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Proffered paper session - Developmental therapeutics

5879 - First-in-Human, First-in-Class study of the CD44v6 inhibitor AMC303 as monotherapy in patients with advanced epithelial tumors


21 Oct 2018


Proffered paper session - Developmental therapeutics


Clinical Research;  Translational Research

Tumour Site


Emiliano Calvo


Annals of Oncology (2018) 29 (suppl_8): viii133-viii148. 10.1093/annonc/mdy279


E. Calvo1, P.G. Aftimos2, A. Azaro3, M.J. de Miguel4, C. Jungels5, J. Zeron-Medina Cuairan6, P.G. Nuciforo7, P. Ehmer8, A. Martin9, H.K. Bender10, K. Dembowsky10

Author affiliations

  • 1 Start Phase I, Hospital Madrid Norte San Chinarro Centro Integral Oncologico Clara Campal, 28050 - Madrid/ES
  • 2 Phase I Unit, Institute Jules Bordet, 1000 - Brussels/BE
  • 3 Oncology Department, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 4 Start-madrid Phase 1 Unit, Hospital Madrid Norte San Chinarro Centro Integral Oncologico Clara Campal, 28050 - Madrid/ES
  • 5 Medical Oncology, Institute Jules Bordet, 1000 - Brussels/BE
  • 6 Medical Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 7 Molecular Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 8 Clinical Pharmacokinetics, Pharmacelsus GmbH, Saarbrücken/DE
  • 9 Research, amcure GmbH, 76344 - Eggenstein-Leopoldshafen/DE
  • 10 Clinical Development, amcure GmbH, 76344 - Eggenstein-Leopoldshafen/DE


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Abstract 5879


CD44v6 is an isoform of the CD44 family of transmembrane glycoproteins. High CD44v6 expression in epithelial cancer correlates with tumor growth, invasion, metastasis, and recurrence. CD44v6 is a co-receptor of the receptor tyrosine kinases c-Met, RON and VEGFR-2. Inhibition of CD44v6 blocks RTK activation and intracellular signaling processes. AMC303 is a highly selective inhibitor of CD44v6 with strong in vivo and in vitro anti-tumor activity.


This is a Phase I/Ib open label, non-randomized, multi-center study for patients with resistant advanced cancer (NCT03009214) with dose escalation based on a 3 + 3 design for all-comers (Part 1) and tumor type specific expansion cohorts at the Recommended Phase 2 Dose (RP2D) (Part 2). AMC303 was given IV, 0.1-20 mg/kg, in 30-60min. Tumor assessment (RECIST1.1) was performed every 6 weeks. A comprehensive biomarker program with paired tumor biopsies and plasma samples was established.


26 patients with a total of 11 different cancer types were treated in 6 dose levels with colorectal cancer as most frequent type. AMC303 infusions were very well tolerated, most drug-related AEs were grade 1 and 2 (in 46% of patients). No related SAEs were reported. Most frequently reported related events were infusion related reactions and hypersensitivity (grade 1-2, in 22% of patients), followed by nausea, diarrhoe and fatigue. MTD was not achieved. PK analysis revealed a linear dose-exposure relationship, t1/2 of 4-7h, CL of 40-60 mL/h/kg. 81% of patients received at least 6 weeks of therapy. No objective responses were observed in this unselected patient population during the dose escalation phase. More than 70% of tumors were CD44v6 positive by IHC, and 50% exhibited strong to moderate expression with no change after 3 weeks. Biomarker analyses by IHC (Ki67, S6, c-Met, Akt, MAPK), protein profiling of tumor lysates and plasma revealed up- and down-regulation of several biomarkers at 3 weeks. The optimal biological dose was established as 10 mg/kg based on PK/PD data.


AMC303 was demonstrated to be well-tolerated with a favorable PK profile. Part 2 is designed to test anti-tumor activity, including patients with high expression of CD44v6 in specific tumor types.

Clinical trial identification


Legal entity responsible for the study

Amcure GmbH.


Amcure GmbH.

Editorial Acknowledgement


P. Ehmer: Employee: Pharmacelsus GmbH. A. Martin, H.K. Bender, K. Dembowsky: Employee: Amcure GmbH. All other authors have declared no conflicts of interest.

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