Table 1.

A summary of PI3K/AKT/mTOR pathway inhibitors in clinical development

Agent (company)TargetPhaseaTumor types currently under investigationa
Everolimus (Novartis)mTORC1ApprovedApproved for the treatment of renal cell carcinoma, subependymal giant cell astrocytoma associated with tuberous sclerosis, pancreatic neuroendocrine tumors, and ER+ breast cancer (in combination with exemestane)
Temsirolimus (Pfizer)mTORC1ApprovedApproved for the treatment of renal cell carcinoma
BEZ235 (Novartis)PI3K/mTORPhase IIAdvanced solid tumors, breast cancer, castration-resistant prostate cancer, renal cell carcinoma, leukemias, pancreatic neuroendocrine tumors, urothelial transitional cell carcinoma
GDC-0980 (Genentech)PI3K/mTORPhase IISolid cancers, non-Hodgkin lymphoma, breast cancer, prostate cancer
PF-05212384 (Pfizer)PI3K/mTORPhase I/IIAdvanced solid tumors, colorectal cancer, endometrial neoplasms
SAR245409 (XL-765; Sanofi/Exelixis)PI3K/mTORPhase IIAdvanced solid tumors, CLL, indolent non-Hodgkin lymphoma, mantle cell lymphoma, ovarian cancer
BAY80-6946 (Bayer)Pan-class I PI3KPhase IIAdvanced solid tumors, non-Hodgkin lymphoma
Buparlisib (BKM120; Novartis)Pan-class I PI3KPhase IVAdvanced solid tumors, breast cancer (ER+, HER2+, and HER2−), cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, GIST, glioblastoma, head & neck neoplasms, leukemias and lymphomas, melanoma, NSCLC, ovarian cancer, prostate cancer, renal cell carcinoma, urothelial transitional cell cancer
Pictilisib (GDC-0941; Genentech)Pan-class I PI3KPhase IIBreast cancer, NSCLC
PX-866 (Oncothyreon)Pan-class I PI3KPhase IIAdvanced BRAF-mutant cancers, NSCLC, prostate cancer
SAR245408 (XL-147; Sanofi/Exelixis)Pan-class I PI3KPhase I/IIAdvanced solid tumors
ZSTK474 (Zenyaku Kogyo)Pan-class I PI3KPhase I/IIAdvanced solid tumors
BYL719 (Novartis)PI3K p110αPhase IIAdvanced solid tumors (including those with PIK3CA alteration), breast cancer, colorectal cancer, esophageal cancer, gastrointestinal cancer, GIST, head & neck squamous cell cancer
GDC-0032 (Genentech)PI3K p110α, δ, and γ inhibitorPhase IAdvanced solid tumors and metastatic breast cancer (ER+)
MLN01117 (INK1117; Intellikine)PI3K p110αPhase IAdvanced solid tumors with PIK3CA mutation
GSK2636771 (GSK)PI3K p110βPhase IAdvanced solid tumors with PTEN deficiency
SAR260301 (Sanofi)PI3K p110βPhase IAdvanced solid tumors
Idelalisib (CAL-101; GS-1101; Gilead/Calistoga)PI3K p110δPhase IIICLL, lymphomas
AMG319 (Amgen)PI3K p110δPhase IHematologic malignancies
Perifosine (KRX-0401; Keryx)AKTPhase I/IIAdvanced solid tumors, multiple myeloma
MK2206 (Merck)AKTPhase IIAdvanced solid tumors, breast cancer, colorectal cancer, endometrial cancer, head & neck cancer, lung cancer, lymphomas, pancreatic cancer, prostate cancer
GDC-0068 (Genentech)AKTPhase IIAdvanced solid tumors, gastric cancer, prostate cancer
GSK2110183 (GSK)AKTPhase IIAdvanced solid tumors, CLL, multiple myeloma, ovarian cancer
GSK2141795 (GSK)AKTPhase IIAdvanced solid tumors, breast cancer, cervical cancer, endometrial cancer, leukemias, melanoma, multiple myeloma
ARQ 092 (ArQule/Daiichi Sankyo)AKTPhase IAdvanced solid tumors
AZD5363 (AstraZeneca)AKTPhase I/IIAdvanced solid tumors, breast cancer, prostate cancer
AZD2014 (AstraZeneca)mTORC1/2Phase IIAdvanced solid tumors, breast cancer, renal cell carcinoma
MLN0128 (INK128; Intellikine)mTORC1/2Phase IAdvanced solid tumors, hematologic malignancies
CC-223 (Celgene)mTORC1/2Phase I/IIBreast cancer, glioblastoma, hematologic malignancies, liver cancer, NSCLC, neuroendocrine tumors

Abbreviations: CLL, chronic lymphocytic leukemia; ER+, estrogen receptor–positive; GIST, gastrointestinal stromal tumor; NSCLC, non–small cell lung cancer.

  • aPhase of development, based on trials that were listed in as enrolling patients, or yet to be enrolling patients, as of November 2013.