Table 2

List of PI3K pathway inhibitors currently undergoing clinical development for pancreatic cancer

TargetInhibitorPhaseStatusPatientsCombinationNIH numberReference(s)
Akt inhibitors
 Pan-AktMK2206ICompletedAdvST/MST
(~9% pancreatic cancer)
MonotherapyNCT00670488 262 263
ICompletedAdvST/MSTSelumitinib (MEKi)NCT01021748
ICompletedPDAC (PTEN loss)MonotherapyNCT00848718 264
ICompletedPancreatic cancerDinaciclib (CDKi)NCT01783171
IICompletedPancreatic cancerSelumitinib (MEKi)
versus mFOLFOX6
NCT01658943 265
Afuresertib (GSK2110183)ICompletedAdvST
(21% pancreatic cancer)
Trametinib (MEKi)NCT01476137 266
IIOngoingAdvSTNCT01531894
Uprosertib (GSK2141795)ICompletedPancreatic cancerTrametinib (MEKi)NCT01138085
ICompletedAdvSTNCT00920257
Oleandrin (PBI-05204)ICompletedAdvST
(6% pancreatic cancer)
NCT00554268 267
IIOngoingMetastatic pancreatic cancerNCT02329717
PerifosineIICompletedLocally advanced or metastatic pancreatic cancerNCT00053924
IICompletedLocally advanced or metastatic pancreatic cancerNCT00059982 268
RX-0201IICompletedMetastatic pancreatic cancerGemcitabineNCT01028495
Rapalogs
 mTORC1 (FKBP12)Sirolimus (rapamycin)ICompletedPancreatic cancerSunitinib (RTKi)NCT00583063 150
ICompletedPancreatic cancerSorafenib (RTKi)NCT00449280 150
IICompletedPancreatic cancerNCT00499486
IICompletedPancreatic cancerNCT00276744
I/IIOngoingPDACMetforminNCT02048384
IOngoingPancreatic cancerVismodegib (SMOi)NCT01537107
Temsirolimus (CCI-779, Torisel)ICompletedPancreatic cancerLenalidomideNCT01183663
ITerminatedPDACGemcitabineNCT00593008
I/IIOngoingPancreatic cancerNivolumab (PD-1i)NCT02423954
IICompletedLocally advanced or metastatic pancreatic cancerNCT00075647 95
Everolimus (RAD001)ICompletedPancreatic cancerSorafenib (RTKi)NCT00981162
ICompletedPancreatic cancerTrametinib (MEKi)NCT00955773 269
I/IICompletedPDACGemcitabineNCT00560963
I/IICompletedPancreatic cancerCetuximab (EGFRi) and capecitabineNCT01077986 99
IITerminatedPancreatic cancerErlotinib (EGFRi)NCT00640978 95
IICompletedPancreatic cancerNCT00409292 94
I/IIRecruitingPDACRibociclib (CDKi)NCT02985125
RidafirolimusICompletedAdvST
(12% pancreatic cancer)
Bevacizumab (VEGFRi)NCT00781846 149
PI3K inhibitors
 PI3K isoform p110αAlpelisib (BYL719)IOngoingPancreatic cancerGemcitabine and abraxaneNCT02155088
 Pan-PI3KBuparlisib (BKM120)ICompletedPancreatic cancermFOLFOX6NCT01571024 270
ICompletedPancreatic cancerLDE225 (SMOi)NCT01576666
ICompletedPancreatic cancerTrametinib (MEKi)NCT01155453 271
IOngoingAdvSTMEK163 (MEKi)NCT01363232
PX-866ICompletedAdvST
(5% PDAC)
DocetaxelNCT01204099 272
ZSTK474ICompletedAdvSTNCT01280487
Copanlisib
(BAY 80–6946)
ICompletedAdvST
(18% pancreatic cancer)
NCT00962611 273
Dual PI3K pathway inhibitors
 mTORC1/2Vistusertib (AZD2014)ICompletedAdvSTNCT01026402 98
IIRecruitingAdvST (RICTOR amplified)NCT03166904
IIRecruitingAdvST:
combination with Selumitinib (MEKi)
NCT02583542
IIRecruitingAdvST (TSC1/2 loss or mutation)NCT03166176
IIRecruitingAdvST:
combination with Olaparib (PARPi)
NCT02576444
 p70-S6K and AktLY2780301ICompleteAdvST
(~22% pancreatic cancer)
NCT01115751 274
 PI3K and mTORDactolisib
(NVP-BEZ235)
ICompletedAdvSTMEK162 (MEKi)NCT01337765
NVP-BGT226ICompletedAdvST
(2% pancreatic cancer)
NCT00600275 275
Voxtalisib (SAR245409, XL765)ICompletedAdvST
(4% pancreatic cancer)
NCT00485719 276
SF1126
(LY294002 prodrug)
ICompletedAdvST
(5% pancreatic cancer)
NCT00907205 277
Gedatolisib (PF-05212384, PKI-587)ITerminatedAdvST
(5% pancreatic cancer)
IrinotecanNCT01347866 278
ICompletedAdvST
(4% PDAC)
NCT00940498 279
IRecruitingAdvSTPalbociclib (CDKi)NCT03065062
  • AdvST, advanced solid tumours (including pancreatic cancer); CDKi, cyclin-dependent kinase inhibitor; EGFR, epidermal growth factor receptor; EGFRi, EGFR inhibitor; MEKi, MAPK/ERK kinase inhibitor inhibitor; mFOLFOX6, modified FOLFOX (ie, 5-fluorouracil and oxaliplatin); MST, metastatic solid tumours (including pancreatic cancer); mTOR, mechanistic target of rapamycin; NIH, National Institutes of Health; PARP, poly (ADP-ribose) polymerase; PARPi, PARP inhibitors; PDAC, pancreatic ductal adenocarcinoma; PD-1, programmed death-1; PD-1i, PD-1 inhibitor; PI3K, phosphoinositide 3-kinase; RTKi, receptor tyrosine kinase inhibitor; SMOi, smoothened inhibitor; VEGFRi, vascular endothelial growth factor receptor inhibitor.