Senologie - Zeitschrift für Mammadiagnostik und -therapie 2019; 16(02): e22-e23
DOI: 10.1055/s-0039-1688002
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

Matching the critical function of the biosimilar ABP 980 and Trastuzumab

HC Kolberg
1   Marienhospital Bottrop gGmbH, Schwerpunkt Gynäkologische Onkologie, Spezielle Operative Gynäkologie, Bottrop, Deutschland
,
MA Colleoni
2   Divisione of Medical Senology, European Institute of Oncology, Mailand, Italien
,
Z Tomasevic
3   Institute for Oncology and Radiology of Serbia, Belgrad, Serbien
,
O Ponomarova
4   R.E. Kavetsky Institute of Experimental Pathology, Kiew, Ukraine
,
HJ McBride
5   Amgen Inc., Thousand Oaks, Vereinigte Staaten von Amerika
,
H Tesch
6   Hämatologisch-Onkologische Gemeinschaftspraxis, Frankfurt am Main, Deutschland
,
V Hanes
5   Amgen Inc., Thousand Oaks, Vereinigte Staaten von Amerika
› Author Affiliations
Further Information

Publication History

Publication Date:
28 May 2019 (online)

Also available at
 

Background:

Biosimilarity of ABP 980 to the reference product (RP) trastuzumab was proven using robust analytical and functional assessments. Phase 1 and phase 3 studies have shown pharmacokinetics and clinical similarity to trastuzumab. Here, we extend the similarity assessment using multiple orthogonal assays for the primary mechanism of action.

Methods:

Multiple lots of ABP 980, trastuzumab (US and EU RPs) were compared in the biological activity assessment. We conducted characterization assays assessing human epidermal growth factor receptor 2 (HER2) cell binding, inhibition of HER2 signaling, inhibition of HER2 ligand-independent proliferation in gastric cancer cells (NCI-N87), and a synergy study was conducted with docetaxel chemotherapy in gastric cancer cells.

Results:

Relative cell binding to HER2 was similar (ABP 980, 93%-112%; trastuzumab [EU], 98%-109%; trastuzumab [US], 96%-102%). Synergy scores (mean ± SD) with docetaxel (in NCI-N87 cells) for ABP 980, trastuzumab (US and EU RPs), respectively, were 16.1 ± 1.4, 16.4 ± 1.8, and 15.8 ± 1.3. Functionally, ABP 980 and trastuzumab

similarly inhibited HER2 ligand-independent proliferation in NCI-N87 gastric cancer cells, exhibited specificity against MCF7 non-amplified HER2 expressing breast cancer cells, and showed similar inhibition of pAkt phosphorylation in BT-474 breast cancer cells.

Conclusions:

In this study, ABP 980 and trastuzumab RPs showed similar activity, either alone or in combination with docetaxel, in both breast cancer and gastric cancer cell lines. Our results add to the totality of evidence supporting ABP 980 biosimilarity to trastuzumab, as required for its approval and scientific justification for extrapolation across approved indications.