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Table 2 A selection of PI3K/mTOR/AKT inhibitors in clinical development for acute leukemia with a brief summary of preclinical or clinical data

From: Outlook on PI3K/AKT/mTOR inhibition in acute leukemia

PI3K/AKT/mTOR inhibitors in clinical development
Compound Target Disease/ Model Result Reference
Buparlisib (BKM120) pan PI3K AML 1 of 11 responded lasting 80 days Naval, LaKeisha et al., EHA Annual Meeting, 2014 [107]
  pan PI3K T-ALL murine model decreased leukemic activity Lonetti, Antunes et al., Leukemia, 2014 [109]
BYL719 PI3K-α AML murine model decreased colony forming units in leukemia cells Gritsman, Yuzugullu et al., J Clin Invest, 2014 [22]
BYL719 + MEKi PI3K-α AML phase IB, ongoing ClinicalTrials.gov Identifier: NCT01449058
BAY 80-6946 PI3K-δ and PI3K-α NHL phase II, ORR 40/67/83/50% in FL/CLL/MCL/PTCL Dreyling, Morschhauser et al., ASH Annual Meeting 2013 [130]
ONC-01910 (rigosertib) PI3K-α and PI3K-β B-cell malignancies phase I, ORR 0%, SD in 7 (50%) of 14 patients Roschewski, Farooqui et al., Leukemia 2013 [131]
  PI3K-α and PI3K-β MDS phase I/II, CR in 4 (31%) of 13, SD in 8 (62%) of 13 Seetharam, Fan et al., Leuk Res, 2012 [126]
  PI3K-α and PI3K-β MDS phase I, ORR 6 (16%) of 37 patients Komrokji, Raza et al., Br J Haematol, 2013 [132]
C87114 PI3Kδ AML, initial diagnosis inhibited proliferation in vitro; in combination with etoposide Billottet, Grandage et al., Oncogene, 2006 [24]
CAL-101 (Idelalisib) PI3Kδ AML in vitro 1 of 31 AML responded Lanutti, Meadows et al., Blood, 2011 [98]
  PI3Kδ B-ALL in vitro 5 of 22 responded Lanutti, Meadows et al., Blood, 2011 [98]
  PI3Kδ B-CLL phase III, ORR 81% Furman, Sharman et al., NEJM, 2014 [93]
  PI3Kδ indolent B-NHL phase II, ORR 71 (57%) of 125 Gopal, Kahl et al., NEJM, 2014 [94]
CAL-130 PI3Kδ/γ T-ALL murine model prolonged survival Subramaniam, Whye et al., Cancer Cell, 2012 [55]
IPI-145 PI3Kδ/γ T-ALL cell line induction of apoptosis in vitro Huang, Proctor et al., ASH Annual Meeting, 2013 [99]
KP372-1 pan-PI3K/mTOR AML induction of apotosis in vitro Zeng, Samudio et al., Cancer Res, 2006 [133]
PI-103 pan-PI3K/mTOR T-ALL cell lines inhibited proliferation in 15/15, induced apoptosis in 3/15 Shephard, Banerjee et al., Leukemia, 2013 [117]
  pan-PI3K/mTOR T-ALL derived lymphoblasts in vitro 7 of 7 responded Chiarini, Fala, Cancer Res, 2009 [116]
BEZ235 pan-PI3K/mTOR AML phase I, ORR 0 (0%) of 11 patients, SD 1 (9%) of 11 patients Wunderle, Badura et al., ASH annual meeting, 2013 [111]
  pan-PI3K/mTOR ALL phase I, ORR 3 (33%) of 9 patients Wunderle, Badura et al., ASH annual meeting, 2013 [111]
Perifosine AKT CLL phase II, ORR 1 (12,5%) of 8, SD 6 (75%) of 8 patients Friedman, Lanasa et al., Leuk Lymphoma, 2014 [134]
Perifosine + UCN-01 AKT AML phase I, ORR 0 (0%) of 11 patients Gojo, Perl et al., Invest New Drugs, 2013 [90]
GSK2141795 + MEK inhibitor AKT1/2/3 several cancer types in vitro efficacy in cell lines and murine models Dumble, Crouthamel et al., PLOS One, 2014 [135]
GSK2141795 + Trametinib AKT1/2/3 AML phase II, ongoing ClinicalTrials.gov Identifier: NCT01907815
MK-2206 AKT1 ALL Reversal of glucocorticoid resistance in vitro and in vivo Piovan, Yu et al., Cancer Cell, 2013 [52]
Triciribine (API-2) AKT AML ORR 17 (53%) of 32, but no CR/PR Sampath, Malik et al., Leuk Res, 2013 [91]
GSK690693 pan AKT ALL in vitro inhibition of proliferation and induction of apoptosis Levy, Kahana et al., Blood, 2009 [136]
Sirolimus mTORC1 AML ORR monotherapy 4 (44%) of 9 Recher, Beyne-Rauzy, Blood, 2005 [31]
  mTORC2 AML phase I, 6 (27%) of 27 combined with MEC Perl, Kasner et al., Clin Cancer Res, 2009 [77]
Everolimus mTORC2 B-ALL phase I/II, ORR 7 (35%) of 20 Daver, Kantarjian et al., ASH annual meeting, 2013 [81]
Everolimus + chemotherapy mTORC1 AML phase Ib, 19 (68%) of 28 patients Park, Chapuis et al., Leukemia, 2013 [33]
Temsirolimus mTORC1 AML phase II, ORR 11 (21%) of 53 patients Amadori, Stasi et al., Br J Haematol, 2011 [79]