Duvelisib: a phosphoinositide-3 kinase δ/γ inhibitor for chronic lymphocytic leukemia

References

• Rozman C, Montserrat E. Chronic lymphocytic leukemia. N Engl J Med. 1995;333:1052–1057.
   PubMed Web of Science ®Google Scholar
• Marti GE, Zenger V, Caproaso NE, et al. Antigenic expression of B-cell chronic lymphocytic leukemic lymphocytes. Anal Quant Cytol Histol. 1989;11:315–323.
   PubMed Web of Science ®Google Scholar
• Matutes E, Owusu-Ankomah K, Morilla R, et al. The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia. 1994;8:1640–1645.
   PubMed Web of Science ®Google Scholar
• Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016;66:271–289.
   PubMed Web of Science ®Google Scholar
• Hernandez JA, Land KJ, McKenna RW. Leukemias, myeloma, and other lymphoreticular neoplasms. Cancer. 1995;75:381–394.
   PubMed Web of Science ®Google Scholar
• Kitada S, Andersen J, Akar S, et al. Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with in vitro and in vivo chemoresponses. Blood. 1998;91:3379–3389.
   PubMed Web of Science ®Google Scholar
• Orchard JA, Ibbotson RE, Davis Z, et al. ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet. 2004;363:105–111.
   PubMed Web of Science ®Google Scholar
• Rassenti LZ, Huynh L, Toy TL, et al. ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med. 2004;351:893–901.
   PubMed Web of Science ®Google Scholar
• Damle RN, Batliwalla FM, Ghiotto F, et al. Telomere length and telomerase activity delineate distinctive replicative features of the B-CLL subgroups defined by immunoglobulin V gene mutations. Blood. 2004;103:375–382.
   PubMed Web of Science ®Google Scholar
• Woyach JA, Johnson AJ, Byrd JC. The B-cell receptor signaling pathway as a therapeutic target in CLL. Blood. 2012;120:1175–1184.
   PubMed Web of Science ®Google Scholar
• Aiba Y, Kameyama M, Yamazaki T, et al. Regulation of B-cell development by BCAP and CD19 through their binding to phosphoinositide 3-kinase. Blood. 2008;111:1497–1503.
   PubMed Web of Science ®Google Scholar
• Deane JA, Fruman DA. Phosphoinositide 3-kinase: diverse roles in immune cell activation. Annu Rev Immunol. 2004;22:563–598.
   PubMed Web of Science ®Google Scholar
• Omori SA, Cato MH, Anzelon-Mills A, et al. Regulation of class-switch recombination and plasma cell differentiation by phosphatidylinositol 3-kinase signaling. Immunity. 2006;25:545–557.
   PubMed Web of Science ®Google Scholar
• Verkoczy L, Duong B, Skog P, et al. Basal B cell receptor-directed phosphatidylinositol 3-kinase signaling turns off RAGs and promotes B cell-positive selection. J Immunol. 2007;178:6332–6341.
   PubMed Web of Science ®Google Scholar
• Borlado LR, Redondo C, Alvarez B, et al. Increased phosphoinositide 3-kinase activity induces a lymphoproliferative disorder and contributes to tumor generation in vivo. FASEB J. 2000;14:895–903.
   PubMed Web of Science ®Google Scholar
• Fruman DA, Meyers RE, Cantley LC. Phosphoinositide kinases. Annu Rev Biochem. 1998;67:481–507.
   PubMed Web of Science ®Google Scholar
• Herman SE, Gordon AL, Wagner AJ, et al. Phosphatidylinositol 3-kinase-delta inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals. Blood. 2010;116:2078–2088.
   PubMed Web of Science ®Google Scholar
• Sujobert P, Bardet V, Cornillet-Lefebvre P, et al. Essential role for the p110delta isoform in phosphoinositide 3-kinase activation and cell proliferation in acute myeloid leukemia. Blood. 2005;106:1063–1066.
   PubMed Web of Science ®Google Scholar
• Miller BW, Przepiorka D, De Claro RA, et al. FDA approval: idelalisib monotherapy for the treatment of patients with follicular lymphoma and small lymphocytic lymphoma. Clin Cancer Res. 2015;21:1525–1529.
   PubMed Web of Science ®Google Scholar
• Yang Q, Modi P, Newcomb T, et al. Idelalisib: first-in-class PI3K delta inhibitor for the treatment of chronic lymphocytic leukemia, small lymphocytic leukemia, and follicular lymphoma. Clin Cancer Res. 2015;21:1537–1542.
