89Zr-TLX250 is a carbonic anydrase IX (CAIX)-targeted imaging agent that is under clinical development as a non-invasive diagnostic imaging agent for teh detection of clear cell renal cell carcinoma (ccRCC). The Phase 1 study part of this study is to confirm the safety/tolerability and to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) in subjects with suspected renal cell carcinoma (RCC) including clear cell renal cell carcinoma. The Phase 2 component of the study is to to evaluate the sensitivity/specificity of using 89Zr-TLX250 PET/CT images to detect RCC and ccRCC in patients with suspected RCC.

Phase 1:

The phase 1 component of this study will be conducted in in 6-10 subjects at one study center, with the objective of confirming the safety/tolerability and the whole-body dose distribution of 89Zr-TLX250. 89Zr-TLX250 will be administered via a single IV injection (at least 3 min) at an activity dose of 37 MBq (± 10%) and at a dose of 10 mg (±10%). After the enrollment of 6 subjects, if the male-to-female ratio is different from the Japanese epidemiological RCC data (male-to-female ratio ≒ 2:1 in 2017), more subjects, up to 10 subjects in total, are to be enrolled.

Blood sampling for pharmacokinetic analysis will be is performed at 0.5, 1, 2, 4, 24, 72 h and during the Day 5 ± 2 imaging visit. The dose distribution will be determined using low-dose, non-contrast-enhanced CT whole body imaging at 0.5, 4, 24, 72 h and Day 5 ± 2. Diagnostic images will be acquired on Day 3 and Day 5 ± 2 using whole body PET/CT-imaging where individual organs will be assessed using Medical Internal Radiation Dose (MIRD) method.

Seven days after the Day 5 ± 2 imaging visit, patients will attend a follow-up visit to conduct safety evaluations and to undergo blood sampling for HACA measurement.

Phase 2:

The phase 2 component of this study will be conducted after the completion of the phase 1 study in 6-10 patients. This part of the study is equivalent to a phase 2, open-label, multi-center (2-5 sites) to assess the sensitivity/specificity of PET/CT images in subjects with suspected but not definitely diagnosed RCC including ccRCC. The study is intended to evaluate the sensitivity and specificity of PET/CT test as a non-invasive test with the CAIX-targeted imaging agent 89Zr-TLX250. The study will include patients who are scheduled to undergo a partial or total nephrectomy. Patients with an indeterminate renal mass with the longest diameter of 7cm or less, by diagnostic imaging, will receive a single administration of 37 MBq (+/- 10%) 89Zr-TLX250. Imaging will then be conducted Day 5 ± 2 post administration. The partial/total nephrectomy will be performed at institutional discretion any time following the PET/CT imaging visit, but no later than 90 days post administration of 89Zr-TLX250. Histological tumour samples will be prepared and used for histological diagnosis of the renal mass (ccRCC or non-ccRCC) read by a central laboratory.

Image data analyses will be performed by a central image core lab. Qualitative visual analysis (presence or absence of localised 89Zr-TLX250 uptake inside or in vicinity of renal lesion, as seen on contrast-enhanced CT or MRI), will be used to assess test performance or 89Zr-TLX-250 PET/CT imaging to non-invasively detect ccRCC, using histological results from the central histological reference laboratory as standard of truth.

Inclusion Criteria:

Phase 1:

1. Written and voluntarily given informed consent
2. Aged ≥20 years at the time of enrollment
3. Suspected renal cell carcinoma who have been diagnosed with a renal mass by CT or MRI performed within 90 days before screening
4. Sufficient life expectancy to participate in the study
5. Consent to practice barrier contraception (condoms) until a minimum of 42 days and 90 days after 89Zr-TLX250 administration in female and male, respectively

Phase 2 Part

1. Written and voluntarily given informed consent
2. Aged ≥20 years at the time of enrollment
3. Imaging evidence of a single indeterminate renal mass of ≤ 7 cm in largest diameter on CT or MRI within 90 days prior to screening
4. Scheduled for lesion resection as part of regular diagnostic work-up within 90 days from planned 89Zr-TLX250 administration
5. Sufficient life expectancy to undergo nephrectomy
6. Consent to practice barrier contraception (condoms) until a minimum of 42 days and 90 days after 89Zr-TLX250 administration in female and male, respectively

Exclusion Criteria:

Commonly applied for Phase 1 part and Phase 2 part

1. Those who have hypersensitivity to Girentuximab or DFO
2. Patients with metastatic renal tumor
3. Patients who need treatment for other active malignancies during the study period
4. Patients who have undergone chemotherapy, radiation therapy, or immunotherapy within 4 weeks before the administration of the investigational drug, or have continued adverse events of grade 1 (defined in NCI-CTCAE v5.0) or higher
5. Patients scheduled for anticancer drug treatment during the period from administration of investigational drug to image collection
6. Patients who have been exposed to mouse or chimeric antibody within the past 5 years
7. Patients who have been administered some kind of radionuclide earlier than 10 half-lives of the nuclide.
8. Patients with severe, but not fatal disease, for which the principal investigator / investigator has determined that study participation is not appropriate
9. Women who are pregnant or breastfeeding. And women with childbearing potential who are not pregnant or breastfeeding but suspected of being pregnant by the blood test at screening and pre-dose (within 24 hours before administration). Pre-dose blood pregnancy test can be replaced with urine test
10. Patients who have been administered the drug by any clinical study or clinical trial within 30 days before the scheduled administration of the investigational drug
11. Patients who cannot give legally valid consent by himself / herself
12. Patients with renal dysfunction whose GFR is 60mL / min / 1.73m2 or less
13. Patents who are socially vulnerable (e.g., patients in custody)
14. Others who are judged by the principal investigator or investigator to be inappropriate for participation in this trial Applied only to Phase 2 part 15． Patients whose biopsy is more suitable for pathological diagnosis than partial resection or nephrectomy