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Antibody-drug conjugates select ADCs) were initially developed to provide a selective targeting mechanism for cytotoxic small molecule drugs with the goal of improving the therapeutic index in clinical practice. But despite a careful target selection and a high degree of specificity afforded through the antibody part of the ADC, a sufficiently improved therapeutic index has been challenging to achieve. It often remains a challenge to reach desirable efficacious doses with repeated cycles of treatment due to the toxicity profile induced by the cytotoxic warhead. The clinical landscape of ADC therapeutics in both hematological and solid cancers has grown in recent years considerably to nearly 600 clinical trials incorporating numerous ADC modalities. These new molecular entities utilize many different tumor-associated antigen targets, new conjugation technologies, and payload warheads of various mechanisms such as tubulin inhibitors, DNA damaging, topoisomerase inhibition, or DNA polymerase II inhibitors.
Since the concept of a “magic bullet” for targeted drugs was coined about a century back, the approvals of brentuximab anti-CD33-ADC vedotin select in 2011) anti-HER2 ADC trastuzumab emtansine select in 2013) and Mylotarg CD33-Calicheamicin ADC select in 2017) have revolutionized the development of ADCs with over 250 clinical trials and more than 60 distinct ADC molecules currently in development. Despite this revolutionary growth, the low therapeutic index or limited safety window of ADCs has posed a significant challenge in achieving success for the treatment of solid tumors. Join us for this exciting GEN webinar where our expert panelist will discuss current strategies for increasing tumor cytotoxicity while decreasing drug toxicity, as well as the general, overall improvement of the therapeutic index for ADCs.
A live Q&A session will follow the presentations, offering you a chance to pose questions to our expert panelists.
Produced with support from:
Panelist
Rakesh Dixit, PhD, DABT
Vice President, R&D
Global Head, Translational Sciences-Biologics Safety Assessment
MedImmune select A Member of AstraZeneca Group)