HER2 Directed Antibody-Drug-Conjugates beyond T-DM1 in Breast Cancer

Gabriel Rinnerthaler; Simon Peter Gampenrieder; Richard Greil

doi:10.20944/preprints201902.0043.v1

Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 3 February 2019 / Approved: 4 February 2019 / Online: 4 February 2019 (17:01:31 CET)

Since the discovery of the human epidermal growth factor receptor 2 (HER2) as an oncogenic driver in a subset of breast cancers and the development of HER2 directed therapies, the prognosis of HER2 amplified breast cancers has increased meaningfully. Next to monoclonal anti-HER2 antibodies and tyrosine kinase inhibitors, the antibody-drug conjugate T-DM1 is a pillar of targeted treatment of advanced HER2-positive breast cancers. Currently, several HER2 directed antibody-drug conjugates are under clinical investigation for HER2 amplified but also HER2 expressing but not amplified breast tumors. In this article, we review the current preclinical and clinical evidence of the investigational drugs A166, ALT-P7, ARX788, DHES0815A, DS-8201a, RC48, SYD985, MEDI4276 and XMT-1522.

ADC; HM2-MMAE; (vic-)trastuzumab duocarmazine; Trastuzumab deruxtecan; TAK-522; Trastuzumab emtansine; anti-HER2/PBD-MA; HER2 low; HER2-low; mode of action

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HER2 Directed Antibody-Drug-Conjugates beyond T-DM1 in Breast Cancer

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