Evaluation of [89Zr]Zr-girentuximab PET imaging of clear cell renal cell carcinoma in Chinese patients: a Phase 1 clinical study (ZIRDOSE-CP)

Results from a multinational Phase 3 study demonstrated high accuracy and a favorable safety and tolerability profile of [89Zr]Zr-girentuximab PET for detection and characterization of clear cell renal cell carcinoma (ccRCC). However, [89Zr]Zr-girentuximab has not been studied in Chinese patients. In this Phase 1 study, we aimed to evaluate safety and tolerability, radiation and tumor dosimetry, and pharmacokinetics of [89Zr]Zr-girentuximab PET in Chinese patients with suspected ccRCC. This study was approved by the Ethics Committee of Beijing Cancer Hospital (2022YW225) and was conducted in accordance with the Declaration of Helsinki. All patients provided written informed consent. Ten Chinese patients received 37 MBq (± 10%; 10mg mass dose) of [89Zr]Zr-girentuximab intravenously. Whole-body PET imaging was performed in the supine position at approximately 0.5, 4, 24, 72 hours, and 7 ± 1 days after administration, and low dose CT was used for attenuation correction. Adverse events were recorded from time of [89Zr]Zr-girentuximab administration through final visit. Blood samples were collected from patients approximately 1 hour before, and 0.5, 1, 2, 4, 24, 72 hours, and 5 ± 1 days after [89Zr]Zr-girentuximab administration. Biodistribution and normal organ dosimetry were performed based on PET images to determine significant differences in tumor-absorbed dose. Of 10 adverse events reported, none were serious or considered related to [89Zr]Zr-girentuximab. The organs receiving the highest mean (SD) normalized absorbed doses were the liver (1.51 [0.23] mGy/MBq), kidneys (1.42 [0.35] mGy/MBq), and heart wall (1.22 [0.18] mGy/MBq), with a mean whole-body normalized effective dose of 0.49 (0.08) mSv/MBq. In 7 patients with histologically confirmed ccRCC, mean (SD) tumor normalized absorbed dose was 2.87 (1.54) mGy/MBq (range: 1.17 to 5.41 mGy/MBq). [89Zr]Zr-girentuximab has a favorable safety and tolerability profile in Chinese patients, with a dosimetry profile similar to previously studied non-Chinese populations. [89Zr]Zr-girentuximab is a promising novel PET agent for the detection and characterization of ccRCC in Chinese patients. Trial registration: ClinicalTrials.gov Identifier NCT05861778. Registered 17 May 2023.