Clinical Development Strategies and Outcomes in First-in-Human Trials of Monoclonal Antibodies.

Details

Serval ID
serval:BIB_7060EBC53995
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Clinical Development Strategies and Outcomes in First-in-Human Trials of Monoclonal Antibodies.
Journal
Journal of Clinical Oncology
Author(s)
Tosi D., Laghzali Y., Vinches M., Alexandre M., Homicsko K., Fasolo A., Del Conte G., Durigova A., Hayaoui N., Gourgou S., Gianni L., Mollevi C.
ISSN
1527-7755 (Electronic)
ISSN-L
0732-183X
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
33
Number
19
Pages
2158-2165
Language
english
Abstract
PURPOSE: We conducted a comprehensive review of the design, implementation, and outcome of first-in-human (FIH) trials of monoclonal antibodies (mAbs) to clearly determine early clinical development strategies for this class of compounds.
METHODS: We performed a PubMed search using appropriate terms to identify reports of FIH trials of mAbs published in peer-reviewed journals between January 2000 and April 2013.
RESULTS: A total of 82 publications describing FIH trials were selected for analysis. Only 27 articles (33%) reported the criteria used for selecting the starting dose (SD). Dose escalation was performed using rule-based methods in 66 trials (80%). The median number of planned dose levels was five (range, two to 13). The median of the ratio between the highest planned dose and the SD was 27 (range, two to 3,333). Although in 56 studies (68%) at least one grade 3 or 4 toxicity event was reported, no dose-limiting toxicity was observed in 47 trials (57%). The highest planned dose was reached in all trials, but the maximum-tolerated dose (MTD) was defined in only 13 studies (16%). The median of the ratio between MTD and SD was eight (range, four to 1,000). The recommended phase II dose was indicated in 34 studies (41%), but in 25 (73%) of these trials, this dose was chosen without considering toxicity as the main selection criterion.
CONCLUSION: This literature review highlights the broad design heterogeneity of FIH trials testing mAbs. Because of the limited observed toxicity, the MTD was infrequently reached, and therefore, the recommended phase II dose for subsequent clinical trials was only tentatively defined.
Keywords
Antibodies, Monoclonal/adverse effects, Antibodies, Monoclonal/therapeutic use, Antineoplastic Agents/adverse effects, Antineoplastic Agents/therapeutic use, Clinical Trials as Topic, Dose-Response Relationship, Drug, Humans, Maximum Tolerated Dose, Neoplasms/drug therapy, Research Design
Pubmed
Web of science
Create date
19/10/2015 13:58
Last modification date
20/08/2019 15:29
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