Results of an abbreviated phase II study of AKT inhibitor MK-2206 in the treatment of recurrent platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal carcinoma (NCT 01283035)

Elizabeth K. Lee; Zhenying Tan-Wasielewski; Carol Aghajanian; Robert L. Coleman; Jennifer Curtis; Michelle S. Hirsch; Ursula A. Matulonis; Lewis C. Cantley; Gordon B. Mills; L. Austin Doyle; Joyce F. Liu

doi:10.1016/j.gore.2020.100546

Results of an abbreviated phase II study of AKT inhibitor MK-2206 in the treatment of recurrent platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal carcinoma (NCT 01283035)

Elizabeth K. Lee, Zhenying Tan-Wasielewski, Carol Aghajanian, Robert L. Coleman, Jennifer Curtis, Michelle S. Hirsch, Ursula A. Matulonis, Lewis C. Cantley, Gordon B. Mills, L. Austin Doyle, Joyce F. Liu

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Platinum-resistant, recurrent, high grade epithelial ovarian carcinoma remains challenging to treat. Chemotherapy produces limited responses with modest survival benefits in the treatment of recurrent disease. In this context, targeted therapies may improve upon conventional therapies. PI3K/AKT pathway alterations are frequently found in several cancer types, including ovarian cancer, and thus AKT inhibition is a rational targeted therapy. Here we report the results of an abbreviated trial of AKT inhibitor MK-2206 in platinum resistant high grade serous ovarian, fallopian tube, and primary peritoneal cancer with PTEN loss.

Original language	English (US)
Article number	100546
Journal	Gynecologic Oncology Reports
Volume	32
DOIs	https://doi.org/10.1016/j.gore.2020.100546
State	Published - May 2020
Externally published	Yes

Keywords

AKT inhibitor
MK-2206
PI3K/AKT pathway
PTEN
Platinum resistant ovarian cancer
Serous ovarian carcinoma

ASJC Scopus subject areas

Oncology
Obstetrics and Gynecology

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Lee, E. K., Tan-Wasielewski, Z., Aghajanian, C., Coleman, R. L., Curtis, J., Hirsch, M. S., Matulonis, U. A., Cantley, L. C., Mills, G. B., Doyle, L. A., & Liu, J. F. (2020). Results of an abbreviated phase II study of AKT inhibitor MK-2206 in the treatment of recurrent platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal carcinoma (NCT 01283035). Gynecologic Oncology Reports, 32, [100546]. https://doi.org/10.1016/j.gore.2020.100546

Results of an abbreviated phase II study of AKT inhibitor MK-2206 in the treatment of recurrent platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal carcinoma (NCT 01283035). / Lee, Elizabeth K.; Tan-Wasielewski, Zhenying; Aghajanian, Carol; Coleman, Robert L.; Curtis, Jennifer; Hirsch, Michelle S.; Matulonis, Ursula A.; Cantley, Lewis C.; Mills, Gordon B.; Doyle, L. Austin; Liu, Joyce F.

In: Gynecologic Oncology Reports, Vol. 32, 100546, 05.2020.

Research output: Contribution to journal › Article › peer-review

Lee, EK, Tan-Wasielewski, Z, Aghajanian, C, Coleman, RL, Curtis, J, Hirsch, MS, Matulonis, UA, Cantley, LC, Mills, GB, Doyle, LA & Liu, JF 2020, 'Results of an abbreviated phase II study of AKT inhibitor MK-2206 in the treatment of recurrent platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal carcinoma (NCT 01283035)', Gynecologic Oncology Reports, vol. 32, 100546. https://doi.org/10.1016/j.gore.2020.100546

Lee EK, Tan-Wasielewski Z, Aghajanian C, Coleman RL, Curtis J, Hirsch MS et al. Results of an abbreviated phase II study of AKT inhibitor MK-2206 in the treatment of recurrent platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal carcinoma (NCT 01283035). Gynecologic Oncology Reports. 2020 May;32. 100546. https://doi.org/10.1016/j.gore.2020.100546

Lee, Elizabeth K. ; Tan-Wasielewski, Zhenying ; Aghajanian, Carol ; Coleman, Robert L. ; Curtis, Jennifer ; Hirsch, Michelle S. ; Matulonis, Ursula A. ; Cantley, Lewis C. ; Mills, Gordon B. ; Doyle, L. Austin ; Liu, Joyce F. / Results of an abbreviated phase II study of AKT inhibitor MK-2206 in the treatment of recurrent platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal carcinoma (NCT 01283035). In: Gynecologic Oncology Reports. 2020 ; Vol. 32.

