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Zirconium-89 (89Zr)-labeled bispecific T-cell engager (BiTE®) AMG 211 PET imaging to determine AMG 211 biodistribution in patients with gastrointestinal (GI) adenocarcinomas

Date

22 Oct 2018

Session

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

Presenters

Kirsten Moek

Citation

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

Authors

K.L. Moek1, S.J.H. Waaijer2, I.C. Kok2, F.V. Suurs2, A. Brouwers3, C.W. Menke-van der Houven van Oordt4, T.T. Wind2, J.A. Gietema1, C.P. Schroder2, S.V.K. Mahesh3, A. Jorritsma-Smit5, M.N. Lub-De Hooge5, R.S.N. Fehrmann1, D.J. de Groot1, E.G..E. de Vries1

Author affiliations

  • 1 Medical Oncology, University Medical Center Groningen, 9700 RB - Groningen/NL
  • 2 Medical Oncology, University Medical Center Groningen, Groningen/NL
  • 3 Radiology, Nuclear Medicine And Molecular Imaging, University Medical Center Groningen, Groningen/NL
  • 4 Medical Oncology, VUMC Cancer Center Amsterdam, Amsterdam/NL
  • 5 Clinical Pharmacy And Pharmacology, University Medical Center Groningen, Groningen/NL
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Resources

Background

AMG 211 is a ∼55 kDa BiTE® antibody construct directed against carcinoembryonic antigen (CEA, CEACAM5) on tumor cells and cluster of differentiation 3 (CD3) on cytotoxic T-cells. Biodistribution of bispecific antibodies in humans is largely unknown. Therefore, we performed a first-in-human feasibility study with 89Zr-AMG 211 as PET tracer to explore AMG 211 biodistribution in normal and tumor tissues.

Methods

Nine patients with advanced GI adenocarcinomas underwent 89Zr-AMG 211 PET imaging before (n = 7), during (n = 1) or before and during (n = 1) AMG 211 treatment. Before AMG 211 treatment, a fixed dose of 37 MBq 200 µg 89Zr-AMG 211 alone (n = 2), or in combination with 1,800 µg (n = 4) or 4,800 µg (n = 2) cold AMG 211 was administered over 3 hours (h) followed by PET scans at 3, 6, and 24 h. 89Zr-AMG 211 uptake was measured as standardized uptake value (SUV). 89Zr-AMG 211 integrity in plasma and urine was analyzed with gel electrophoresis and binding of 89Zr-AMG 211 to immune cells by counting Ficoll separated whole blood fractions.

Results

Before AMG 211 treatment, the optimal imaging dose was 200 µg 89Zr-AMG 211 + 1,800 µg cold AMG 211. At 3 h the highest blood pool SUVmean was 4.0, and tracer serum half-life was 3.3 h. Uptake in CD3-rich lymphoid tissues such as the spleen and bone marrow was SUVmean 3.2 and 1.8, respectively. Uptake in these tissues decreased slower than in other normal tissues. 89Zr-AMG 211 remained intact in plasma and was excreted predominantly via the kidneys in degraded forms. Of 43 visible tumor lesions, 37 were PET quantifiable, with a SUVmax of 4.0 (interquartile range 2.7 – 4.4) at 3 h using the optimal imaging dose. The maximum tracer uptake differed between tumor lesions 5-fold within and 9-fold between patients. During AMG 211 treatment (n = 2) more tracer was present in the blood pool, while tumor lesions were not visualized, possibly reflecting target saturation.

Conclusions

In this first-in-human study high specific 89Zr-AMG 211 accumulation was observed in CD3-rich lymphoid tissues. In addition, a clear, inter- and intra-individual heterogeneous tumor uptake was seen.

Clinical trial identification

Legal entity responsible for the study

Elisabeth de Vries.

Funding

Amgen.

Editorial Acknowledgement

Not applicable.

Disclosure

F.V. Suurs: Research support: Amgen grant (insitution). J.A. Gietema: Research funding (institution): Roche Abbvie Siemens. E.G.E. de Vries: Research grant (institution): Amgen, Genentech, Roche, Chugai, Synthon, CytomX, Nordic Nanovector, Regeneron, G1 Therapeutics, AstraZeneca, Radius Health. Consulting (institution): Pfizer, Sanofi. All other authors have declared no conflicts of interest.

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