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Novel antibody-drug conjugates (ADCs) have been explored in a number of early-stage clinical trials, both as single-agents and in combinations for patients with lymphoid malignancies. These novel approaches are moving outside of the established paradigm of targeting CD30 to include CD19, CD22, and CD79B, notes Myron S. Czuczman, MD. The construct of these agents is similar, with a cytotoxic linked to an antibody. The agents being explored utilize linker technology from ImmunoGen and Seattle Genetics, Czuczman points out.
The exploration of ADCs has not been without setbacks. In May 2013 a phase III study exploring the CD22 ADC inotuzumab ozogamicin in patients with aggressive non-Hodgkin lymphoma was halted after interim data showed the agent was unlikely to improve survival. Additionally, Czuczman notes, antibodies targeting CD20 are not being explored, since these antibodies are poorly internalization.
Following the success of brentuximab vedotin and the ADC T-DM1 in breast cancer, ADCs are viewed at as a new class of agents, believes Anas Younes, MD. The next step in the evolution for this class will be combinations with biologics or chemotherapy. It is likely that the most appropriate combination for each agent will need to be explored on a case-by-case basis, believes Lauren C. Pinter-Brown, MD.