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Theranostic targeting of CAIX in patients with clear cell renal cell carcinoma: first‑in‑human safety, imaging and dosimetry findings with [68Ga]Ga‑DPI-4452

Presented at ASM 2024

Michael S. Hofman1,2, Ben Tran1,2, Darren R. Feldman3, Anna Pokorska-Bocci4, Solen Pichereau4, Jonathan Wessen2, Mohammad B. Haskali1,2, Richard Sparks5, Olena Vlasyuk1,2, Ivana Galetic4

1 Peter MacCallum Cancer Center, 305 Grattan Street. Melbourne, Victoria 3000, Australia;
2 Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia;
3 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA;
4 Debiopharm International SA, Lausanne, Switzerland
5 CDE Dosimetry Services, Inc., Knoxville, TN USA

Background

Carbonic anhydrase IX (CAIX) and cancer

•The cell surface glycoprotein CAIX is overexpressed in ~97% of clear cell renal cell carcinoma (ccRCC) cases,1 often due to mutations in the Von Hippel-Lindau tumour suppressor gene2
•High levels of CAIX are linked to aggressive tumour behavior, including, treatment resistance and poor outcomes2–6
•High tumoural expression of CAIX but limited expression in healthy tissues3,7 make CAIX an attractive diagnostic and therapeutic target
•Antibody-based tumour imaging for CAIX expression using zirconium-89-labeled girentuximab (an anti-CAIX antibody) allows tumour visualisation in 3–7 days post-administration8,9

DPI-4452

•DPI-4452 is a first-in-class, DOTA cage-containing, cyclic peptide with high-affinity binding to CAIX3
•Radiolabeling DPI-4452 with gallium-68 ([68Ga]Ga-DPI-4452) or lutetium-177 ([177Lu]Lu-DPI-4452) is an innovative and theranostic approach for identifying and treating patients with CAIX-expressing tumours3
•Radiolabeled DPI-4452 may confer better characteristics for both imaging and therapy compared with existing antibody approaches10

Sources

  1. Leibovich BC, et al. J Clin Oncol. 2007;25:4757–4767.
  2. Stillebroer AB, et al. Eur Urol. 2010;58:75–83.
  3. Massiere F, et al. J Nuc Med. 2024;65:761–767.
  4. Pastorekova S & Gillies RJ. Cancer Metastasis Rev. 2019;38:65–77.
  5. van Kuijk SJA, et al. Front Oncol. 2016;6:69.
  6. Pastorekova S, et al. Gastroenterology. 1997;112:398–408.
  7. Ilie M, et al. Br J Cancer. 2010;102:1627–1635.
  8. Shuch BM, et al. J Clin Oncol. 2023;41:LBA602-LBA602.
  9. Verhoeff SR, et al. Eur J Nucl Med Mol Imaging. 2019;46:1931-1939.
  10. Hofman MS, et al. J Nuc Med. 2024;65:740–743.