A Phase 0 Study to Assess the Biodistribution and Pharmacokinetics of a Radiolabeled Antibody Targeting Human Kallikrein 2 in Participants with Metastatic Castration-Resistant Prostate Cancer.
| Autor: | Pandit-Taskar N; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.; Department of Radiology, Weill Cornell Medical Center, New York, New York., O'Donoghue JA; Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York., Chetty D; Janssen Research & Development, LLC, Spring House, Pennsylvania., Max S; Janssen Research & Development, LLC, Spring House, Pennsylvania., Wanik D; Invicro, LLC, Boston, Massachusetts., Ilovich O; Invicro, LLC, Boston, Massachusetts., Russell M; Janssen Research & Development, LLC, Spring House, Pennsylvania., Nyima T; Memorial Sloan Kettering Cancer Center, New York, New York., Divgi CR; Janssen Research & Development, LLC, Spring House, Pennsylvania., Yu M; Janssen Research & Development, LLC, Spring House, Pennsylvania., Morris MJ; Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York; and morrism@mskcc.org.; Department of Medicine, Weill Cornell Medicine, New York, New York. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2024 Jul 01; Vol. 65 (7), pp. 1051-1056. Date of Electronic Publication: 2024 Jul 01. |
| DOI: | 10.2967/jnumed.124.267416 |
| Abstrakt: | Despite the inclusion of multiple agents within the prostate cancer treatment landscape, new treatment options are needed to address the unmet need for patients with metastatic castration-resistant prostate cancer (mCRPC). Although prostate-specific membrane antigen is the only cell-surface target to yield clinical benefit in men with advanced prostate cancer, additional targets may further advance targeted immune, cytotoxic, radiopharmaceutical, and other tumor-directed therapies for these patients. Human kallikrein 2 (hK2) is a novel prostate-specific target with little to no expression in nonprostate tissues. This first-in-human phase 0 trial uses an 111 In-radiolabeled anti-hK2 monoclonal antibody, [ 111 In]-DOTA-h11B6, to credential hK2 as a potential target for prostate cancer treatment. Methods: Participants with progressive mCRPC received a single infusion of 2 mg of [ 111 In]-DOTA-h11B6 (185 MBq of 111 In), with or without 8 mg of unlabeled h11B6 to assess antibody mass effects. Sequential imaging and serial blood samples were collected to determine [ 111 In]-DOTA-h11B6 biodistribution, dosimetry, serum radioactivity, and pharmacokinetics. Safety was assessed within a 2-wk follow-up period from the time of [ 111 In]-DOTA-h11B6 administration. Results: Twenty-two participants received [ 111 In]-DOTA-h11B6 and are included in this analysis. Within 6-8 d of administration, [ 111 In]-DOTA-h11B6 visibly accumulated in known mCRPC lesions, with limited uptake in other organs. Two treatment-emergent adverse events unrelated to treatment occurred, including tumor-related bleeding in 1 patient, which led to early study discontinuation. Serum clearance, biodistribution, and tumor targeting were independent of total antibody mass (2 or 10 mg). Conclusion: This first-in-human study demonstrates that tumor-associated hK2 can be identified and targeted using h11B6 as a platform as the h11B6 antibody selectively accumulated in mCRPC metastases with mass-independent clearance kinetics. These data support the feasibility of hK2 as a target for imaging and hK2-directed agents as potential therapies in patients with mCRPC. (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.) |
| Databáze: | MEDLINE |
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