89Zr-DFO-girentuximab for PET imaging of solid tumors likely to express high levels of carbonic anhydrase IX.
Authors: Iagaru Andrei , Takalkar Amol Madan , Higgins Geoffrey Stuart , Kiser Jackson William , Tauchmanova Libuse , Shah Sapna , Vadali Kavita , Hayward Colin , Crowley James Robert 
Published: March 2023

TPS738 Background: Carbonic anhydrase IX (CAIX) is a cell surface antigen that is widely expressed in many cancers including clear cell renal cell carcinoma, urothelial and triple negative breast cancers, and thus is a potential target for imaging and therapy. 89Zr-DFO-girentuximab (hereafter referred to as TLX250-CDx) is a diagnostic radiopharmaceutical for PET imaging that targets CAIX and has demonstrated clinical success in ccRCC imaging. Genitourinary (GU) cancer types that express CAIX lack robust diagnostic and management options. To improve the morbidity and mortality, diagnostic and therapeutic innovation is needed; theranostics with TLX250-CDx may play an integral role. Moreover, TLX250-CDx could assist with patient selection for immuno-oncology therapy as CAIX tumoral expression is associated with resistance to immunotherapy. Finally, TLX250-CDx imaging could provide a cost-effective method for monitoring response to various therapies. In this pilot study, patients with different tumor types likely to express CAIX that lack effective therapies will be evaluated for TLX250-CDx tumor uptake. Methods: This is an open-label, non-randomized study to evaluate feasibility of targeting CAIX for potential diagnostic and therapeutic applications. Data gathered from this pilot study will support a larger trial with patients with the tumor types expressing the greatest avidity forTLX250-CDx, as well as therapeutic studies targeting CAIX. The study's primary objective is to noninvasively evaluate TLX250-CDx PET/CT imaging of CAIX tumoral expression in different solid tumors. The secondary objective is to evaluate tolerability and safety of TLX250-CDx administration in patients with different tumor types. Patients with cancer types including cervical and ovarian (minimum 5 patients per type) will be enrolled. Patients must have at least one non-central nervous system measurable target lesion (as per RECIST 1.1) documented by conventional imaging performed within 30 days before dosing. Patients will receive a single administration of TLX250-CDx (37 MBq [1mCi] ± 10%, containing 10 mg of girentuximab), and will undergo PET/CT imaging 5 ± 2 days later. Tumor uptake of TLX250-CDx will be assessed per lesion, up to the 10 most active lesions. Qualitative visual analysis (presence or absence of localized uptake associated with tumor, as seen on contrast-enhanced CT, MRI and/or FDG PET/CT), will be used to evaluate concordance of tumor lesion detection between TLX250-CDx PET/CT and conventional imaging according to RECIST 1.1. Patient safety will be evaluated based on incidence and nature of adverse events and clinically significant changes in laboratory test values, vital signs, or physical exam. Statistics will be descriptive with no formal hypothesis. The study is ongoing. Acknowledgements: Stefanie D. Martina, MS (Telix Pharmaceuticals) provided writing/editorial support. Clinical trial information: NCT05563272 .