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

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)

Timeline

Start

2024-11-06

Primary completion

2026-06-30

Completion

2026-06-30

Publications

• Background 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 Oct;25(10):1277-1287. doi: 10.1016/S1470-2045(24)00402-9. Epub 2024 Sep 10.
• Background 2010 年第 7 版肾癌新分期的应用效果评估
• Background 肾包膜侵犯状况对于 肾癌临床症状及分期的意义
• Background 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
• Background 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
• Background 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
• Background 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.
• Background 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.
• Background US FDA Guidance for Industry: Multiple Endpoints in Clinical Trials January 2017 (draft) https://www.fda.gov/media/102657/download
• Background Stillebroer AB, Franssen GM, Mulders PF, Oyen WJ, van Dongen GA, Laverman P, Oosterwijk E, Boerman OC. ImmunoPET imaging of renal cell carcinoma with (124)I- and (89)Zr-labeled anti-CAIX monoclonal antibody cG250 in mice. Cancer Biother Radiopharm. 2013 Sep;28(7):510-5. doi: 10.1089/cbr.2013.1487. Epub 2013 May 22.
• Background Stillebroer AB, Boerman OC, Desar IM, Boers-Sonderen MJ, van Herpen CM, Langenhuijsen JF, Smith-Jones PM, Oosterwijk E, Oyen WJ, Mulders PF. Phase 1 radioimmunotherapy study with lutetium 177-labeled anti-carbonic anhydrase IX monoclonal antibody girentuximab in patients with advanced renal cell carcinoma. Eur Urol. 2013 Sep;64(3):478-85. doi: 10.1016/j.eururo.2012.08.024. Epub 2012 Aug 21.
• Background Steffens MG, Boerman OC, de Mulder PH, Oyen WJ, Buijs WC, Witjes JA, van den Broek WJ, Oosterwijk-Wakka JC, Debruyne FM, Corstens FH, Oosterwijk E. Phase I radioimmunotherapy of metastatic renal cell carcinoma with 131I-labeled chimeric monoclonal antibody G250. Clin Cancer Res. 1999 Oct;5(10 Suppl):3268s-3274s.
• Background Steffens MG, Kranenborg MH, Boerman OC, Zegwaart-Hagemeier NE, Debruyne FM, Corstens FH, Oosterwijk E. Tumor retention of 186Re-MAG3, 111In-DTPA and 125I labeled monoclonal antibody G250 in nude mice with renal cell carcinoma xenografts. Cancer Biother Radiopharm. 1998 Apr;13(2):133-9. doi: 10.1089/cbr.1998.13.133.
• Background Steffens MG, Boerman OC, Oosterwijk-Wakka JC, Oosterhof GO, Witjes JA, Koenders EB, Oyen WJ, Buijs WC, Debruyne FM, Corstens FH, Oosterwijk E. Targeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal antibody G250. J Clin Oncol. 1997 Apr;15(4):1529-37. doi: 10.1200/JCO.1997.15.4.1529.
• Background Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med. 2005 Jun;46(6):1023-7.
• Background Snyder ME, Bach A, Kattan MW, Raj GV, Reuter VE, Russo P. Incidence of benign lesions for clinically localized renal masses smaller than 7 cm in radiological diameter: influence of sex. J Urol. 2006 Dec;176(6 Pt 1):2391-5; discussion 2395-6. doi: 10.1016/j.juro.2006.08.013.
• Background Smith-Bindman R, Lipson J, Marcus R, Kim KP, Mahesh M, Gould R, Berrington de Gonzalez A, Miglioretti DL. Radiation dose associated with common computed tomography examinations and the associated lifetime attributable risk of cancer. Arch Intern Med. 2009 Dec 14;169(22):2078-86. doi: 10.1001/archinternmed.2009.427.
• Background Schachter LR, Cookson MS, Chang SS, Smith JA Jr, Dietrich MS, Jayaram G, Herrell SD. Second prize: frequency of benign renal cortical tumors and histologic subtypes based on size in a contemporary series: what to tell our patients. J Endourol. 2007 Aug;21(8):819-23. doi: 10.1089/end.2006.9937.
• Background Rizvi SN, Visser OJ, Vosjan MJ, van Lingen A, Hoekstra OS, Zijlstra JM, Huijgens PC, van Dongen GA, Lubberink M. Biodistribution, radiation dosimetry and scouting of 90Y-ibritumomab tiuxetan therapy in patients with relapsed B-cell non-Hodgkin's lymphoma using 89Zr-ibritumomab tiuxetan and PET. Eur J Nucl Med Mol Imaging. 2012 Mar;39(3):512-20. doi: 10.1007/s00259-011-2008-5. Epub 2012 Jan 5.
