Titre :

A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies

Auteur(s) :

Walter Harriet, S [Auteur]
Rule, Simon [Auteur]
Dyer Martin J, S [Auteur]
Karlin, Lionel [Auteur]
Jones, Ceri [Auteur]
Cazin, Bruno [Auteur]
Quittet, Philippe [Auteur]
Shah, Nimish [Auteur]
Hutchinson Claire, V [Auteur]
Honda, Hideyuki [Auteur]
Duffy, Kevin [Auteur]
Birkett, Joseph [Auteur]
Jamieson, Virginia [Auteur]
Courtenay-Luck, Nigel [Auteur]
Yoshizawa, Toshio [Auteur]
Sharpe, John [Auteur]
Ohno, Tomoya [Auteur]
Abe, Shinichiro [Auteur]
Nishimura, Akihisa [Auteur]
Cartron, Guillaume [Auteur]
Morschhauser, Franck [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Fegan, Christopher [Auteur]
Salles, Gilles [Auteur]

Titre de la revue :

Blood

Nom court de la revue :

Blood

Numéro :

127

Pagination :

411-419

Date de publication :

2016

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

We report the results of a multicenter phase 1 dose-escalation study of the selective Bruton tyrosine kinase (BTK) inhibitor ONO/GS-4059 in 90 patients with relapsed/refractory B-cell malignancies. There were 9 dose-escalation ...
Lire la suite >We report the results of a multicenter phase 1 dose-escalation study of the selective Bruton tyrosine kinase (BTK) inhibitor ONO/GS-4059 in 90 patients with relapsed/refractory B-cell malignancies. There were 9 dose-escalation cohorts ranging from 20 mg to 600 mg once daily with twice-daily regimens of 240 mg and 300 mg. Twenty-four of 25 evaluable chronic lymphocytic leukemia (CLL) patients (96%) responded to ONO/GS-4059, with a median treatment duration of 80 weeks; 21 CLL patients remain on treatment. Lymph node responses were rapid and associated with a concurrent lymphocytosis. Eleven of 12 evaluable patients with mantle cell lymphoma (92%) responded (median treatment duration, 40 weeks). Eleven of 31 non-germinal center B-cell diffuse large B-cell lymphoma patients (35%) responded but median treatment duration was 12 weeks due to development of progressive disease. ONO/GS-4059 was very well tolerated with 75% of adverse events (AEs) being Common Toxicity Criteria for Adverse Events version 4.0 grade 1 or grade 2. Grade 3/4 AEs were mainly hematologic and recovered spontaneously during therapy. One CLL patient experienced a grade 3 treatment-related bleeding event (spontaneous muscle hematoma) but no clinically significant diarrhea, cardiac dysrhythmias, or arthralgia were observed. No maximal tolerated dose (MTD) was reached in the CLL cohort. In the non-Hodgkin lymphoma cohort, 4 patients developed a dose-limiting toxicity, yielding an MTD of 480 mg once daily. ONO/GS-4059 has significant activity in relapsed/refractory B-cell malignancies without major drug-related toxicity. The selectivity of ONO/GS-4059 should confer advantages in combination therapies. This trial was registered at www.clinicaltrials.gov as #NCT01659255.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CHU Lille

Collections :

• Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365

Équipe(s) de recherche :

Innovation/évaluation des médicaments injectables

Date de dépôt :

2019-02-26T17:07:31Z