1. Phase 1b study of tirabrutinib in combination with idelalisib or entospletinib in previously treated B-cell lymphoma
- Author
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Nishanthan Rajakumaraswamy, Simon Rule, Krimo Bouabdallah, John Radford, Loic Ysebaert, Christopher Fegan, Stephen E. Spurgeon, Gilles Salles, Alexey V. Danilov, Rita Humeniuk, Xi Huang, Pankaj Bhargava, Guillaume Cartron, Biao Li, Martin J. S. Dyer, Harriet S. Walter, Andrew Davies, Daniel J. Hodson, Franck Morschhauser, Juliane M. Jürgensmeier, Morschhauser, Franck [0000-0002-3714-9824], Walter, Harriet S [0000-0003-2618-711X], Hodson, Daniel James [0000-0001-6225-2033], Rule, Simon A [0000-0001-8937-6351], Rajakumaraswamy, Nishanthan [0000-0002-0226-0637], Salles, Gilles [0000-0002-9541-8666], Apollo - University of Cambridge Repository, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Ernest and Helen Scott Haematological Research Institute, University of Leicester, City of Hope National Medical Center, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Cambridge [UK] (CAM), University Hospital of Wales (UHW), Plymouth University, University of Manchester [Manchester], The Christie NHS Foundation Trust [Manchester, Royaume-Uni], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], University of Southampton, Knight Cancer Institute, Oregon Health and Science University [Portland] (OHSU), Gilead Sciences, Inc. [Foster City, CA, USA], Hospices Civils de Lyon (HCL), Université de Lyon, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Herrada, Anthony, CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospital of Wales [Cardiff, UK], Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Walter, Harriet S. [0000-0003-2618-711X], and Rule, Simon A. [0000-0001-8937-6351]
- Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,Adult ,Male ,Cancer Research ,Letter ,Entospletinib ,Indazoles ,Lymphoma, B-Cell ,Cancer therapy ,Drug development ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Antineoplastic Agents ,03 medical and health sciences ,0302 clinical medicine ,692/699/67/1059 ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,immune system diseases ,Phase (matter) ,hemic and lymphatic diseases ,medicine ,Humans ,692/308/153 ,B-cell lymphoma ,Purine metabolism ,Protein Kinase Inhibitors ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Aged ,Quinazolinones ,0303 health sciences ,Manchester Cancer Research Centre ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,Imidazoles ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Hematology ,Middle Aged ,medicine.disease ,3. Good health ,Pyrimidines ,Oncology ,Purines ,030220 oncology & carcinogenesis ,Pyrazines ,Cancer research ,Female ,Idelalisib ,Previously treated ,business - Abstract
B-cell receptor (BCR) signaling pathway inhibitors (including Bruton’s tyrosine kinase [BTK] inhibitors, and phosphatidylinositol-3 kinase inhibitors [PI3Ki]) have shown clinical efficacy in non-Hodgkin lymphoma (NHL). However, responses to these agents have been limited in depth and duration. This may be due to resistance to PI3Kδ and BTK inhibitors as monotherapy [1,2,3,4,5]. The emergence of resistant clones may be addressed by combining these 2 classes of drugs. Furthermore, tolerability of these drug classes has been a concern. Combination therapy using lower doses of one or more classes of inhibitors may address some limitations.
- Published
- 2021
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