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

Phase 3

Recruiting

• Conditions: Clear Cell Renal Cell Carcinoma
• Interventions: Drug: 89Zr-TLX250 PET/CT

• Registration Number: NCT06750419
• Lead Sponsor: Telix Pharmaceuticals (Innovations) Pty Limited

Brief Summary

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)

Detailed Description

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.

Study Timeline

• Study Start: 2024-11-06
• Study First Submitted: 2024-11-26
• Status Verified: 2024-12
• Study First Submitted QC: 2024-12-19
• Last Update Submitted: 2024-12-19
• Study First Posted: 2024-12-27
• Last Update Posted: 2024-12-27
• Primary Completion: 2026-06-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 82

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental arm receiving the IP	89Zr-TLX250 PET/CT	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. Following pre-screen morphological imaging to confirm evidence of IRM (to occur within 90 days of study enrolment), participants will attend a screening visit within 30 days of study enrolment, at which time baseline examinations will be undertaken. On Day 0, all successfully screened participants will undergo a slow IV administration of 89Zr- TLX250, at the nuclear medicine service of the respective study site. For all subjects, a PET/CT scan of the abdomen will occur on visit Day 5 (±2 days post administration \[p.a.\]) with nephrectomy to be performed any time after the PET/CT imaging visit, but no later than 90 days p.a. 89Zr-TLX250.

Primary Outcome Measures

Name	Time	Method
To evaluate the sensitivity and specificity of qualitative assessment of PET/CT imaging with 89Zr-TLX250 to non-invasively detect ccRCC in patients with indeterminate renal masses, using histology as standard of truth	From Visit 4 till end of study. Diagnostic PET/CT scan on Day 5±2 days post 89Zr-TLX250 administration. Histological confirmation of the material from nephrectomy conducted within 90 days post 89Zr-TLX250 administration served as standard of truth	Evaluating this outcome involved using a PET/CT machine on all patients to determine the uptake of the Zr89 radiotracer within the renal lesion, which was then compared to the histological determination of the lesion type following resection

Secondary Outcome Measures

Name	Time	Method
To determine the 89Zr-TLX250's test performance	Day of Imaging (Day 5±2 post- IP administration), Post-Imaging study visit (Day 42±7 post- IP administration), Day of surgery (within 28 days post-IP administration) or Day of surgery (28 to 90 days post-IP administration).	Evaluate the diagnostic accuracy (%) of 89Zr-TLX250 PET/CT in distinguishing ccRCC from non-ccRCC in the kidney in the Chinese patient population.
To assess the safety and tolerability of 89Zr-TLX250	Day of IP administration (Day 0), Day of Imaging (Day 5±2 post- IP administration), Post-Imaging study visit (Day 42±7 post- IP administration), Day of surgery (within 28 days post-IP administration) or Day of surgery (28-90 days post-IP administration)	Number of AEs, incidence of anti-drug antibody detection following use of the study drug in Chinese patients with IRM
To evaluate the impact of 89Zr-TLX250 PET/CT on clinical decision-making as a diagnostic tool	Day of Imaging (Day 5±2 post- IP administration), Post-Imaging study visit (Day 42±7 post- IP administration), Day of surgery (within 28 days post-IP administration) or Day of surgery (28 to 90 days post-IP administration).	Proportion of participants with changes in management plans based on PET/CT scan findings versus conventional imaging following the use of 89Zr-TLX250

Trial Locations

Locations (8)

Beijing Cancer Hospital; 🇨🇳 Beijing, China

Zhejiang Provincial People's Hospital; 🇨🇳 Hangzhou, China

Union Hospital Tongji Medical College Huazhong University Of Science And Technology; 🇨🇳 Hubei, China

Zhongshan Hospital, Fudan University; 🇨🇳 Shanghai, China

The First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, China

Tianjin Cancer Hospital Airport Hospital; 🇨🇳 Tianjin, China

Affiliated Hospital Of Jiangnan University; 🇨🇳 Wuxi, China

Zhejiang Cancer Hospital; 🇨🇳 Zhejiang, China