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title = "Results of an abbreviated phase II study of AKT inhibitor MK-2206 in the treatment of recurrent platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal carcinoma (NCT 01283035)",

abstract = "Platinum-resistant, recurrent, high grade epithelial ovarian carcinoma remains challenging to treat. Chemotherapy produces limited responses with modest survival benefits in the treatment of recurrent disease. In this context, targeted therapies may improve upon conventional therapies. PI3K/AKT pathway alterations are frequently found in several cancer types, including ovarian cancer, and thus AKT inhibition is a rational targeted therapy. Here we report the results of an abbreviated trial of AKT inhibitor MK-2206 in platinum resistant high grade serous ovarian, fallopian tube, and primary peritoneal cancer with PTEN loss.",

keywords = "AKT inhibitor, MK-2206, PI3K/AKT pathway, PTEN, Platinum resistant ovarian cancer, Serous ovarian carcinoma",

author = "Lee, {Elizabeth K.} and Zhenying Tan-Wasielewski and Carol Aghajanian and Coleman, {Robert L.} and Jennifer Curtis and Hirsch, {Michelle S.} and Matulonis, {Ursula A.} and Cantley, {Lewis C.} and Mills, {Gordon B.} and Doyle, {L. Austin} and Liu, {Joyce F.}",

note = "Funding Information: GBM is an advisory board member with AstraZeneca, ImmunoMET, Ionis, Nuevolution, PDX bio, Signalchem, Symphogen, and Tarveda, has stock options with Catena Pharmaceuticals, ImmunoMet, SignalChem, Spindle Top Ventures and Tarveda, travel support from Chrysallis Bio, and has licensed technology to Nanostring and Myriad Genetics. GBM is supported by a kind gift from the Miriam and Sheldon Adelson Medical Research Foundation , the Ovarian Cancer Research Foundation , The Breast Cancer Research Foundation , Prospect Creek Foundation , The Komen Foundation SAC110052 , and NCI grants: CA217685 , CA217842 , and CA098258 . Funding Information: LCC owns equity in, receives compensation from, and serves on the scientific advisory board of Agios Pharmaceuticals. He is also a founder of and receives laboratory support from Petra Pharmaceuticals and receives compensation for being on the scientific advisory board of Petra Pharmaceuticals. No drugs from these companies were involved in this study. LCC reports support through the National Cancer Institute of the National Institutes of Health under Award Number R35CA197588 , and through a Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (Grant number: SU2C-AACR-DT22-17 ). Additionally he reports personal fees and other from Cell Signaling Technology and Sanofi USA, grants and personal fees from Pfizer, personal fees from Novo Nordisk, other from Volastra, EIP Pharma, and Faeth, outside the submitted work. In addition, Dr. Cantley has a patent US8883438 licensed to Agios Pharmaceuticals, a patent US8715665 licensed to BIDMC, a patent US5532167 licensed to BIDMC, a patent US8552050 licensed to BIDMC, a patent US6004757 licensed to BIDMC, a patent US9493813 licensed to BIDMC, a patent US9745631 licensed to BIDMC, a patent US9119858 licensed to GENESYS RESEARCH INSTITUTE, a patent US10138479 licensed to BIDMC, a patent US6462173 licensed to CLEAR-COAT HOLDING, a patent US8877791 licensed to BIDMC, a patent US20190010144A1 licensed to Cornell University, California Institute of Biological Research, a patent US20170073760A1 pending to BIDMC, and a patent US20190136238A1 pending to BIDMC. Funding Information: CA reports personal fees from Tesaro, Immunogen, Eisai / Merck , and Mateon Therapeutics, grants and personal fees from Clovis, and grants from Genentech , AbbVie , and Astra Zeneca, outside the submitted work. Funding Information: This work was funded by a Stand Up to Cancer Dream Team Translational Research Grant, a Program of the Entertainment Industry Foundation ( SU2C-AACR-DT0209 ). Research grants are administered by the American Association for Cancer Research , the scientific partner of SU2C. The study was sponsored by the National Cancer Institute under the Cancer Therapy Evaluation Program. Funding Information: This work was funded by a Stand Up to Cancer Dream Team Translational Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-DT0209). Research grants are administered by the American Association for Cancer Research, the scientific partner of SU2C. The study was sponsored by the National Cancer Institute under the Cancer Therapy Evaluation Program.GBM is an advisory board member with AstraZeneca, ImmunoMET, Ionis, Nuevolution, PDX bio, Signalchem, Symphogen, and Tarveda, has stock options with Catena Pharmaceuticals, ImmunoMet, SignalChem, Spindle Top Ventures and Tarveda, travel support from Chrysallis Bio, and has licensed technology to Nanostring and Myriad Genetics. GBM is supported by a kind gift from the Miriam and Sheldon Adelson Medical Research Foundation, the Ovarian Cancer Research Foundation, The Breast Cancer Research Foundation, Prospect Creek Foundation, The Komen Foundation SAC110052, and NCI grants: CA217685, CA217842, and CA098258.LCC owns equity in, receives compensation from, and serves on the scientific advisory board of Agios Pharmaceuticals. He is also a founder of and receives laboratory support from Petra Pharmaceuticals and receives compensation for being on the scientific advisory board of Petra Pharmaceuticals. No drugs from these companies were involved in this study. LCC reports support through the National Cancer Institute of the National Institutes of Health under Award Number R35CA197588, and through a Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (Grant number: SU2C-AACR-DT22-17). Additionally he reports personal fees and other from Cell Signaling Technology and Sanofi USA, grants and personal fees from Pfizer, personal fees from Novo Nordisk, other from Volastra, EIP Pharma, and Faeth, outside the submitted work. In addition, Dr. Cantley has a patent US8883438 licensed to Agios Pharmaceuticals, a patent US8715665 licensed to BIDMC, a patent US5532167 licensed to BIDMC, a patent US8552050 licensed to BIDMC, a patent US6004757 licensed to BIDMC, a patent US9493813 licensed to BIDMC, a patent US9745631 licensed to BIDMC, a patent US9119858 licensed to GENESYS RESEARCH INSTITUTE, a patent US10138479 licensed to BIDMC, a patent US6462173 licensed to CLEAR-COAT HOLDING, a patent US8877791 licensed to BIDMC, a patent US20190010144A1 licensed to Cornell University, California Institute of Biological Research, a patent US20170073760A1 pending to BIDMC, and a patent US20190136238A1 pending to BIDMC.CA reports personal fees from Tesaro, Immunogen, Eisai/Merck, and Mateon Therapeutics, grants and personal fees from Clovis, and grants from Genentech, AbbVie, and Astra Zeneca, outside the submitted work. Funding Information: RLC reports grants from the NIH, Gateway Foundation, and V-Foundation during the conduct of this study. He reports grants and personal fees from AstraZeneca, Clovis, Genmab, Roche/Genentech, and Janssen outside of the submitted work. He reports grants from Merck outside the submitted work. He reports personal fees from Tesaro, Medivation, Gamamab, Agenus, Regeneron, and OncoQuest outside the submitted work. Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2020",

month = may,

doi = "10.1016/j.gore.2020.100546",

language = "English (US)",

volume = "32",

journal = "Gynecologic Oncology Reports",

issn = "2211-338X",

publisher = "Elsevier BV",

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TY - JOUR

T1 - Results of an abbreviated phase II study of AKT inhibitor MK-2206 in the treatment of recurrent platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal carcinoma (NCT 01283035)

AU - Lee, Elizabeth K.

