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

Official title

A Confirmatory, Open-label, Single-arm, Multi-centre Study to Evaluate Safety, Tolerability and Diagnostic Performance of 89Zirconium-labelled Girentuximab (89Zr-TLX250) to Non-invasively Detect Clear Cell Renal Cell Carcinoma (ccRCC) by Positron Emission Tomography/Computed Tomography (PET/CT) Imaging in Chinese Patients With Indeterminate Renal Masses (ZIRCON-CP Study)

Overview

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.

Interventions

• Drug 89Zr-TLX250 PET/CT
  89Zr-TLX250, is a chimeric monoclonal antibody (INN name: girentuximab) with specificity for the CAIX (carbonic anhydrase 9) antigen, radiolabelled with the positron emitting radiometal zirconium- 89. Girentuximab has a CAS number of 916138-87-9. The chemical formula, without the 89Zr and the desferrioxamine, is C6460H1006N1718O2018S48 with a molecular mass of 146.5 kg/mol. 89Zr-TLX250 is formulated as a solution for IV administration in glass vials at the nominal dosage strength of 37 MBq (±10

Primary outcome measures

• 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 [Time frame: 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]

Secondary outcome measures (5)

• To determine the 89Zr-TLX250's test performance [Time frame: Day of Imaging (Day 5±2 post- IP administration).]
• To determine the 89Zr-TLX250's test performance [Time frame: 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).]
• To determine the 89Zr-TLX250's test performance [Time frame: 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).]
• To assess the safety and tolerability of 89Zr-TLX250 [Time frame: 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)]
• To evaluate the impact of 89Zr-TLX250 PET/CT on clinical decision-making as a diagnostic tool [Time frame: 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).]

Eligibility criteria

Inclusion criteria

• Written and voluntarily given informed consent.
• Mainland Chinese male or female, aged ≥ 18 years.
• 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.
• Scheduled for lesion resection as part of regular diagnostic work-up within 90 days from planned IV 89Zr-TLX250 administration.
• 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.
• Sufficient life expectancy to justify nephrectomy.
• Consent to practise highly effective contraception until a minimum of 42 days after IV 89Zr-TLX250 administration.

Exclusion criteria

• A biopsy procedure only (rather than partial or total nephrectomy) is planned for histological species delineation of IRM.
• Renal mass known to be a metastasis of another primary tumour.
• Active non-renal malignancy requiring therapy during the time frame of the study participation.
• Multiple unilateral or bilateral IRM.
• 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).
• Planned antineoplastic therapies (for the period between IV administration of 89Zr-TLX250 and imaging).
• Exposure to murine or chimeric antibodies within the last 5 years.
• Previous administration of any radionuclide within 10 half-lives of the same.
• 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.
• Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
• 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.
• Women who are pregnant or breastfeeding.
• Known hypersensitivity to girentuximab or desferoxamine (DFO).
• Renal insufficiency with glomerular filtration rate (GFR) ≤ 45 mL/min/1.73 m².
• Vulnerable patients (e.g., being in detention).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

China · 8 centers

• Beijing Cancer Hospital — Beijing
• Zhejiang Provincial People's Hospital — Hangzhou
• Union Hospital Tongji Medical College Huazhong University Of Science And Technology — Hubei
• Zhongshan Hospital, Fudan University — Shanghai
• The First Affiliated Hospital of Soochow University — Suzhou
• Tianjin Cancer Hospital Airport Hospital — Tianjin
• Affiliated Hospital Of Jiangnan University — Wuxi
• Zhejiang Cancer Hospital — Zhejiang

Publications

• Shuch B, Pantuck AJ, Bernhard JC, Morris MA, Master V, Scott AM, van Praet C, Bailly C, Onal B, Aksoy T, Merkx R, Schuster DM, Lee ST, Pandit-Taskar N, Fan AC, Allman P, Schmidt K, Tauchmanova L, Wheatcroft M, Behrenbruch C, Hayward CRW, Mulders P. [89Zr]Zr-girentuximab for PET-CT imaging of clear-cell renal cell carcinoma: a prospective, open-label, multicentre, phase 3 trial. Lancet Oncol. 2024 PMID 39270701
• 2010 年第 7 版肾癌新分期的应用效果评估
• 肾包膜侵犯状况对于 肾癌临床症状及分期的意义
• ZIRDOSE. An open-label, Phase I study to assess safety, tolerability, radiation dosimetry, and imaging properties of 89Zr-labelled girentuximab (89Zr-girentuximab) for in vivo detection of clear cell renal carcinoma (CCRC) by positron emission tomography (PET) using different PET imaging methodologies. ClinicalTrials.gov: NCT03556046
• ZIRDAC-JP. Phase 1 open-label study to evaluate the safety/tolerability/radioactivity distribution of positron emission tomography (PET/CT) imaging with 89Zr-girentuximab (89Zr-TLX250) as well as to investigate its pharmacokinetics and pharmacodynamics in subjects with renal cell carcinoma including clear cell renal cell carcinoma (ZIRDAC-JP). ClinicalTrials.gov : NCT04496089
• ZIRCON. A confirmatory, prospective, open-label, multi-centre phase 3 study to evaluate diagnostic performance of 89Zirconium-labelled girentuximab(89Zr-TLX250) to non-invasively detect clear cell renal cell carcinoma (ccRCC) by positron emission tomography/CT (PET/CT) imaging in patients with indeterminate renal masses (ZIRCON study). ClinicalTrials.gov: NCT03849118
• Wang HY, Ding HJ, Chen JH, Chao CH, Lu YY, Lin WY, Kao CH. Meta-analysis of the diagnostic performance of [18F]FDG-PET and PET/CT in renal cell carcinoma. Cancer Imaging. 2012 Oct 26;12(3):464-74. doi: 10.1102/1470-7330.2012.0042. PMID 23108238
• van Asselt SJ, Oosting SF, Brouwers AH, Bongaerts AH, de Jong JR, Lub-de Hooge MN, Oude Munnink TH, Fiebrich HB, Sluiter WJ, Links TP, Walenkamp AM, de Vries EG. Everolimus Reduces (89)Zr-Bevacizumab Tumor Uptake in Patients with Neuroendocrine Tumors. J Nucl Med. 2014 Jul;55(7):1087-92. doi: 10.2967/jnumed.113.129056. Epub 2014 May 1. PMID 24790218

Identifiers

NCT: NCT06750419 · TLX250CDx-CP-002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