Phase 1b study of tirabrutinib in combination with idelalisib or entospletinib in previously treated B-cell lymphoma

Franck Morschhauser; Martin J.S. Dyer; Harriet S. Walter; Alexey V. Danilov; Loic Ysebaert; Daniel James Hodson; Christopher Fegan; Simon A. Rule; John Radford; Guillaume Cartron; Krimo Bouabdallah; Andrew John Davies; Stephen Spurgeon; Nishanthan Rajakumaraswamy; Biao Li; Rita Humeniuk; Xi Huang; Pankaj Bhargava; Juliane M. Jürgensmeier; Gilles Salles

doi:10.1038/s41375-020-01108-x

Phase 1b study of tirabrutinib in combination with idelalisib or entospletinib in previously treated B-cell lymphoma

Franck Morschhauser^*, Martin J.S. Dyer, Harriet S. Walter, Alexey V. Danilov, Loic Ysebaert, Daniel James Hodson, Christopher Fegan, Simon A. Rule, John Radford, Guillaume Cartron, Krimo Bouabdallah, Andrew John Davies, Stephen Spurgeon, Nishanthan Rajakumaraswamy, Biao Li, Rita Humeniuk, Xi Huang, Pankaj Bhargava, Juliane M. Jürgensmeier, Gilles Salles

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Journal	Leukemia
DOIs	https://doi.org/10.1038/s41375-020-01108-x
Publication status	Published - 17 Dec 2020

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Manchester Cancer Research Centre

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Morschhauser, F., Dyer, M. J. S., Walter, H. S., Danilov, A. V., Ysebaert, L., Hodson, D. J., Fegan, C., Rule, S. A., Radford, J., Cartron, G., Bouabdallah, K., Davies, A. J., Spurgeon, S., Rajakumaraswamy, N., Li, B., Humeniuk, R., Huang, X., Bhargava, P., Jürgensmeier, J. M., & Salles, G. (2020). Phase 1b study of tirabrutinib in combination with idelalisib or entospletinib in previously treated B-cell lymphoma. Leukemia. https://doi.org/10.1038/s41375-020-01108-x

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title = "Phase 1b study of tirabrutinib in combination with idelalisib or entospletinib in previously treated B-cell lymphoma",

abstract = "B-cell receptor (BCR) signaling pathway inhibitors (including Bruton{\textquoteright}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.",

author = "Franck Morschhauser and Dyer, {Martin J.S.} and Walter, {Harriet S.} and Danilov, {Alexey V.} and Loic Ysebaert and Hodson, {Daniel James} and Christopher Fegan and Rule, {Simon A.} and John Radford and Guillaume Cartron and Krimo Bouabdallah and Davies, {Andrew John} and Stephen Spurgeon and Nishanthan Rajakumaraswamy and Biao Li and Rita Humeniuk and Xi Huang and Pankaj Bhargava and J{\"u}rgensmeier, {Juliane M.} and Gilles Salles",

year = "2020",

month = dec,

day = "17",

doi = "10.1038/s41375-020-01108-x",

language = "English",

journal = "Leukemia",

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publisher = "Springer Nature",

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Morschhauser, F, Dyer, MJS, Walter, HS, Danilov, AV, Ysebaert, L, Hodson, DJ, Fegan, C, Rule, SA, Radford, J, Cartron, G, Bouabdallah, K, Davies, AJ, Spurgeon, S, Rajakumaraswamy, N, Li, B, Humeniuk, R, Huang, X, Bhargava, P, Jürgensmeier, JM & Salles, G 2020, 'Phase 1b study of tirabrutinib in combination with idelalisib or entospletinib in previously treated B-cell lymphoma', Leukemia. https://doi.org/10.1038/s41375-020-01108-x

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T1 - Phase 1b study of tirabrutinib in combination with idelalisib or entospletinib in previously treated B-cell lymphoma

AU - Morschhauser, Franck

AU - Dyer, Martin J.S.

AU - Walter, Harriet S.

AU - Danilov, Alexey V.

AU - Ysebaert, Loic

AU - Hodson, Daniel James

AU - Fegan, Christopher

AU - Rule, Simon A.

AU - Radford, John

AU - Cartron, Guillaume

AU - Bouabdallah, Krimo

AU - Davies, Andrew John

AU - Spurgeon, Stephen

AU - Rajakumaraswamy, Nishanthan

AU - Li, Biao

AU - Humeniuk, Rita

AU - Huang, Xi

AU - Bhargava, Pankaj

AU - Jürgensmeier, Juliane M.

AU - Salles, Gilles

PY - 2020/12/17

Y1 - 2020/12/17

N2 - 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.

AB - 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.

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DO - 10.1038/s41375-020-01108-x

M3 - Article

AN - SCOPUS:85097673608

SN - 0887-6924

JO - Leukemia

JF - Leukemia

ER -

Phase 1b study of tirabrutinib in combination with idelalisib or entospletinib in previously treated B-cell lymphoma

Abstract

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