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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

Date

11 Sep 2017

Session

Poster display session

Topics

Cytotoxic Therapy;  Clinical Research

Presenters

Emiliano Calvo

Citation

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

Authors

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
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Resources

Abstract 4454

Background

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

Funding

None

Disclosure

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

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