   PubMed Web of Science ®Google Scholar
• Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Reviews Genet. 2006 Aug;7(8):606–619.
   PubMed Web of Science ®Google Scholar
• Liu P, Cheng H, Roberts TM, et al. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627–644.
   PubMed Web of Science ®Google Scholar
• Vanhaesebroeck B, Guillermet-Guibert J, Graupera M, et al. The emerging mechanisms of isoform-specific PI3K signalling. Nat Rev Mol Cell Biol. 2010 May;11(5):329–341.
   PubMed Web of Science ®Google Scholar
• Mellor P, Furber LA, Nyarko JN, et al. Multiple roles for the p85alpha isoform in the regulation and function of PI3K signalling and receptor trafficking. Biochem J. 2012 Jan 1;441(1):23–37.
   PubMed Web of Science ®Google Scholar
• Katso R, Okkenhaug K, Ahmadi K, et al. Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol. 2001;17:615–675.
   PubMed Web of Science ®Google Scholar
• Cantley LC. The phosphoinositide 3-kinase pathway. Science. 2002 May 31;296(5573):1655–1657.
   PubMed Web of Science ®Google Scholar
• Filippa N, Sable CL, Hemmings BA, et al. Effect of phosphoinositide-dependent kinase 1 on protein kinase B translocation and its subsequent activation. Mol Cell Biol. 2000 Aug;20(15):5712–5721.
   PubMed Web of Science ®Google Scholar
• Stokoe D, Stephens LR, Copeland T, et al. Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. Science. 1997 Jul 25;277(5325):567–570.
   PubMed Web of Science ®Google Scholar
• Miletic AV, Anzelon-Mills AN, Mills DM, et al. Coordinate suppression of B cell lymphoma by PTEN and SHIP phosphatases. J Exp Med. 2010 Oct 25;207(11):2407–2420.
   PubMed Web of Science ®Google Scholar
• Bellacosa A, Kumar CC, Di Cristofano A, et al. Activation of AKT kinases in cancer: implications for therapeutic targeting. Adv Cancer Res. 2005;94:29–86.
   PubMed Web of Science ®Google Scholar
• Okkenhaug K, Vanhaesebroeck B. PI3K in lymphocyte development, differentiation and activation. Nat Rev Immunol. 2003 Apr;3(4):317–330.
   PubMed Web of Science ®Google Scholar
• Hennessy BT, Smith DL, Ram PT, et al. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov. 2005 Dec;4(12):988–1004.
   PubMed Web of Science ®Google Scholar
• Hu L, Zaloudek C, Mills GB, et al. In vivo and in vitro ovarian carcinoma growth inhibition by a phosphatidylinositol 3-kinase inhibitor (LY294002). Clin Cancer Res. 2000;6:880–886.
   PubMed Web of Science ®Google Scholar
• Marone R, Cmiljanovic V, Giese B, et al. Targeting phosphoinositide 3-kinase: moving towards therapy. Biochim Biophys Acta. 2008;1784:159–185.
   PubMed Web of Science ®Google Scholar
• Ihle NT, Williams R, Chow S, et al. Molecular pharmacology and antitumor activity of PX-866, a novel inhibitor of phosphoinositide-3-kinase signaling. Mol Cancer Ther. 2004;3:763–772.
   PubMed Web of Science ®Google Scholar
• Boyle DL, Kim HR, Topolewski K, et al. Novel phosphoinositide 3-kinase delta, gamma inhibitor: potent anti-inflammatory effects and joint protection in models of rheumatoid arthritis. J Pharmacol Exp Ther. 2014;348:271–280.
   PubMed Web of Science ®Google Scholar
• Rommel C, Camps M, Ji H. PI3K delta and PI3K gamma: partners in crime in inflammation in rheumatoid arthritis and beyond?. Nat Rev Immunol. 2007;7:191–201.
   PubMed Web of Science ®Google Scholar
• Konrad S, Ali SR, Wiege K, et al. Phosphoinositide 3-kinases gamma and delta, linkers of coordinate C5a receptor-Fc-gamma receptor activation and immune complex-induced inflammation. J Biol Chem. 2008;283:33296–33303.
   PubMed Web of Science ®Google Scholar
• Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370:997–1007.