• Background Oosting SF, Brouwers AH, van Es SC, Nagengast WB, Oude Munnink TH, Lub-de Hooge MN, Hollema H, de Jong JR, de Jong IJ, de Haas S, Scherer SJ, Sluiter WJ, Dierckx RA, Bongaerts AH, Gietema JA, de Vries EG. 89Zr-bevacizumab PET visualizes heterogeneous tracer accumulation in tumor lesions of renal cell carcinoma patients and differential effects of antiangiogenic treatment. J Nucl Med. 2015 Jan;56(1):63-9. doi: 10.2967/jnumed.114.144840. Epub 2014 Dec 4.
• Background Oosterwijk E, Divgi CR, Brouwers A, Boerman OC, Larson SM, Mulders P, Old LJ. Monoclonal antibody-based therapy for renal cell carcinoma. Urol Clin North Am. 2003 Aug;30(3):623-31. doi: 10.1016/s0094-0143(03)00028-4.
• Background Oosterwijk E, Ruiter DJ, Hoedemaeker PJ, Pauwels EK, Jonas U, Zwartendijk J, Warnaar SO. Monoclonal antibody G 250 recognizes a determinant present in renal-cell carcinoma and absent from normal kidney. Int J Cancer. 1986 Oct 15;38(4):489-94. doi: 10.1002/ijc.2910380406.
• Background Muselaers CH, Stillebroer AB, Desar IM, Boers-Sonderen MJ, van Herpen CM, de Weijert MC, Langenhuijsen JF, Oosterwijk E, Leenders WP, Boerman OC, Mulders PF, Oyen WJ. Tyrosine kinase inhibitor sorafenib decreases 111In-girentuximab uptake in patients with clear cell renal cell carcinoma. J Nucl Med. 2014 Feb;55(2):242-7. doi: 10.2967/jnumed.113.131110. Epub 2014 Jan 6.
• Background Muselaers CH, Boerman OC, Oosterwijk E, Langenhuijsen JF, Oyen WJ, Mulders PF. Indium-111-labeled girentuximab immunoSPECT as a diagnostic tool in clear cell renal cell carcinoma. Eur Urol. 2013 Jun;63(6):1101-6. doi: 10.1016/j.eururo.2013.02.022. Epub 2013 Feb 21.
• Background Muselaers S, Mulders P, Oosterwijk E, Oyen W, Boerman O. Molecular imaging and carbonic anhydrase IX-targeted radioimmunotherapy in clear cell renal cell carcinoma. Immunotherapy. 2013 May;5(5):489-95. doi: 10.2217/imt.13.36.
• Background Lowrance WT, Yee DS, Savage C, Cronin AM, O'Brien MF, Donat SM, Vickers A, Russo P. Complications after radical and partial nephrectomy as a function of age. J Urol. 2010 May;183(5):1725-30. doi: 10.1016/j.juro.2009.12.101. Epub 2010 Mar 17.
• Background Loh A, Sgouros G, O'Donoghue JA, Deland D, Puri D, Capitelli P, Humm JL, Larson SM, Old LJ, Divgi CR. Pharmacokinetic model of iodine-131-G250 antibody in renal cell carcinoma patients. J Nucl Med. 1998 Mar;39(3):484-9.
• Background Kutikov A, Fossett LK, Ramchandani P, Tomaszewski JE, Siegelman ES, Banner MP, Van Arsdalen KN, Wein AJ, Malkowicz SB. Incidence of benign pathologic findings at partial nephrectomy for solitary renal mass presumed to be renal cell carcinoma on preoperative imaging. Urology. 2006 Oct;68(4):737-40. doi: 10.1016/j.urology.2006.04.011.
• Background The 2007 Recommendations of the International Commission on Radiological Protection. ICRP publication 103. Ann ICRP. 2007;37(2-4):1-332. doi: 10.1016/j.icrp.2007.10.003.
• Background Hekman MCH, Rijpkema M, Aarntzen EH, Mulder SF, Langenhuijsen JF, Oosterwijk E, Boerman OC, Oyen WJG, Mulders PFA. Positron Emission Tomography/Computed Tomography with 89Zr-girentuximab Can Aid in Diagnostic Dilemmas of Clear Cell Renal Cell Carcinoma Suspicion. Eur Urol. 2018 Sep;74(3):257-260. doi: 10.1016/j.eururo.2018.04.026. Epub 2018 May 3.
• Background Guo J, Ma J, Sun Y, Qin S, Ye D, Zhou F, He Z, Sheng X, Bi F, Cao D, Chen Y, Huang Y, Liang H, Liang J, Liu J, Liu W, Pan Y, Shu Y, Song X, Wang W, Wang X, Wu X, Xie X, Yao X, Yu S, Zhang Y, Zhou A; written; CSCO Renal Cell Carcinoma Committee. Chinese guidelines on the management of renal cell carcinoma (2015 edition). Ann Transl Med. 2015 Nov;3(19):279. doi: 10.3978/j.issn.2305-5839.2015.11.21. No abstract available.
• Background Gaykema SB, Brouwers AH, Lub-de Hooge MN, Pleijhuis RG, Timmer-Bosscha H, Pot L, van Dam GM, van der Meulen SB, de Jong JR, Bart J, de Vries J, Jansen L, de Vries EG, Schroder CP. 89Zr-bevacizumab PET imaging in primary breast cancer. J Nucl Med. 2013 Jul;54(7):1014-8. doi: 10.2967/jnumed.112.117218. Epub 2013 May 7.
