First-in-human clinical trial design of a first-in-class theranostic approach with a peptide-based radioligand targeting CAIX-expressing tumors

Presented at the 2023 ASCO Annual Meeting

Darren R Feldman1, Ben Tran2, Michael Hofman2, Louise Emmett3, Pierre Olivier4, Hakim Mahammedi5, Ivana Galetic6, Anna Pokorska-Bocci6, FlorileneBouisset6, Kathrin Gollmer6*, Mariya Pavlyuk6,LibuseTauchmanova6*, Ken Herrmann7

1 Department of Medicine, Memorial Sloan Kettering Cancer Center, NY, USA and Department of Medicine, Weill Cornell Medical College, NY, USA
2Peter MacCallum Cancer Center, Melbourne, Australia
3StVincent’s Hospital, Sydney, Australia
4CHRU de Nancy -Hopitauxde Brabois,Nancy, France
5Département of Medical Oncology, France; Centre Jean Perrin, Clermont-Ferrand, France
6Debiopharm, Lausanne, Switzerland
7University Hospital Essen, Essen, Germany
*KG and LT were employed at Debiopharm at the time the study was designed


Expression of carbonic anhydrase IX (CA IX), a cell surface glycoprotein, can be induced by a state of hypoxia or by mutation of the Von Hippel-Lindau tumor suppressor gene. CA IX expression in tumors is often associated with progressive disease and overall poor outcomes in various solid cancers. Notably, high CA IX expression has been observed in 83%, 40%, and 29% of clear cell renal cell carcinoma (ccRCC), pancreatic ductal adenocarcinoma (PDAC), and colorectal cancer (CRC) specimens, respectively1. CA IX may therefore represent a valuable therapeutic target. DPI-4452 is a first-in-class cyclic peptide that binds with high affinity to CA IX. Radiolabeling DPI-4452 with gallium-68 ([68Ga]Ga-DPI-4452) or lutetium-177 ([177Lu]Lu-DPI-4452) is an innovative theranostic approach for identifying and treating patients (pts) with CA IX-expressing tumors. Pre-clinical data has shown that [177Lu]Lu-DPI-4452 is taken up by tumors and induces dose-dependent growth inhibition in ccRCC and CRC xenograft mouse models1,2.