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

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]