwise be too toxic for use. Comprising of three key components, ADCs are the “homing missiles” of modern drug development, and include (1) a monoclonal antibody that binds selectively to an antigen on the tumor cell surface, (2) a cytotoxic drug payload, and (3) a cleavable or non-cleavable linker1,2. To date, twelve ADCs have been granted FDA approval in oncology (Table 1), and with nine of these approved since 2017, the pace of development of this class is only accelerating. Read more.

Watch an ADC primer video here.