   PubMed Web of Science ®Google Scholar
• Lannutti BJ, Meadows SA, Herman SE, et al. CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood. 2011;117:591–594.
   PubMed Web of Science ®Google Scholar
• Meadows SA, Vega F, Kashishian A, et al. PI3Kdelta inhibitor, GS-1101 (CAL-101), attenuates pathway signaling, induces apoptosis, and overcomes signals from the microenvironment in cellular models of Hodgkin lymphoma. Blood. 2012;119:1897–1900.
   PubMed Web of Science ®Google Scholar
• Dong S, Guinn D, Dubovsky JA, et al. IPI-145 antagonizes intrinsic and extrinsic survival signals in chronic lymphocytic leukemia cells. Blood. 2014;124:3583–3586.
   PubMed Web of Science ®Google Scholar
• Balakrishnan K, Peluso M, Fu M, et al. The phosphoinositide-3-kinase (PI3K)-delta and gamma inhibitor, IPI-145 (duvelisib), overcomes signals from the PI3K/AKT/S6 pathway and promotes apoptosis in CLL. Leukemia. 2015;29:1811–1822.
   PubMed Web of Science ®Google Scholar
• Peluso M, Faia K, Winkler D, et al. Duvelisib (IPI-145) inhibits malignant b-cell proliferation and disrupts signaling from the tumor microenvironment through mechanisms that are dependent on PI3K-delta and PI3K-gamma. Blood. 2014;124.
   Web of Science ®Google Scholar
• Chen SS, Ham S, Rai KR, et al. Dual inhibition of PI3K-delta and gamma by duvelisib (IPI-145) impairs CLL B- and T-cell migration, survival and proliferation in a murine xenograft model using primary chronic lymphocytic leukemia cells. Blood. 2015;3(8):694–704.
   Google Scholar
• Porcu P, Flinn I, Kahl BS, et al. Clinical activity of duvelisib (IPI-145), a phosphoinositide-3-kinase-delta, gamma inhibitor, in patients previously treated with ibrutinib. Blood. 2014; 124.
   PubMed Web of Science ®Google Scholar
• O’Brien S, Patel M, Kahl BS, et al. Duvelisib (IPI-145), a PI3K-delta,gamma inhibitor, is clinically active in patients with relapsed/refractory chronic lymphocytic leukemia. Blood. 2014;124.
   Web of Science ®Google Scholar
• Horwitz SM, Porcu P, Flinn I, et al. Duvelisib (IPI-145), a phosphoinositide-3-kinase-delta,gamma inhibitor, shows activity in patients with relapsed/refractory T-cell lymphoma. Blood. 2014;124.
   PubMed Web of Science ®Google Scholar
• Flinn I, Oki Y, Patel M, et al. A phase 1 evaluation of duvelisib (IPI-145), a PI3K-delta,gamma inhibitor, in patients with relapsed/refractory iNHL. Blood. 2014;124.
   PubMed Web of Science ®Google Scholar
• E.K. MDP, Cutter K, Dietz LA, et al. A phase I trial of TGR-1202, a next generation once daily PI3K-delta inhibitor in combination with obinutuzumab plus chlorambucil, in patients with chronic lymphocytic leukemia. Blood. 2015;126.
   Web of Science ®Google Scholar
• 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)-9H-purin-6-amine (AMG319) and related PI3Kdelta inhibitors for inflammation and autoimmune disease. J Med Chem. 2015;58:480–511.
   PubMed Web of Science ®Google Scholar
• Shugg RP, Thomson A, Tanabe N, et al. Effects of isoform-selective phosphatidylinositol 3-kinase inhibitors on osteoclasts: actions on cytoskeletal organization, survival, and resorption. J Biol Chem. 2013;288:35346–35357.
   PubMed Web of Science ®Google Scholar
• Elster N, Cremona M, Morgan C, et al. A preclinical evaluation of the PI3K alpha/delta dominant inhibitor BAY 80-6946 in HER2-positive breast cancer models with acquired resistance to the HER2-targeted therapies trastuzumab and lapatinib. Breast Cancer Res Treat. 2015;149:373–383.
   PubMed Web of Science ®Google Scholar
• Scott WJ, Hentemann MF, Rowley RB, et al. Discovery and SAR of novel 2,3-dihydroimidazo[1,2-c]quinazoline PI3K inhibitors: identification of copanlisib (BAY 80-6946). ChemMedChem. 2016;11:1517–1530.
