Antibody Drug Conjugates: Future Directions in Clinical and Translational Strategies to Improve the Therapeutic Index.

Antibody Drug Conjugates: Future Directions in Clinical and Translational Strategies to Improve the Therapeutic Index. Clin Cancer Res. 2019 Apr 12;: Authors: Coats S, Williams M, Kebble B, Dixit R, Tseng L, Yao NS, Tice DA, Soria JC Abstract Since the first approval of gemtuzumab ozogamicin (Mylotarg; CD33 targeted), 2 additional antibody drug conjugates (ADCs)-brentuximab vedotin (Adcetris; CD30 targeted) and inotuzumab ozogamicin (Besponsa; CD22 targeted)-have been approved for hematologic cancers and 1 ADC, trastuzumab emtansine (Kadcyla; HER2 targeted), has been approved to treat breast cancer. Despite a clear clinical benefit being demonstrated for all 4 approved ADCs, the toxicity profiles are comparable to those of standard-of-care chemotherapeutics, with dose-limiting toxicities associated with the mechanism of activity of the cytotoxic warhead. However, the enthusiasm to develop ADCs has not been dampened; approximately 80 ADCs are in clinical development in nearly 600 clinical trials, and 2 to 3 novel ADCs are likely to be approved within the next few years. While the promise of a more targeted chemotherapy with less toxicity has not yet been realized with ADCs, improvements in technology combined with a wealth of clinical data are helping to shape the future development of ADCs. In this review we discuss the clinical and translational strategies associated with improving the therapeutic index for ADCs. PMID: 30979...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research