Copanlisib in the treatment of non-Hodgkin lymphoma

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

• 1. Nogai H, Dörken B, Lenz G. Pathogenesis of non-Hodgkin’s lymphoma. J. Clin. Oncol. 29(14), 1803–1811 (2011).
  Medline CASGoogle Scholar
• 2. Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS. Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. Blood 107(1), 265–276 (2006).
  Medline CASGoogle Scholar
• 3. Niemann CU, Wiestner A. B-cell receptor signaling as a driver of lymphoma development and evolution. Semin Cancer Biol. 23(6), 410 421 (2013).
  Medline CASGoogle Scholar
• 4. Tzenaki N, Papakonstanti EA. p110δ PI3 kinase pathway: emerging roles in cancer. Front. Oncol. 3, 40 (2013). • Describes the PI3K pathway.
  MedlineGoogle Scholar
• 5. Okkenhaug K. Signaling by the phosphoinositide 3-kinase family in immune cells. Annu. Rev. Immunol. 31, 675–704 (2013).
  Medline CASGoogle Scholar
• 6. Pongas G, Cheson BD. PI3K signaling pathway in normal B cells and indolent B-cell malignancies. Semin. Oncol. 43(6), 647–654 (2016).
  Medline CASGoogle Scholar
• 7. Hu P, Mondino A, Skolnik E, Schlessinger J. Cloning of a novel, ubiquitously expressed human phosphatidylinositol 3-kinase and identification of its binding site on p85. Mol. Cell. Biol. 13(12), 7677–7688 (1993).
  Medline CASGoogle Scholar
• 8. Bi L, Okabe I, Bernard DJ, Wynshaw-Boris A, Nussbaum RL. Proliferative defect and embryonic lethality in mice homozygous for a deletion in the p110α subunit of phosphoinositide 3-kinase. J. Biol. Chem. 274(16), 10963–10968 (1999).
  Medline CASGoogle Scholar
• 9. Geering B, Cutillas PR, Nock G, Gharbi SI, Vanhaesebroeck B. Class IA phosphoinositide 3-kinases are obligate p85-p110 heterodimers. Proc. Natl Acad. Sci. USA 104(19), 7809–7814 (2007).
  Medline CASGoogle Scholar
• 10. Chantry D, Vojtek A, Kashishian A et al. p110δ, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed predominantly in leukocytes. J. Biol. Chem. 272(31), 19236–19241 (1997).
  Medline CASGoogle Scholar
• 11. Lim S, Haike K, De Vera L et al. Expression of PI3K isoforms and PTEN in follicular lymphoma and diffuse large B-cell lymphoma: 267. Hematol. Oncol. 33 (2015).
  Google Scholar
• 12. Liu N, Rowley BR, Bull CO et al. BAY 80–6946 is a highly selective intravenous PI3K inhibitor with potent p110α and p110δ activities in tumor cell lines and xenograft models. Mol. Cancer Ther. 12(11), 2319–2330 (2013).
  Medline CASGoogle Scholar
• 13. Seiler T, Hutter G, Dreyling M. The emerging role of PI3K inhibitors in the treatment of hematological malignancies: preclinical data and clinical progress to date. Drugs 76(6), 639–646 (2016).
  MedlineGoogle Scholar
• 14. Göckeritz E, Kerwien S, Baumann M et al. Efficacy of phosphatidylinositol‐3 kinase inhibitors with diverse isoform selectivity profiles for inhibiting the survival of chronic lymphocytic leukemia cells. Int. J. Cancer 137(9), 2234–2242 (2015).
  MedlineGoogle Scholar
• 15. Kater AP, Tonino SH, Spiering M et al. Final results of a Phase Ib study of the safety and efficacy of the PI3Kδ inhibitor acalisib (GS-9820) in relapsed/refractory lymphoid malignancies. Blood Cancer J. 8(2), 1–4 (2018).
  MedlineGoogle Scholar
• 16. Burris Iii HA, Flinn IW, Patel MR et al. Umbralisib, a novel PI3Kδ and casein kinase-1ε inhibitor, in relapsed or refractory chronic lymphocytic leukaemia and lymphoma: an open-label, Phase 1, dose-escalation, first-in-human study. Lancet Oncol. 19(4), 486–496 (2018).
  Medline CASGoogle Scholar
• 17. Shin N, Koblish H, Covington M et al. Abstract 2671: INCB050465, a novel PI3Kδ inhibitor, synergizes with PIM protein kinase inhibition to cause tumor regression in a model of DLBCL. Cancer Res. 75(Suppl. 15), 2671 (2015).
  Google Scholar
• 18. Cushing TD, Hao X, Shin Y et al. Discovery and in vivo evaluation of (S)-N-(1-(7-Fluoro-2-(pyridin-2-yl) quinolin-3-yl) ethyl)-9 H-purin-6-amine (AMG319) and related PI3Kδ inhibitors for inflammation and autoimmune disease. J. Med. Chem. 58(1), 480–511 (2015).
  Medline CASGoogle Scholar
• 19. O'Farrell M, Ventura R, Tai A et al. Preclinical characterization of PWT143, a novel selective and potent phosphatidylinositol 3-kinase delta (PI3K delta) inhibitor with ex-vivo activity in hematologic malignancies. CAL 20(40), 60–80 (2012).
  Google Scholar
• 20. Carlo-Stella C, Delarue R, Scarfo L et al. A First-in-human study of tenalisib (RP6530), a dual PI3K δ/γ inhibitor, in patients with relapsed/refractory hematologic malignancies: results from the European study. Clin. Lymphoma Myeloma Leuk. 20(2), 78–86 (2020).