   PubMed Web of Science ®Google Scholar
• Okabe S, Tauchi T, Tanaka Y, et al. Anti-leukemic activity of phosphoinositide 3-kinase inhibitor, copanlisib in ABL tyrosine kinase resistant leukemia cells. Blood. 2014;124.
   Web of Science ®Google Scholar
• Brown JR, Davids MS, Rodon J, et al. Phase I trial of the pan-PI3K inhibitor pilaralisib (SAR245408/XL147) in patients with chronic lymphocytic leukemia (CLL) or relapsed/refractory lymphoma. Clin Cancer Res. 2015;21:3160–3169.
   PubMed Web of Science ®Google Scholar
• Matulonis U, Vergote I, Backes F, et al. Phase II study of the PI3K inhibitor pilaralisib (SAR245408; XL147) in patients with advanced or recurrent endometrial carcinoma. Gynecol Oncol. 2015;136:246–253.
   PubMed Web of Science ®Google Scholar
• Speranza MC, Nowicki MO, Behera P, et al. BKM-120 (buparlisib): a phosphatidyl-inositol-3 kinase inhibitor with anti-invasive properties in glioblastoma. Sci Rep. 2016;6:20189.
   PubMed Web of Science ®Google Scholar
• Vansteenkiste JF, Canon JL, Braud FD, et al. Safety and efficacy of buparlisib (BKM120) in patients with PI3K pathway-activated non-small cell lung cancer: results from the phase II BASALT-1 study. J Thorac Oncol. 2015;10:1319–1327.
   PubMed Web of Science ®Google Scholar
• Ando Y, Inada-Inoue M, Mitsuma A, et al. Phase I dose-escalation study of buparlisib (BKM120), an oral pan-class I PI3K inhibitor, in Japanese patients with advanced solid tumors. Cancer Sci. 2014;105:347–353.
   PubMed Web of Science ®Google Scholar
• Geuna E, Milani A, Martinello R, et al. Buparlisib, an oral pan-PI3K inhibitor for the treatment of breast cancer. Expert Opin Investig Drugs. 2015;24:421–431.
   PubMed Web of Science ®Google Scholar
• Thorpe LM, Yuzugullu H, Zhao JJ. PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting. Nat Rev Cancer. 2015;15:7–24.
   PubMed Web of Science ®Google Scholar
• Weigelt B, Warne PH, Lambros MB, et al. PI3K pathway dependencies in endometrioid endometrial cancer cell lines. Clin Cancer Res. 2013;19:3533–3544.
   PubMed Web of Science ®Google Scholar
• Bowles DW, Ma WW, Senzer N, et al. A multicenter phase 1 study of PX-866 in combination with docetaxel in patients with advanced solid tumours. Br J Cancer. 2013;109:1085–1092.
   PubMed Web of Science ®Google Scholar
• Levy B, Spira A, Becker D, et al. A randomized, phase 2 trial of docetaxel with or without PX-866, an irreversible oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or metastatic non-small-cell lung cancer. J Thorac Oncol. 2014;9:1031–1035.
   PubMed Web of Science ®Google Scholar
• Mayer IA, Abramson V, Formisano L, et al. A phase Ib study of alpelisib (BYL719), a PI3Kalpha-specific inhibitor, with letrozole in ER+/HER2-negative metastatic breast cancer. Clin Cancer Res. 2017;23:26–34.
   Web of Science ®Google Scholar
• Sarker D, Ang JE, Baird R, et al. First-in-human phase I study of pictilisib (GDC-0941), a potent pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, in patients with advanced solid tumors. Clin Cancer Res. 2015;21:77–86.
   PubMed Web of Science ®Google Scholar
• Hancox U, Cosulich S, Hanson L, et al. Inhibition of PI3Kbeta signaling with AZD8186 inhibits growth of PTEN-deficient breast and prostate tumors alone and in combination with docetaxel. Mol Cancer Ther. 2015;14:48–58.
   PubMed Web of Science ®Google Scholar
• Barlaam B, Cosulich S, Degorce S, et al. Discovery of (R)-8-(1-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chrom ene-6-carboxamide (AZD8186): a potent and selective inhibitor of PI3Kbeta and PI3Kdelta for the treatment of PTEN-deficient cancers. J Med Chem. 2015;58:943–962.
