89Zr-TLX250 for PET/CT Imaging of ccRCC - ZIRCON-CP Study

89Zr-TLX250 is under clinical development as a diagnostic agent targeting clear cell renal cell carcinoma, and this Phase 3 bridging study in mainland Chinese patients is intended to support the successful ZIRCON data (ZIRCON Clinicaltrial.gov ID: NCT03849118)

This will be a confirmatory, prospective, open-label, single-arm, multi-centre study in a Chinese patient population. The study is designed to evaluate the safety, tolerability, sensitivity and specificity of 89Zr-TLX250 Positron Emission Tomography/Computed Tomography (PET/CT) imaging to non-invasively detect Clear Cell Renal Cell Carcinoma (ccRCC). The multi-centre study will be conducted in mainland China in adult patients with Indeterminate Renal Masses (IRM), who are scheduled for partial or total nephrectomy as part of their standard of care.

Approximately 82 evaluable adult patients will be recruited from approximately 8 renal cancer care specialist centres with access to state-of-the-art PET/CT imaging in mainland China. The number of enrolled participants may be increased to ensure sufficient confidence in measuring sensitivity and specificity of 89Zr-TLX250 PET/CT imaging.

The study involves a single administration of 37 MBq (±10%) of 89Zr-TLX250, containing a mass dose of 10 mg of girentuximab, in mainland Chinese participants (ZIRCON-CP). This is consistent with the confirmatory, prospective, multinational clinical trial ZIRCON (ClinicalTrials.gov ID: NCT03849118). This study consists of seven visits. Imaging will then be conducted 5±2 days post administration. The partial/total nephrectomy will then 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.

On Day 5±2 post study drug administration, an abdominal PET/CT imaging will be obtained. In patients, in which unexpected evidence for disseminated disease is observed, PET/CT imaging may be extended to complete whole body imaging(vertex of skull to toe) at the discretion of the investigator.

Image data analyses will be performed by a central imaging vendor.

For participants who were nephrectomised within 28 days post administration, the final study visit will be conducted on Day 42 (±7 days). For participants with nephrectomy between 28 and 90 days post administration, the final study visit will be performed 35 days (±7 days) after surgery.

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 Magnetic Resonance Imaging \[MRI\]), 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.

The duration of this study is expected to be about 12 months, with a follow-up of 4 months. The study duration for a single participant will be approximately between 4 - 6 months.

No interim analysis is planned for this study.

Eligibility Criteria:
Inclusion Criteria:

1. Written and voluntarily given informed consent.
2. Mainland Chinese male or female, aged ≥ 18 years.
3. Imaging evidence of a single IRM of ≤ 7 cm in largest diameter (tumour stage cT1), on SoC imaging based on national standards, not older than 90 days on Day 0, but performed before any screening procedure.
4. Scheduled for lesion resection as part of regular diagnostic work-up within 90 days from planned IV 89Zr-TLX250 administration.
5. Negative serum pregnancy tests in female patients of childbearing potential at screening. Confirmation of negative pregnancy test result from urine within 24 hours prior to receiving investigational product.
6. Sufficient life expectancy to justify nephrectomy.
7. Consent to practise highly effective contraception until a minimum of 42 days after IV 89Zr-TLX250 administration.

Exclusion Criteria:

1. A biopsy procedure only (rather than partial or total nephrectomy) is planned for histological species delineation of IRM.
2. Renal mass known to be a metastasis of another primary tumour.
3. Active non-renal malignancy requiring therapy during the time frame of the study participation.
4. Multiple unilateral or bilateral IRM.
5. Chemotherapy, radiotherapy, targeted therapy or immunotherapy within 4 weeks prior to the planned administration of 89Zr -TLX250 or continuing adverse effects (\> grade 1) from such therapy (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0).
6. Planned antineoplastic therapies (for the period between IV administration of 89Zr-TLX250 and imaging).
7. Exposure to murine or chimeric antibodies within the last 5 years.
8. Previous administration of any radionuclide within 10 half-lives of the same.
9. Serious non-malignant disease (e.g. psychiatric, infectious, autoimmune or metabolic), that may interfere with the objectives of the study or with the safety or compliance of the study subject, as judged by the investigator.
10. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
11. Exposure to any experimental diagnostic or therapeutic drug within 4 weeks or 5 half-lives (whichever is longer) from the date of planned administration of 89Zr-TLX250.
12. Women who are pregnant or breastfeeding.
13. Known hypersensitivity to girentuximab or desferoxamine (DFO).
14. Renal insufficiency with glomerular filtration rate (GFR) ≤ 45 mL/min/1.73 m².
15. Vulnerable patients (e.g., being in detention).