• Background Divgi CR, Uzzo RG, Gatsonis C, Bartz R, Treutner S, Yu JQ, Chen D, Carrasquillo JA, Larson S, Bevan P, Russo P. Positron emission tomography/computed tomography identification of clear cell renal cell carcinoma: results from the REDECT trial. J Clin Oncol. 2013 Jan 10;31(2):187-94. doi: 10.1200/JCO.2011.41.2445. Epub 2012 Dec 3.
• Background Divgi CR, Pandit-Taskar N, Jungbluth AA, Reuter VE, Gonen M, Ruan S, Pierre C, Nagel A, Pryma DA, Humm J, Larson SM, Old LJ, Russo P. Preoperative characterisation of clear-cell renal carcinoma using iodine-124-labelled antibody chimeric G250 (124I-cG250) and PET in patients with renal masses: a phase I trial. Lancet Oncol. 2007 Apr;8(4):304-10. doi: 10.1016/S1470-2045(07)70044-X.
• Background Divgi CR, O'Donoghue JA, Welt S, O'Neel J, Finn R, Motzer RJ, Jungbluth A, Hoffman E, Ritter G, Larson SM, Old LJ. Phase I clinical trial with fractionated radioimmunotherapy using 131I-labeled chimeric G250 in metastatic renal cancer. J Nucl Med. 2004 Aug;45(8):1412-21.
• Background Divgi CR, Bander NH, Scott AM, O'Donoghue JA, Sgouros G, Welt S, Finn RD, Morrissey F, Capitelli P, Williams JM, Deland D, Nakhre A, Oosterwijk E, Gulec S, Graham MC, Larson SM, Old LJ. Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma. Clin Cancer Res. 1998 Nov;4(11):2729-39.
• Background Dijkers EC, Oude Munnink TH, Kosterink JG, Brouwers AH, Jager PL, de Jong JR, van Dongen GA, Schroder CP, Lub-de Hooge MN, de Vries EG. Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin Pharmacol Ther. 2010 May;87(5):586-92. doi: 10.1038/clpt.2010.12. Epub 2010 Mar 31.
• Background Cheal SM, Punzalan B, Doran MG, Evans MJ, Osborne JR, Lewis JS, Zanzonico P, Larson SM. Pairwise comparison of 89Zr- and 124I-labeled cG250 based on positron emission tomography imaging and nonlinear immunokinetic modeling: in vivo carbonic anhydrase IX receptor binding and internalization in mouse xenografts of clear-cell renal cell carcinoma. Eur J Nucl Med Mol Imaging. 2014 May;41(5):985-94. doi: 10.1007/s00259-013-2679-1. Epub 2014 Mar 7.
• Background Brouwers AH, Buijs WC, Mulders PF, de Mulder PH, van den Broek WJ, Mala C, Oosterwijk E, Boerman OC, Corstens FH, Oyen WJ. Radioimmunotherapy with [131I]cG250 in patients with metastasized renal cell cancer: dosimetric analysis and immunologic response. Clin Cancer Res. 2005 Oct 1;11(19 Pt 2):7178s-7186s. doi: 10.1158/1078-0432.CCR-1004-0010.
• Background Brouwers AH, van Eerd JE, Frielink C, Oosterwijk E, Oyen WJ, Corstens FH, Boerman OC. Optimization of radioimmunotherapy of renal cell carcinoma: labeling of monoclonal antibody cG250 with 131I, 90Y, 177Lu, or 186Re. J Nucl Med. 2004 Feb;45(2):327-37.
• Background Brouwers AH, Buijs WC, Oosterwijk E, Boerman OC, Mala C, De Mulder PH, Corstens FH, Mulders PF, Oyen WJ. Targeting of metastatic renal cell carcinoma with the chimeric monoclonal antibody G250 labeled with (131)I or (111)In: an intrapatient comparison. Clin Cancer Res. 2003 Sep 1;9(10 Pt 2):3953S-60S.
• Background Brouwers AH, Dorr U, Lang O, Boerman OC, Oyen WJ, Steffens MG, Oosterwijk E, Mergenthaler HG, Bihl H, Corstens FH. 131 I-cG250 monoclonal antibody immunoscintigraphy versus [18 F]FDG-PET imaging in patients with metastatic renal cell carcinoma: a comparative study. Nucl Med Commun. 2002 Mar;23(3):229-36. doi: 10.1097/00006231-200203000-00005.
• Background Borjesson PK, Jauw YW, de Bree R, Roos JC, Castelijns JA, Leemans CR, van Dongen GA, Boellaard R. Radiation dosimetry of 89Zr-labeled chimeric monoclonal antibody U36 as used for immuno-PET in head and neck cancer patients. J Nucl Med. 2009 Nov;50(11):1828-36. doi: 10.2967/jnumed.109.065862. Epub 2009 Oct 16.
• Background Andersson M, Johansson L, Eckerman K, Mattsson S. IDAC-Dose 2.1, an internal dosimetry program for diagnostic nuclear medicine based on the ICRP adult reference voxel phantoms. EJNMMI Res. 2017 Nov 3;7(1):88. doi: 10.1186/s13550-017-0339-3.

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