Strategies for clinical development of monoclonal antibodies beyond first-in-human trials: tested doses and rationale for dose selection.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY-NC-SA 4.0
ID Serval
serval:BIB_B98F6A7521FE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Strategies for clinical development of monoclonal antibodies beyond first-in-human trials: tested doses and rationale for dose selection.
Périodique
British journal of cancer
Auteur(s)
Viala M., Vinches M., Alexandre M., Mollevi C., Durigova A., Hayaoui N., Homicsko K., Cuenant A., Gongora C., Gianni L., Tosi D.
ISSN
1532-1827 (Electronic)
ISSN-L
0007-0920
Statut éditorial
Publié
Date de publication
06/03/2018
Peer-reviewed
Oui
Volume
118
Numéro
5
Pages
679-697
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Our previous survey on first-in-human trials (FIHT) of monoclonal antibodies (mAbs) showed that, due to their limited toxicity, the recommended phase II dose (RP2D) was only tentatively defined.
We identified, by MEDLINE search, articles on single-agent trials of mAbs with an FIHT included in our previous survey. For each mAb, we examined tested dose(s) and dose selection rationale in non-FIHTs (NFIHTs). We also assessed the correlation between doses tested in the registration trials (RTs) of all FDA-approved mAbs and the corresponding FIHT results.
In the 37 dose-escalation NFIHTs, the RP2D indication was still poorly defined. In phase II-III NFIHTs (n=103 on 37 mAbs), the FIHT RP2D was the only dose tested for five mAbs. For 16 mAbs, only doses different from the FIHT RP2D or the maximum administered dose (MAD) were tested and the dose selection rationale infrequently indicated. In the 60 RTs on 27 FDA-approved mAbs with available FIHT, the FIHT RP2D was tested only for two mAbs, and RT doses were much lower than the FIHT MAD.
The rationale beyond dose selection in phase II and III trials of mAbs is often unclear in published articles and not based on FIHT data.
Mots-clé
Antibodies, Monoclonal/administration & dosage, Antibodies, Monoclonal/therapeutic use, Antineoplastic Agents/administration & dosage, Antineoplastic Agents/therapeutic use, Clinical Decision-Making, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Dose-Response Relationship, Drug, Humans, Neoplasms/drug therapy, Research Design
Pubmed
Web of science
Création de la notice
15/02/2018 19:13
Dernière modification de la notice
20/08/2019 15:27
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