AU - Tan-Wasielewski, Zhenying

AU - Aghajanian, Carol

AU - Coleman, Robert L.

AU - Curtis, Jennifer

AU - Hirsch, Michelle S.

AU - Matulonis, Ursula A.

AU - Cantley, Lewis C.

AU - Mills, Gordon B.

AU - Doyle, L. Austin

AU - Liu, Joyce F.

N1 - Funding Information: GBM is an advisory board member with AstraZeneca, ImmunoMET, Ionis, Nuevolution, PDX bio, Signalchem, Symphogen, and Tarveda, has stock options with Catena Pharmaceuticals, ImmunoMet, SignalChem, Spindle Top Ventures and Tarveda, travel support from Chrysallis Bio, and has licensed technology to Nanostring and Myriad Genetics. GBM is supported by a kind gift from the Miriam and Sheldon Adelson Medical Research Foundation , the Ovarian Cancer Research Foundation , The Breast Cancer Research Foundation , Prospect Creek Foundation , The Komen Foundation SAC110052 , and NCI grants: CA217685 , CA217842 , and CA098258 . Funding Information: LCC owns equity in, receives compensation from, and serves on the scientific advisory board of Agios Pharmaceuticals. He is also a founder of and receives laboratory support from Petra Pharmaceuticals and receives compensation for being on the scientific advisory board of Petra Pharmaceuticals. No drugs from these companies were involved in this study. LCC reports support through the National Cancer Institute of the National Institutes of Health under Award Number R35CA197588 , and through a Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (Grant number: SU2C-AACR-DT22-17 ). Additionally he reports personal fees and other from Cell Signaling Technology and Sanofi USA, grants and personal fees from Pfizer, personal fees from Novo Nordisk, other from Volastra, EIP Pharma, and Faeth, outside the submitted work. In addition, Dr. Cantley has a patent US8883438 licensed to Agios Pharmaceuticals, a patent US8715665 licensed to BIDMC, a patent US5532167 licensed to BIDMC, a patent US8552050 licensed to BIDMC, a patent US6004757 licensed to BIDMC, a patent US9493813 licensed to BIDMC, a patent US9745631 licensed to BIDMC, a patent US9119858 licensed to GENESYS RESEARCH INSTITUTE, a patent US10138479 licensed to BIDMC, a patent US6462173 licensed to CLEAR-COAT HOLDING, a patent US8877791 licensed to BIDMC, a patent US20190010144A1 licensed to Cornell University, California Institute of Biological Research, a patent US20170073760A1 pending to BIDMC, and a patent US20190136238A1 pending to BIDMC. Funding Information: CA reports personal fees from Tesaro, Immunogen, Eisai / Merck , and Mateon Therapeutics, grants and personal fees from Clovis, and grants from Genentech , AbbVie , and Astra Zeneca, outside the submitted work. Funding Information: This work was funded by a Stand Up to Cancer Dream Team Translational Research Grant, a Program of the Entertainment Industry Foundation ( SU2C-AACR-DT0209 ). Research grants are administered by the American Association for Cancer Research , the scientific partner of SU2C. The study was sponsored by the National Cancer Institute under the Cancer Therapy Evaluation Program. Funding Information: This work was funded by a Stand Up to Cancer Dream Team Translational Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-DT0209). Research grants are administered by the American Association for Cancer Research, the scientific partner of SU2C. The study was sponsored by the National Cancer Institute under the Cancer Therapy Evaluation Program.GBM is an advisory board member with AstraZeneca, ImmunoMET, Ionis, Nuevolution, PDX bio, Signalchem, Symphogen, and Tarveda, has stock options with Catena Pharmaceuticals, ImmunoMet, SignalChem, Spindle Top Ventures and Tarveda, travel support from Chrysallis Bio, and has licensed technology to Nanostring and Myriad Genetics. GBM is supported by a kind gift from the Miriam and Sheldon Adelson Medical Research Foundation, the Ovarian Cancer Research Foundation, The Breast Cancer Research Foundation, Prospect Creek Foundation, The Komen Foundation SAC110052, and NCI grants: CA217685, CA217842, and CA098258.LCC owns equity in, receives compensation from, and serves on the scientific advisory board of Agios Pharmaceuticals. He is also a founder of and receives laboratory support from Petra Pharmaceuticals and receives compensation for being on the scientific advisory board of Petra Pharmaceuticals. No drugs from these companies were involved in this study. LCC reports support through the National Cancer Institute of the National Institutes of Health under Award Number R35CA197588, and through a Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (Grant number: SU2C-AACR-DT22-17). Additionally he reports personal fees and other from Cell Signaling Technology and Sanofi USA, grants and personal fees from Pfizer, personal fees from Novo Nordisk, other from Volastra, EIP Pharma, and Faeth, outside the submitted work. In addition, Dr. Cantley has a patent US8883438 licensed to Agios Pharmaceuticals, a patent US8715665 licensed to BIDMC, a patent US5532167 licensed to BIDMC, a patent US8552050 licensed to BIDMC, a patent US6004757 licensed to BIDMC, a patent US9493813 licensed to BIDMC, a patent US9745631 licensed to BIDMC, a patent US9119858 licensed to GENESYS RESEARCH INSTITUTE, a patent US10138479 licensed to BIDMC, a patent US6462173 licensed to CLEAR-COAT HOLDING, a patent US8877791 licensed to BIDMC, a patent US20190010144A1 licensed to Cornell University, California Institute of Biological Research, a patent US20170073760A1 pending to BIDMC, and a patent US20190136238A1 pending to BIDMC.CA reports personal fees from Tesaro, Immunogen, Eisai/Merck, and Mateon Therapeutics, grants and personal fees from Clovis, and grants from Genentech, AbbVie, and Astra Zeneca, outside the submitted work. Funding Information: RLC reports grants from the NIH, Gateway Foundation, and V-Foundation during the conduct of this study. He reports grants and personal fees from AstraZeneca, Clovis, Genmab, Roche/Genentech, and Janssen outside of the submitted work. He reports grants from Merck outside the submitted work. He reports personal fees from Tesaro, Medivation, Gamamab, Agenus, Regeneron, and OncoQuest outside the submitted work. Publisher Copyright: © 2020 The Authors