  MedlineGoogle Scholar
• 21. Flinn IW, O'Brien S, Kahl B et al. Duvelisib, a novel oral dual inhibitor of PI3K-δ, γ, is clinically active in advanced hematologic malignancies. Blood 131(8), 877–887 (2018).
  Medline CASGoogle Scholar
• 22. Folkes AJ, Ahmadi K, Alderton WK et al. The identification of 2-(1 H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno [3, 2-d] pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J. Med. Chem. 51(18), 5522–5532 (2008).
  Medline CASGoogle Scholar
• 23. Burger MT, Pecchi S, Wagman A et al. Identification of NVP-BKM120 as a potent, selective, orally bioavailable class I PI3 kinase inhibitor for treating cancer. ACS Med. Chem. Lett. 2(10), 774–779 (2011).
  Medline CASGoogle Scholar
• 24. Patnaik A, Appleman L, Tolcher A 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. 27(10), 1928–1940 (2016). •• First-in-human study of copanlisib.
  Medline CASGoogle Scholar
• 25. Dreyling M, Santoro A, Mollica L et al. Phosphatidylinositol 3-kinase inhibition by copanlisib in relapsed or refractory indolent lymphoma. J. Clin. Oncol. 35(35), 3898–3905 (2017). •• Phase II study of copanlisib leading to US FDA approval in follicular lymphoma.
  Medline CASGoogle Scholar
• 26. Dreyling M, Santoro A, Mollica L et al. Long‐term safety and efficacy of the PI3K‐inhibitor copanlisib in patients with relapsed or refractory indolent lymphoma: 2‐year follow‐up of the CHRONOS‐1 study. Am. J. Hematol. 95, 362–371 (2019). •• Demonstrates long-term efficacy and safety data for copanlisib.
  Google Scholar
• 27. 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. 28(9), 2169–2178 (2017).
  Medline CASGoogle Scholar
• 28. Lenz G, Hawkes E, Verhoef G et al. Single-agent activity of phosphatidylinositol 3-kinase inhibition with copanlisib in patients with molecularly defined relapsed or refractory diffuse large B-cell lymphoma. Leukemia 1–14 (2020).
  MedlineGoogle Scholar
• 29. André F, Ciruelos E, Rubovszky G et al. Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N. Engl. J. Med. 380(20), 1929–1940 (2019).
  Medline CASGoogle Scholar
• 30. Morschhauser F, Machiels J-P, Salles G et al. On-target pharmacodynamic activity of the PI3K inhibitor copanlisib in paired biopsies from patients with malignant lymphoma and advanced solid tumors. Mol. Cancer Ther. 19(2), 468–478 (2020).
  Medline CASGoogle Scholar
• 31. Cheson BD, O'Brien S, Ewer MS et al. Optimal management of adverse events from copanlisib in the treatment of patients with non-Hodgkin lymphomas. Clin. Lymphoma Myeloma Leuk. 19(3), 135–141 (2019). •• Guidelines for managing copanlisib adverse events.
  MedlineGoogle Scholar
• 32. Gopal AK, Kahl BS, De Vos S et al. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma. N. Engl. J. Med. 370(11), 1008–1018 (2014).
  Medline CASGoogle Scholar
• 33. Furman RR, Sharman JP, Coutre SE et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N. Engl. J. Med. 370(11), 997–1007 (2014).
  Medline CASGoogle Scholar
• 34. Copiktra®(duvelisib), package insert. Verastem Oncology. Needham, MA, USA.
  Google Scholar
• 35. Fowler NH, Samaniego F, Jurczak W et al. Umbralisib monotherapy demonstrates efficacy and safety in patients with relapsed/refractory marginal zone lymphoma: a multicenter, open label, registration directed Phase II study. J. Clin. Oncol. 37(Suppl. 15), 7506–7506 (2019).
  Google Scholar
• 36. Zelenetz AD, Jagadeesh D, Reddy NM et al. Results of the PI3Kδ inhibitor ME-401 alone or with rituximab in relapsed/refractory (R/R) follicular lymphoma (FL). J. Clin. Oncol. 37(Suppl. 15), 7512–7512 (2019).
  Google Scholar
• 37. Gaudio E, Kwee I, Spriano F et al. Abstract 154: the phosphatidylinositol-3-kinase (PI3K) inhibitor (i) copanlisib is active in preclinical models of B-cell lymphomas as single agent and in combination with conventional and targeted agents including venetoclax and palbociclib. Cancer Res. 77(Suppl. 13), 154 (2017).
  Google Scholar
• 38. Casulo C, Byrtek M, Dawson KL et al. Early relapse of follicular lymphoma after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for death: an analysis from the National LymphoCare Study. J. Clin. Oncol. 33(23), 2516 (2015).
  Medline CASGoogle Scholar
• 39. Dreyling M, Santoro A, Leppä S et al. Efficacy and safety in high-risk relapsed or refractory indolent follicular lymphoma patients treated with copanlisib. Hematol. Oncol. 37(Suppl. 2), 387–389 (2019).
  Google Scholar
• 40. Gopal AK, Kahl BS, Flowers CR et al. Idelalisib is effective in patients with high-risk follicular lymphoma and early relapse after initial chemoimmunotherapy. Blood 129(22), 3037–3039 (2017).
  Medline CASGoogle Scholar