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 Journal Article

   

Authors:	Pandit-Taskar, N.; O'Donoghue, J. A.; Chetty, D.; Max, S.; Wanik, D.; Ilovich, O.; Russell, M.; Nyima, T.; Divgi, C. R.; Yu, M.; Morris, M. J.
Article Title:	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
Abstract:	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 111In-radiolabeled anti-hK2 monoclonal antibody, [111In]-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 [111In]-DOTA-h11B6 (185 MBq of 111In), with or without 8 mg of unlabeled h11B6 to assess antibody mass effects. Sequential imaging and serial blood samples were collected to determine [111In]-DOTA-h11B6 biodistribution, dosimetry, serum radioactivity, and pharmacokinetics. Safety was assessed within a 2-wk follow-up period from the time of [111In]-DOTA-h11B6 administration. Results: Twenty-two participants received [111In]-DOTA-h11B6 and are included in this analysis. Within 6–8 d of administration, [111In]-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. ß 2024 by the Society of Nuclear Medicine and Molecular Imaging.
Keywords:	aged; middle aged; radiopharmaceuticals; metastasis; radiotherapy; diagnostic imaging; monoclonal antibody; antibodies, monoclonal; indium radioisotopes; chemistry; isotope labeling; tissue distribution; neoplasm metastasis; radiopharmaceutical agent; castration resistant prostate cancer; tissue kallikrein; tissue kallikreins; single heterocyclic rings; heterocyclic compounds, 1-ring; indium; hk2; humans; human; male; prostatic neoplasms, castration-resistant; mcrpc; h11b6; klk2
Journal Title:	Journal of Nuclear Medicine
Volume:	65
Issue:	7
ISSN:	0161-5505
Publisher:	Society of Nuclear Medicine
Date Published:	2024-07-01
Start Page:	1051
End Page:	1056
Language:	English
DOI:	10.2967/jnumed.124.267416
PUBMED:	38782459
PROVIDER:	scopus
PMCID:	PMC11218722
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85198026618&doi=10.2967%2fjnumed.124.267416&partnerID=40&md5=81860c78fe28947490331cd8efd7225a
Notes:	Article -- MSK corresponding author is Michael Morris -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/217523