PY - 2020/5

Y1 - 2020/5

N2 - Platinum-resistant, recurrent, high grade epithelial ovarian carcinoma remains challenging to treat. Chemotherapy produces limited responses with modest survival benefits in the treatment of recurrent disease. In this context, targeted therapies may improve upon conventional therapies. PI3K/AKT pathway alterations are frequently found in several cancer types, including ovarian cancer, and thus AKT inhibition is a rational targeted therapy. Here we report the results of an abbreviated trial of AKT inhibitor MK-2206 in platinum resistant high grade serous ovarian, fallopian tube, and primary peritoneal cancer with PTEN loss.

AB - Platinum-resistant, recurrent, high grade epithelial ovarian carcinoma remains challenging to treat. Chemotherapy produces limited responses with modest survival benefits in the treatment of recurrent disease. In this context, targeted therapies may improve upon conventional therapies. PI3K/AKT pathway alterations are frequently found in several cancer types, including ovarian cancer, and thus AKT inhibition is a rational targeted therapy. Here we report the results of an abbreviated trial of AKT inhibitor MK-2206 in platinum resistant high grade serous ovarian, fallopian tube, and primary peritoneal cancer with PTEN loss.

KW - AKT inhibitor

KW - MK-2206

KW - PI3K/AKT pathway

KW - PTEN

KW - Platinum resistant ovarian cancer

KW - Serous ovarian carcinoma

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VL - 32

JO - Gynecologic Oncology Reports

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ER -

Results of an abbreviated phase II study of AKT inhibitor MK-2206 in the treatment of recurrent platinum-resistant high grade serous ovarian, fallopian tube, or primary peritoneal carcinoma (NCT 01283035)

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