   PubMed Web of Science ®Google Scholar
• Yaguchi S, Fukui Y, Koshimizu I, et al. Antitumor activity of ZSTK474, a new phosphatidylinositol 3-kinase inhibitor. J Natl Cancer Inst. 2006;98:545–556.
   PubMed Web of Science ®Google Scholar
• Kong D, Yaguchi S, Yamori T. Effect of ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor, on DNA-dependent protein kinase. Biol Pharm Bull. 2009;32:297–300.
   PubMed Web of Science ®Google Scholar
• Kong D, Okamura M, Yoshimi H, et al. Antiangiogenic effect of ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor. Eur J Cancer. 2009;45:857–865.
   PubMed Web of Science ®Google Scholar
• Condliffe AM, Davidson K, Anderson KE, et al. Sequential activation of class IB and class IA PI3K is important for the primed respiratory burst of human but not murine neutrophils. Blood. 2005;106:1432–1440.
   PubMed Web of Science ®Google Scholar
• Knight ZA, Feldman ME, Balla A, et al. A membrane capture assay for lipid kinase activity. Nat Protoc. 2007;2:2459–2466.
   PubMed Web of Science ®Google Scholar
• Winkler DG, Faia KL, DiNitto JP, et al. PI3K-delta and PI3K-gamma inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013;20:1364–1374.
   PubMed Web of Science ®Google Scholar
• Camps M, Ruckle T, Ji H, et al. Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Nat Med. 2005;11:936–943.
   PubMed Web of Science ®Google Scholar
• Yang Q, Chen LS, Ha MJ, et al. Idelalisib impacts cell growth through inhibiting translation regulatory mechanisms in mantle cell lymphoma. Clin Cancer Res. 2016;23(1):181–192.
   PubMed Web of Science ®Google Scholar
• Dunbar J, Nevejans J, Mckee C, et al. Pharmacokinetics and pharmacodynamics of IPI-145, a potent inhibitor of phosphoinositide-3-kinase-delta,gamma, following single- and multiple-dose administration in healthy subjects and patients with advanced hematologic malignancies. Blood. 2012;120.
   Web of Science ®Google Scholar
• Flinn I, Patel M, Kahl BS, et al. Preliminary safety and efficacy of IPI-145, a potent inhibitor of phosphoinositide-3-kinase-delta,gamma, in patients with chronic lymphocytic leukemia. Blood. 2013; 122.
   Web of Science ®Google Scholar
• Flinn I, Miller CB, Ardeshna KM, et al. DYNAMO: A phase 2 study of duvelisib in subjects with refractory indolent non-Hodgkin lymphoma. Blood. 2016;128.
   PubMed Web of Science ®Google Scholar
• Compagno M, Wang Q, Pighi C, et al. Phosphatidylinositol 3-kinase delta blockade increases genomic instability in B cells. Nature. 2017 Feb 23;542(7642):489–493.
   PubMed Web of Science ®Google Scholar
• O’Brien SM, Lamanna N, Kipps TJ, et al. A phase 2 study of idelalisib plus rituximab in treatment-naive older patients with chronic lymphocytic leukemia. Blood. 2015 Dec 17;126(25):2686–2694.
   PubMed Web of Science ®Google Scholar
• Lampson BL, Kasar SN, Matos TR, et al. Idelalisib given front-line for treatment of chronic lymphocytic leukemia causes frequent immune-mediated hepatotoxicity. Blood. 2016 Jul 14;128(2):195–203.
   PubMed Web of Science ®Google Scholar
• Evans CA, Liu T, Lescarbeau A, et al. Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate.ACS Med Chem Lett. 2016 Jul 22;7(9):862–867.
   Google Scholar
• Patel VM, Balakrishnan K, Douglas M, et al. Duvelisib treatment is associated with altered expression of apoptotic regulators that helps in sensitization of chronic lymphocytic leukemia cells to venetoclax (ABT-199). Leukemia; [cited 2017 Feb 3]. doi: 10.1038/leu.2016.382.
   Google Scholar
• Thijssen R, Ter BJ, Gg VB, et al. The pan phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor SAR245409 (voxtalisib/XL765) blocks survival, adhesion and proliferation of primary chronic lymphocytic leukemia cells. Leukemia. 2016 Sep;30(9):1963.
   PubMed Web of Science ®Google Scholar