Table 2.
List of PI3K pathway inhibitors currently undergoing clinical development for pancreatic cancer
| Target | Inhibitor | Phase | Status | Patients | Combination | NIH number | Reference(s) |
| Akt inhibitors | |||||||
| Pan-Akt | MK2206 | I | Completed | AdvST/MST (~9% pancreatic cancer) |
Monotherapy | NCT00670488 | 262 263 |
| I | Completed | AdvST/MST | Selumitinib (MEKi) | NCT01021748 | |||
| I | Completed | PDAC (PTEN loss) | Monotherapy | NCT00848718 | 264 | ||
| I | Completed | Pancreatic cancer | Dinaciclib (CDKi) | NCT01783171 | |||
| II | Completed | Pancreatic cancer | Selumitinib (MEKi) versus mFOLFOX6 |
NCT01658943 | 265 | ||
| Afuresertib (GSK2110183) | I | Completed | AdvST (21% pancreatic cancer) |
Trametinib (MEKi) | NCT01476137 | 266 | |
| II | Ongoing | AdvST | NCT01531894 | ||||
| Uprosertib (GSK2141795) | I | Completed | Pancreatic cancer | Trametinib (MEKi) | NCT01138085 | ||
| I | Completed | AdvST | NCT00920257 | ||||
| Oleandrin (PBI-05204) | I | Completed | AdvST (6% pancreatic cancer) |
NCT00554268 | 267 | ||
| II | Ongoing | Metastatic pancreatic cancer | NCT02329717 | ||||
| Perifosine | II | Completed | Locally advanced or metastatic pancreatic cancer | NCT00053924 | |||
| II | Completed | Locally advanced or metastatic pancreatic cancer | NCT00059982 | 268 | |||
| RX-0201 | II | Completed | Metastatic pancreatic cancer | Gemcitabine | NCT01028495 | ||
| Rapalogs | |||||||
| mTORC1 (FKBP12) | Sirolimus (rapamycin) | I | Completed | Pancreatic cancer | Sunitinib (RTKi) | NCT00583063 | 150 |
| I | Completed | Pancreatic cancer | Sorafenib (RTKi) | NCT00449280 | 150 | ||
| II | Completed | Pancreatic cancer | NCT00499486 | ||||
| II | Completed | Pancreatic cancer | NCT00276744 | ||||
| I/II | Ongoing | PDAC | Metformin | NCT02048384 | |||
| I | Ongoing | Pancreatic cancer | Vismodegib (SMOi) | NCT01537107 | |||
| Temsirolimus (CCI-779, Torisel) | I | Completed | Pancreatic cancer | Lenalidomide | NCT01183663 | ||
| I | Terminated | PDAC | Gemcitabine | NCT00593008 | |||
| I/II | Ongoing | Pancreatic cancer | Nivolumab (PD-1i) | NCT02423954 | |||
| II | Completed | Locally advanced or metastatic pancreatic cancer | NCT00075647 | 95 | |||
| Everolimus (RAD001) | I | Completed | Pancreatic cancer | Sorafenib (RTKi) | NCT00981162 | ||
| I | Completed | Pancreatic cancer | Trametinib (MEKi) | NCT00955773 | 269 | ||
| I/II | Completed | PDAC | Gemcitabine | NCT00560963 | |||
| I/II | Completed | Pancreatic cancer | Cetuximab (EGFRi) and capecitabine | NCT01077986 | 99 | ||
| II | Terminated | Pancreatic cancer | Erlotinib (EGFRi) | NCT00640978 | 95 | ||
| II | Completed | Pancreatic cancer | NCT00409292 | 94 | |||
| I/II | Recruiting | PDAC | Ribociclib (CDKi) | NCT02985125 | |||
| Ridafirolimus | I | Completed | AdvST (12% pancreatic cancer) |
Bevacizumab (VEGFRi) | NCT00781846 | 149 | |
| PI3K inhibitors | |||||||
| PI3K isoform p110α | Alpelisib (BYL719) | I | Ongoing | Pancreatic cancer | Gemcitabine and abraxane | NCT02155088 | |
| Pan-PI3K | Buparlisib (BKM120) | I | Completed | Pancreatic cancer | mFOLFOX6 | NCT01571024 | 270 |
| I | Completed | Pancreatic cancer | LDE225 (SMOi) | NCT01576666 | |||
| I | Completed | Pancreatic cancer | Trametinib (MEKi) | NCT01155453 | 271 | ||
| I | Ongoing | AdvST | MEK163 (MEKi) | NCT01363232 | |||
| PX-866 | I | Completed | AdvST (5% PDAC) |
Docetaxel | NCT01204099 | 272 | |
| ZSTK474 | I | Completed | AdvST | NCT01280487 | |||
| Copanlisib (BAY 80–6946) |
I | Completed | AdvST (18% pancreatic cancer) |
NCT00962611 | 273 | ||
| Dual PI3K pathway inhibitors | |||||||
| mTORC1/2 | Vistusertib (AZD2014) | I | Completed | AdvST | NCT01026402 | 98 | |
| II | Recruiting | AdvST (RICTOR amplified) | NCT03166904 | ||||
| II | Recruiting | AdvST: combination with Selumitinib (MEKi) |
NCT02583542 | ||||
| II | Recruiting | AdvST (TSC1/2 loss or mutation) | NCT03166176 | ||||
| II | Recruiting | AdvST: combination with Olaparib (PARPi) |
NCT02576444 | ||||
| p70-S6K and Akt | LY2780301 | I | Complete | AdvST (~22% pancreatic cancer) |
NCT01115751 | 274 | |
| PI3K and mTOR | Dactolisib (NVP-BEZ235) |
I | Completed | AdvST | MEK162 (MEKi) | NCT01337765 | |
| NVP-BGT226 | I | Completed | AdvST (2% pancreatic cancer) |
NCT00600275 | 275 | ||
| Voxtalisib (SAR245409, XL765) | I | Completed | AdvST (4% pancreatic cancer) |
NCT00485719 | 276 | ||
| SF1126 (LY294002 prodrug) |
I | Completed | AdvST (5% pancreatic cancer) |
NCT00907205 | 277 | ||
| Gedatolisib (PF-05212384, PKI-587) | I | Terminated | AdvST (5% pancreatic cancer) |
Irinotecan | NCT01347866 | 278 | |
| I | Completed | AdvST (4% PDAC) |
NCT00940498 | 279 | |||
| I | Recruiting | AdvST | Palbociclib (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.