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Poster display session

4454 - First-in-Human study of AMC303 as monotherapy in patients with advanced solid tumor of epithelial origin


11 Sep 2017


Poster display session


Cytotoxic Therapy;  Clinical Research


Emiliano Calvo


Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367


E. Calvo1, P. Aftimos2, A. Azaro3, M. de Miguel1, C. Jungels4, P. Nuciforo5, P. Ehmer6, H. Bender7, K. Dembowsky8

Author affiliations

  • 1 Medical Oncology, START Madrid, Centro Integral Oncologico Clara Campal, 28050 - Madrid/ES
  • 2 Clinical Trials Conduct Unit, Institute Jules Bordet, 1000 - Brussels/BE
  • 3 Molecular Therapeutics Research Unit, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 4 Medical Oncology, Jules Bordet, Brussels/BE
  • 5 Molecular Oncology Group, Vall d´Hebron Institute of Oncology, 08035 - Barcelona/ES
  • 6 Analytics, Pharmacelsus GmbH, 66123 - Saarbrücken/DE
  • 7 Clinical Development, amcure GmbH, 76344 - Eggenstein-Leopoldshafen/DE
  • 8 Management, amcure GmbH, 76344 - Eggenstein-Leopoldshafen/DE


Abstract 4454


CD44v6 is an isoform of the CD44 family of transmembrane glycoproteins for hyaluronan. High CD44v6 expression was correlated with tumor invasion, metastasis, recurrence and chemoresistance. CD44v6 is a co-receptor of the receptor tyrosine kinases c-Met, RON and VEGFR-2 that play a critical role in the development and progression of many types of cancer. Inhibition of CD44v6 efficiently blocks activation of c-Met, RON and VEGFR-2 and intracellular downstream signaling processes. AMC303 is a highly specific and selective inhibitor of CD44v6 for which strong anti-tumor activity was demonstrated in vitro and in vivo. In xenotransplantation animal models, intermittent application of AMC303 resulted in a marked reduction of the primary tumor, prevention of metastatic spread and regression of existing metastases. Good safety and tolerability were demonstrated in pre-clinical studies. The starting dose of 0.1 mg/kg and dose escalation steps are based on the safety profile and are supported by modelling of human pharmacokinetic (PK) profiles from animal exposure studies. Blocking of CD44v6 by AMC303 represents a novel and promising approach to block cancer related RTK pathways by an extracellular acting drug.

Trial design

A First-in-Human Phase I/Ib study in cancer patients was initiated (NCT03009214). The study was designed as a two part open-label, non-randomized, multicentre, dose escalation study with a 3 + 3 design (Part 1) and an expansion cohort at the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) (Part 2). Inclusion and exclusion criteria are: Type of cancer (e.g. epithelial cancer for which CD44v6 is known to be highly expressed), ECOG status 0-2, and adequate hematological, renal and hepatic function. Cancer patients are enrolled after failure of conventional therapy or for whom no standard treatment is available. The primary endpoints in Part 1 are safety and tolerability and PK properties. The effects of AMC303 on RTK pathways are analysed in plasma samples (ELISA and Luminex) and mandatory tumor biopsies (immunohistochemistry, protein profiling). Part 2 will focus on selected tumor types as evaluated from the pharmacological effects of AMC303 in part 1.

Clinical trial identification

EudraCT number: 2016-001358-16

Legal entity responsible for the study

Amcure GmbH




H. Bender, K. Dembowsky: Employee by amcure GmbH and stock holder. All other authors have declared no conflicts of interest.

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