Phase II study of copanlisib, a PI3K ...
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Article dans une revue scientifique
DOI :
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Title :
Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma.
Author(s) :
Dreyling, Martin [Auteur]
Klinikum der Universität [München]
Morschhauser, Franck [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Bouabdallah, Kamal [Auteur]
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
Bron, D [Auteur]
Ecole de Santé Publique [Université Libre de Bruxelles]
Cunningham, David [Auteur]
IBM Thomas J. Watson Research Center
Assouline, Sarit [Auteur]
Jewish General Hospital
Verhoef, Gregor [Auteur]
University Hospitals Leuven [Leuven]
Linton, K [Auteur]
Manchester University NHS Foundation Trust [MFT]
Thieblemont, Catherine [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]
Vitolo, Umberto [Auteur]
Università degli studi di Torino = University of Turin [UNITO]
Hiemeyer, Florian [Auteur]
Bayer Pharma AG [Berlin]
Giurescu, Marius [Auteur]
Bayer Pharma AG [Berlin]
Garcia-Vargas, Jose [Auteur]
Bayer HealthCare Pharmaceuticals Inc [Whippany]
Gorbatchevsky, I [Auteur]
Bayer HealthCare Pharmaceuticals Inc [Whippany]
Liu, Li [Auteur]
Bayer HealthCare Pharmaceuticals Inc [Whippany]
Koechert, Karl [Auteur]
Bayer Pharma AG [Berlin]
Pena, Carol [Auteur]
Bayer HealthCare Pharmaceuticals Inc [Whippany]
Neves, M [Auteur]
Childs, BH [Auteur]
Bayer HealthCare Pharmaceuticals Inc [Whippany]
Zinzani Pier, Luigi [Auteur]
Klinikum der Universität [München]
Morschhauser, Franck [Auteur]

Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Bouabdallah, Kamal [Auteur]
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
Bron, D [Auteur]
Ecole de Santé Publique [Université Libre de Bruxelles]
Cunningham, David [Auteur]
IBM Thomas J. Watson Research Center
Assouline, Sarit [Auteur]
Jewish General Hospital
Verhoef, Gregor [Auteur]
University Hospitals Leuven [Leuven]
Linton, K [Auteur]
Manchester University NHS Foundation Trust [MFT]
Thieblemont, Catherine [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]
Vitolo, Umberto [Auteur]
Università degli studi di Torino = University of Turin [UNITO]
Hiemeyer, Florian [Auteur]
Bayer Pharma AG [Berlin]
Giurescu, Marius [Auteur]
Bayer Pharma AG [Berlin]
Garcia-Vargas, Jose [Auteur]
Bayer HealthCare Pharmaceuticals Inc [Whippany]
Gorbatchevsky, I [Auteur]
Bayer HealthCare Pharmaceuticals Inc [Whippany]
Liu, Li [Auteur]
Bayer HealthCare Pharmaceuticals Inc [Whippany]
Koechert, Karl [Auteur]
Bayer Pharma AG [Berlin]
Pena, Carol [Auteur]
Bayer HealthCare Pharmaceuticals Inc [Whippany]
Neves, M [Auteur]
Childs, BH [Auteur]
Bayer HealthCare Pharmaceuticals Inc [Whippany]
Zinzani Pier, Luigi [Auteur]
Journal title :
Annals of oncology
Abbreviated title :
Ann. Oncol.
Volume number :
28
Pages :
2169-2178
Publication date :
2017-09
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Background: Copanlisib is a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α- and δ-isoforms. Patients and methods: This phase II study evaluated the response rate of copanlisib ...
Show more >Background: Copanlisib is a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α- and δ-isoforms. Patients and methods: This phase II study evaluated the response rate of copanlisib administered intravenously on days 1, 8, and 15 of a 28-day cycle, in patients with indolent or aggressive malignant lymphoma. Archival tumor tissues were used for immunohistochemistry, gene-expression profiling, and mutation analysis. Results: Thirty-three patients with indolent lymphoma and 51 with aggressive lymphoma received copanlisib. Follicular lymphoma (48.5%) and peripheral T-cell lymphoma (33.3%) were the most common histologic subtypes. Most patients (78.6%) had received prior rituximab and 54.8% were rituximab-refractory. Median duration of treatment was 23 and 8 weeks in the indolent and aggressive cohorts, respectively (overall range 2-138). Eighty patients were evaluated for efficacy. The objective response rate was 43.7% (14/32) in the indolent cohort and 27.1% (13/48) in the aggressive cohort; median progression-free survival was 294 days (range 0-874) and 70 days (range 0-897), respectively; median duration of response was 390 days (range 0-825) and 166 days (range 0-786), respectively. Common adverse events included hyperglycemia (57.1%; grade ≥3, 23.8%), hypertension (54.8%; grade ≥3, 40.5%), and diarrhea (40.5%; grade ≥3, 4.8%), all generally manageable. Neutropenia occurred in 28.6% of patients (grade 4, 11.9%). Molecular analyses showed enhanced antitumor activity in tumors with upregulated phosphatidylinositol 3-kinase pathway gene expression. Conclusion: Intravenous copanlisib demonstrated promising efficacy and manageable toxicity in heavily pretreated patients with various subtypes of indolent and aggressive malignant lymphoma. Subtype-specific studies of copanlisib in patients with follicular, peripheral T-cell, and mantle cell lymphomas are ongoing. This trial is registered with ClinicalTrials.gov number NCT01660451 (Part A).Show less >
Show more >Background: Copanlisib is a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α- and δ-isoforms. Patients and methods: This phase II study evaluated the response rate of copanlisib administered intravenously on days 1, 8, and 15 of a 28-day cycle, in patients with indolent or aggressive malignant lymphoma. Archival tumor tissues were used for immunohistochemistry, gene-expression profiling, and mutation analysis. Results: Thirty-three patients with indolent lymphoma and 51 with aggressive lymphoma received copanlisib. Follicular lymphoma (48.5%) and peripheral T-cell lymphoma (33.3%) were the most common histologic subtypes. Most patients (78.6%) had received prior rituximab and 54.8% were rituximab-refractory. Median duration of treatment was 23 and 8 weeks in the indolent and aggressive cohorts, respectively (overall range 2-138). Eighty patients were evaluated for efficacy. The objective response rate was 43.7% (14/32) in the indolent cohort and 27.1% (13/48) in the aggressive cohort; median progression-free survival was 294 days (range 0-874) and 70 days (range 0-897), respectively; median duration of response was 390 days (range 0-825) and 166 days (range 0-786), respectively. Common adverse events included hyperglycemia (57.1%; grade ≥3, 23.8%), hypertension (54.8%; grade ≥3, 40.5%), and diarrhea (40.5%; grade ≥3, 4.8%), all generally manageable. Neutropenia occurred in 28.6% of patients (grade 4, 11.9%). Molecular analyses showed enhanced antitumor activity in tumors with upregulated phosphatidylinositol 3-kinase pathway gene expression. Conclusion: Intravenous copanlisib demonstrated promising efficacy and manageable toxicity in heavily pretreated patients with various subtypes of indolent and aggressive malignant lymphoma. Subtype-specific studies of copanlisib in patients with follicular, peripheral T-cell, and mantle cell lymphomas are ongoing. This trial is registered with ClinicalTrials.gov number NCT01660451 (Part A).Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
CHU Lille
CHU Lille
Collections :
Research team(s) :
Innovation/évaluation des médicaments injectables
Submission date :
2019-02-26T17:07:09Z
2021-06-07T08:10:54Z
2021-06-07T08:10:54Z
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