T790M |
Covalent EGFR-TKI inhibitor |
Afatinib |
LUX-lung 1 [78], LUX-lung 2 [163], LUX-lung 3 [80], LUX-lung 4 [79], LUX-lung 6 [81] |
NCT01085136, NCT01466660, NCT01523587
|
T790M-selective inhibitor |
CO-1686, PKC412, AZD9291 |
Phase I studies of PKC412 [89,164] |
NCT01526928, NCT02147990 (TIGER-2), NCT01802632 (AURA), NCT02094261 (AURA2) |
HGF |
HGF antagonist |
NK4 |
|
|
Anti-HGF antibody |
TAK-701, ficlatuzumab |
Phase I study of TAK 701 [94] |
NCT01039948 |
Phase II trial comparing gefitinib with and without ficlatuzumab [165] |
MET |
MET tyrosine kinase inhibitors |
Tivantinib, cabozantinib, INC280 |
Phase II study comparing erlotinib with or without tivantinib [97] |
NCT01580735, NCT02049060, NCT01377376, NCT00596648, NCT01866410, NCT01639508, NCT01610336
|
Phase III study comparing erlotinib with and without tivantinib [29] |
MET mono-antibody |
Onartuzumab |
phase II trial comparing erlotinib with and without onartuzumab [166] |
NCT01456325 (MetLung) NCT01887886, NCT02031744
|
HER3 |
Anti-HER3 agents |
Pertuzumab |
Phase II study exploring pertuzumab plus erlotinib [107] |
|
HER2 |
Anti-HER2 agents |
Lapatinib, trastuzumab, neratinib |
Phase II trial evaluating lapatinib as monotherapy [167] |
NCT01827267, NCT01184482, NCT01306045, NCT00004883, NCT00758134, NCT01827267, NCT00266877
|
Phase II trial evaluating neratinib [168] |
IGF-1R |
IGF-1R mono-antibody |
R1507 |
Phase II study exploring erlotinib plus placebo or R1507 [169] |
NCT00773383 |
PI3K |
PI3K inhibitors |
BAY 80-6946, LY294002 |
|
NCT01460537, NCT01411410, NCT01404390, NCT00962611
|
mTOR |
mTORC1 inhibitors |
Everolimus, temsirolimus, sirolimus |
Phase II exploring everolimus plus gefitinib [111] |
NCT00079235, NCT01827267, NCT01737502, NCT01050985, NCT01482156
|
Phase II study of temsirolimus monotherapy [170] |
Dual PI3K/mTOR inhibitors |
BEZ235, PF-04691502, PKI-402 |
Phase I study of PF-04691502 monotherapy [122] |
NCT01482156, NCT00620594, NCT01343498, NCT01508104
|
AKT |
AKT inhibitors |
MK-2206, Enzastaurin, |
Phase I trial exploring MK-2206 plus carboplatin/paclitaxel, docetaxel or erlotinib [124] |
NCT01147211, NCT01294306, NCT00452413
|
Phase I trials exploring enzastaurin plus gemcitabine/cisplatinin [126] |
Phase II study, exploring enzastaurin plus cisplatin/pemetrexed [127] |
HSP90 |
Hsp90 inhibitors |
Ganetespib, AUY-922, DS-2248, retaspimycin, 17-DMAG |
Phase II study evaluating IPI-504 monotherapy [140] |
NCT01348126, NCT01031225, NCT01259089, NCT01784640, NCT01288430, NCT01362400, NCT01427946
|
Phase II study evaluating ganetespib monotherapy [141] |