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Antibody Drug Conjugates ADC

05:35 EST 16th December 2018 | BioPortfolio

The humanized anti-Her2 monoclonal antibody Herceptin (trastuzumab) has become the mainstay in the treatment of Her2-positive breast cancer. Combining trastuzumab with the potent cytotoxic DM1 via a stable linker resulted in the antibody-drug conjugate (ADC) trastuzumab-DM1. Genentech and Roche are conducting phase III trials of trastuzumab-DM1 in women with advanced HER2-positive breast cancer whose disease has progressed after receiving initial treatment. Results of previous phase II investigation showed an impressive 33 % objective response rate in 110 women with advanced (metastatic) HER2-positive breast cancer that had worsened despite having already received an average of seven drugs for metastatic disease, including chemotherapy, trastuzumab and lapatinib. These data highlight the enormous potential of ADCs in the treatment of cancer although the first ADC approved by the FDA voluntarily will be withdrawn from the market. The required post-marketing study did not confirm the clinical benefit of Mylotarg in previously untreated AML.

With two ADCs in phase III evaluation and at least 16 different ADCs in clinical phase I and II evaluation, ADC technology is on the verge of becoming an established antibody potentiation technology of great interest for providers of the technology and antibody developers. Improvements in linker technology, progress with the cytotoxic payload and more diligently designed and executed clinical studies will contribute to the success of the technology.

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