A phase 1, open-label, dose-ascending study to evaluate the safety and tolerability of the therapeutic radiopharmaceutical (131)I-MIP-1095 for the treatment of metastatic castration-resistant prostate cancer Journal Article

  

Authors:	Laccetti, A. L.; Bodei, L.; O'Donoghue, J. A.; Weber, W. A.; Morris, M. J.
Article Title:	A phase 1, open-label, dose-ascending study to evaluate the safety and tolerability of the therapeutic radiopharmaceutical (131)I-MIP-1095 for the treatment of metastatic castration-resistant prostate cancer
Abstract:	PURPOSE 131I-MIP-1095 is a targeted radiotherapeutic that contains 131I, a β-particle emitter, and MIP-1095, a urea-based ligand for prostate-specific membrane antigen. We report the first phase 1, dose-escalation study of 131I-MIP-1095 in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods This study enrolled men with mCRPC refractory to second-generation antiandrogen(s) and taxane chemotherapy. Dosimetry/biodistribution assessments were performed. Safety and tolerability were determined in subjects who qualified for therapeutic administration of 131I-MIP-1095 with maximum tolerated activity examined in a dose-ascending manner (3 + 3 design methodology). Disease outcomes including prostate-specific antigen (PSA) change, tumor response, survival, and circulating tumor cell concentration were assessed. Results A total of 9 subjects with mCRPC were included in this study. On the basis of dosimetry results, 5 of 9 patients were treated: 3 in cohort 1 (50 mCi) and 2 in cohort 2 (75 mCi). Accrual stopped at the cohort 2 activity level in response to the US Food and Drug Administration mandate for 131I-MIP-1095 manufacturing concerns. Parotid/salivary glands (3.5 Gy/Bq), liver (2.2 Gy/Bq), kidneys (1.3 Gy/Bq), and spleen (0.7 Gy/Bq) demonstrated the greatest extent of 131I-MIP-1095 exposure. There were no deaths, serious adverse events, or drug discontinuations due to treatment-emergent adverse events. Grade 1-2 thrombocytopenia, anemia, leukopenia, and dry mouth most commonly occurred. One subject (33.3%) exhibited maximum decline for the PSA response of 50% or greater. Conclusion 131I-MIP-1095 demonstrated favorable dosimetry, biodistribution, and safety, as well as a modest PSA response supporting further investigation for treatment of men with mCRPC. © Wolters Kluwer Health, Inc. All rights reserved.
Keywords:	treatment outcome; clinical trial; antineoplastic agents; antineoplastic agent; radiopharmaceuticals; prostate specific antigen; prostate cancer; prostate-specific antigen; radioactive iodine; tissue distribution; iodine radioisotopes; radiopharmaceutical agent; phase 1 clinical trial; castration resistant prostate cancer; psma; iodine-131; humans; human; male; prostatic neoplasms, castration-resistant; radiotherapeutic; <sup>131</sup>i-mip-1095; 2-(3-(1-carboxy-5-(3-(4-iodobphenyl)ureido)pentyl)ureido)pentanedioic acid
Journal Title:	Clinical Nuclear Medicine
Volume:	48
Issue:	11
ISSN:	0363-9762
Publisher:	Lippincott Williams & Wilkins
Date Published:	2023-11-01
Start Page:	937
End Page:	944
Language:	English
DOI:	10.1097/rlu.0000000000004818
PUBMED:	37812518
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85173300353&doi=10.1097%2fRLU.0000000000004818&partnerID=40&md5=46256bb2b7703ac2da6d9c5f1f6545ed
Notes:	Article -- Source: Scopus

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