Copanlisib: First Global Approval


Bayer are developing copanlisib (Aliqopa™)—a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor—as a treatment for various haematological and solid malignancies. The US FDA has granted copanlisib accelerated approval for the treatment of adults with relapsed follicular lymphoma who have received at least two prior systemic therapies based on the results of a phase II trial. Phase III trials are underway evaluating copanlisib as treatment for relapsed/refractory diffuse large B-cell lymphoma and in combination with rituximab or rituximab-based chemotherapy or standard immunochemotherapy in patients with relapsed indolent B-cell non-Hodgkin’s lymphoma. Phase I/II studies are underway in relapsed or refractory peripheral T-cell or NK/T-cell lymphoma, advanced cholangiocarcinoma, hormone receptor-positive HER2-negative stage I-IV breast cancer, HER2-positive breast cancer and recurrent and/or metastatic head and neck squamous cell carcinomas harbouring a PI3KCA mutation/amplification and/or a PTEN loss. This article summarizes the milestones in the development of copanlisib leading to this first approval for relapsed follicular lymphoma.

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  1. 1.

    Liu N, Rowley BR, Bull CO, et al. BAY 80-6946 is a highly selective intravenous pI3K inhibitor with potent p110alpha and p110delta activities in tumor cell lines and xenograft models. Mol Cancer Ther. 2013;12(11):2319–30.

    Article  PubMed  CAS  Google Scholar 

  2. 2.

    Bayer. FDA grants Bayer priority review for investigational compound copanlisib in follicular lymphoma [media release]. 17 May 2017.

  3. 3.

    FDA. Aliqopa (Copanlisib) prescribing information. 2017. Accessed 10 Oct 2017.

  4. 4.

    Glauer J, Pletz N, Schon M, et al. A novel selective small-molecule PI3K inhibitor is effective against human multiple myeloma in vitro and in vivo. Blood Cancer J. 2013;3:e141.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. 5.

    Paul J, Wengner AM, Petrova E, et al. Copanlisib attenuates both BCR-dependent and BCR-independent activation of NFKB in DLBCL cells [abstract no. 268]. Hematol Oncol. 2015;33(Suppl 1):235.

    Google Scholar 

  6. 6.

    Zoellner A, Arnd J, Hutter G, et al. Efficacy of the pan PI3K-inhibitor copanlisib compared to selective PI3K-a,-b,-delta inhibitors in mantle cell lymphoma (MCL) [abstract no. E1375]. Haematologica. 2015;100(Suppl 1):551.

    Google Scholar 

  7. 7.

    Patnaik A, Appleman LJ, Tolcher AW, et al. First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin’s lymphomas. Ann Oncol. 2016;27:1928–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. 8.

    Gerisch M, Schwarz T, Lang D, et al. Pharmacokinetics of intravenous pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor [14C]copanlisib (BAY 80-6946) in a mass balance study in healthy male volunteers. Cancer Chemother Pharmacol. 2017;80(3):535–44.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. 9.

    Reif S, Ahsman M, Jentsch G, et al. Use of a population pharmacokinetic approach and time-to-event analysis to support the clinical recommendation of a flat dosing of copanlisib in cancer patients [abstract no. PI-093]. Clin Pharmacol Ther. 2016;99(Suppl 1):S55.

    Google Scholar 

  10. 10.

    Gerecitano J, Santoro A, Leppa S, et al. Safety run-in of copanlisib in combination with rituximab plus bendamustine in patients with relapsed indolent non-Hodgkin’s lymphoma [abstract no. 477]. Hematol Oncol. 2017;35(Suppl 2):408–10.

    Article  Google Scholar 

  11. 11.

    Dreyling M, Morschhauser F, Bouabdallah K, et al. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann Oncol. 2017;28(9):2169–78.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. 12.

    Dreyling M, Santoro A, Mollica L, et al. Phosphatidylinositol 3-kinase inhibition by copanlisib in relapsed or refractory indolent lymphoma. J Clin Oncol. 2017.

    Article  PubMed  Google Scholar 

  13. 13.

    Lenz G, Hawkes E, Verhoef G, et al. Clinical outcomes and molecular characterization from a phase II study of copanlisib in patients with relapsed or refractory diffuse large B-cell lymphoma [abstract no. 57]. Hematol Oncol. 2017;35(Suppl 2):68–9.

    Article  Google Scholar 

  14. 14.

    Ramanathan RK, Von Hoff DD, Eskens F, et al. A phase 1b trial of PI3K inhibitor copanlisib (BAY 80-6946) combined with the allosteric-MEK inhibitor refametinib (BAY 86-9766) in patients with advanced cancer [abstract no. 2588]. J Clin Oncol Conf. 2014;32(Suppl 1).

  15. 15.

    Kim RD, Alberts SR, Renshaw FG, et al. Phase 1 dose escalation study of copanlisib (BAY 80-6946) in combination with gemcitabine or gemcitabine-cisplatin in advanced cancer patients [abstract no. 2610]. J Clin Oncol Conf. 2014;32(Suppl 1).

  16. 16.

    Doi T, Fuse N, Yoshino T, et al. A phase I study of intravenous PI3K inhibitor copanlisib in Japanese patients with advanced or refractory solid tumors. Cancer Chemother Pharmacol. 2017;79:89–98.

    Article  PubMed  CAS  Google Scholar 

  17. 17.

    Nowakowski GS, Gorbatchevsky I, Hiemeyer F, et al. A randomized, double-blind phase III study of phosphatidylinositol 3 kinase alpha/delta inhibitor copanlisib versus placebo in patients with rituximab refractory indolent non Hodgkin’s lymphoma (iNHL): CHRONOS2 [abstract no. CT084]. Cancer Res. 2016;76(14 Suppl).

  18. 18.

    Gerecitano JF, Zinzani PL, Zheng HX, et al. Phase III randomized, double-blind, controlled studies of the PI3K inhibitor copanlisib in combination with rituximab or rituximab-based chemotherapy in subjects with relapsed indolent B-cell non-Hodgkin’s lymphoma (iNHL): CHRONOS-3 and CHRONOS-4 [abstract no. CT085]. Cancer Res. 2016;76(14 Suppl).

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Correspondence to Anthony Markham.

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The preparation of this review was not supported by any external funding.

Conflict of interest

During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. A. Markham, a contracted employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

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Markham, A. Copanlisib: First Global Approval. Drugs 77, 2057–2062 (2017).

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