A first-time-in-human study of GSK2636771, a phosphoinositide 3 kinase beta-selective inhibitor, in patients with advanced solid tumors

Clinical Cancer Research

Volumn 23, Issue 19, 2017, Pages 5981-5992

  Mateo, Joaquin ^a   Ganji, Gopinath ^b   Lemech, Charlotte ^c   Burris, Howard A ^d   Han, Sae Won ^e   Swales, Karen ^a   Decordova, Shaun ^a   DeYoung, M Phillip ^b   Smith, Deborah A ^f   Kalyana Sundaram, Shanker ^b   Wu, Jiuhua ^g   Motwani, Monica ^h   Kumar, Rakesh ⁱ   Tolson, Jerry M ^b   Rha, Sun Young ^j   Chung, Hyun Cheol ^j   Eder, Joseph P ^k   Sharma, Sunil ^l   Bang, Yung Jue ^e   Infante, Jeffrey R ^d   Yan, Li ^b   De Bono, Johann S ^a   Arkenau, Hendrik Tobias ^c   more..

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b GLAXOSMITHKLINE   (United States)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

^d SARAH CANNON RESEARCH INSTITUTE   (United States)

^e Seoul National University Hospital   (South Korea)

^f PAREXEL INTERNATIONAL   (United States)

^g Biostat Consulting Inc   (United States)

^h ABBVIE INC   (United States)

ⁱ Yonsei University College of Medicine ^*  (United States)

^j Yonsei University College of Medicine   (South Korea)

^k YALE CANCER CENTER   (United States)

^l UNIVERSITY OF UTAH   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; GSK 2636771; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; UNCLASSIFIED DRUG; PROTEIN KINASE INHIBITOR;

ADULT; AGED; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BREAST CANCER; CASTRATION RESISTANT PROSTATE CANCER; CENTRAL NERVOUS SYSTEM CANCER; COLORECTAL CANCER; DECREASED APPETITE; DEHYDRATION; DIARRHEA; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; DYSGEUSIA; ENDOMETRIUM CANCER; FATIGUE; FEMALE; GENE; GENE AMPLIFICATION; HEAD AND NECK CANCER; HEADACHE; HUMAN; HUMAN CELL; HYPERTENSION; HYPOALBUMINEMIA; HYPOCALCEMIA; HYPOPHOSPHATEMIA; INTESTINE OBSTRUCTION; KIDNEY DISEASE; MACULOPAPULAR RASH; MAJOR CLINICAL STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; MELANOMA; MOUSE; NAUSEA; NON SMALL CELL LUNG CANCER; NONHUMAN; OVARY CANCER; PHARMACODYNAMICS; PHASE 2 CLINICAL TRIAL; PIK3CB GENE; PRIORITY JOURNAL; PROTEINURIA; PRURITUS; RASH; SIDE EFFECT; SOLID MALIGNANT NEOPLASM; STOMACH CANCER; TREATMENT RESPONSE; UPPER RESPIRATORY TRACT INFECTION; URINE RETENTION; UTERINE CERVIX CANCER; VOMITING; ADVERSE DRUG REACTION; ANTAGONISTS AND INHIBITORS; CANCER STAGING; CLINICAL TRIAL; DRUG ADMINISTRATION; GENETICS; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEOPLASM; PATHOLOGY; PHASE 1 CLINICAL TRIAL;

ADULT; AGED; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; FEMALE; HUMANS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEOPLASM STAGING; NEOPLASMS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN KINASE INHIBITORS;

EID: 85032305458     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-17-0725     Document Type: Article

References (40)

1. Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 2009;8:627–44.
2. Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMi-chael JF, et al. Comprehensive molecular portraits of human breast tumours. Nature 2012;490:61–70.
3. Muzny DM, Bainbridge MN, Chang K, Dinh HH, Drummond JA, Fowler G, et al. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012;487:330–7.
4. Di Cristofano A, Pandolfi PP. The multiple roles of PTEN in tumor suppression. Cell 2000;100:387–90.
5. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 2004;304:554.
6. Courtney KD, Corcoran RB, Engelman JA. The PI3K pathway as drug target in human cancer. J Clin Oncol 2010;28:1075–83.
7. Rodon J, Dienstmann R, Serra V, Tabernero J. Development of PI3K inhibitors: lessons learned from early clinical trials. Nat Rev Clin Oncol 2013;10:143–53.
8. Chandarlapaty S, Sawai A, Scaltriti M, Rodrik-Outmezguine V, Grbovic-Huezo O, Serra V, et al. AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Cancer Cell 2011; 19:58–71.
9. Stratikopoulos EE, Dendy M, Szabolcs M, Khaykin AJ, Lefebvre C, Zhou MM, et al. Kinase and BET inhibitors together clamp inhibition of PI3K signalingandovercomeresistancetotherapy.CancerCell2015;27:837–51.
10. Ihle NT, Lemos R Jr, Wipf P, Yacoub A, Mitchell C, Siwak D, et al. Mutations in the phosphatidylinositol-3-kinase pathway predict for antitumor activity of the inhibitor PX-866 whereas oncogenic Ras is a dominant predictor for resistance. Cancer Res 2009;69:143–50.
11. Busaidy NL, Farooki A, Dowlati A, Perentesis JP, Dancey JE, Doyle LA, et al. Management of metabolic effects associated with anticancer agents targeting the PI3K-Akt-mTOR pathway. J Clin Oncol 2012;30: 2919–28.
12. Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 2006;7:606–19.
13. Brachmann SM, Kleylein-Sohn J, Gaulis S, Kauffmann A, Blommers MJ, Kazic-Legueux M, et al. Characterization of the mechanism of action of the pan class I PI3K inhibitor NVP-BKM120 across a broad range of concentrations. Mol Cancer Ther 2012;11:1747–57.
14. Jia S, Liu Z, Zhang S, Liu P, Zhang L, Lee SH, et al. Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis. Nature 2008; 454:776–9.
15. Ni J, Liu Q, Xie S, Carlson C, Von T, Vogel K, et al. Functional characterization of an isoform-selective inhibitor of PI3K-p110beta as a potential anticancer agent. Cancer Discov 2012;2:425–33.
16. Schwartz S, Wongvipat J, Trigwell CB, Hancox U, Carver BS, Rodrik-Outmezguine V, et al. Feedback suppression of PI3Kalpha signaling in PTEN-mutated tumors is relieved by selective inhibition of PI3Kbeta. Cancer Cell 2015;27:109–22.
17. Wee S, Wiederschain D, Maira SM, Loo A, Miller C, deBeaumont R, et al. PTEN-deficient cancers depend on PIK3CB. Proc Natl Acad Sci U S A 2008;105:13057–62.
18. Foukas LC, Claret M, Pearce W, Okkenhaug K, Meek S, Peskett E, et al. Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulation. Nature 2006;441:366–70.
19. Carver BS, Chapinski C, Wongvipat J, Hieronymus H, Chen Y, Chandarlapaty S, et al. Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell 2011;19:575–86.
20. Ferraldeschi R, Nava Rodrigues D, Riisnaes R, Miranda S, Figueiredo I, Rescigno P, et al. PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate. Eur Urol 2015;67: 795–802.
21. Reid AH, Attard G, Danila DC, Oommen NB, Olmos D, Fong PC, et al. Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate. J Clin Oncol 2010;28:1489–95.
22. Bosch A, Li Z, Bergamaschi A, Ellis H, Toska E, Prat A, et al. PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor-positive breast cancer. Sci Transl Med 2015; 7:283ra51.
23. Crowder RJ, Phommaly C, Tao Y, Hoog J, Luo J, Perou CM, et al. PIK3CA and PIK3CB inhibition produce synthetic lethality when combined with estrogen deprivation in estrogen receptor-positive breast cancer. Cancer Res 2009;69:3955–62.
24. Serra V, Scaltriti M, Prudkin L, Eichhorn PJ, Ibrahim YH, Chandarlapaty S, et al. PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer. Oncogene 2011;30: 2547–57.
25. Zhang Y, Moerkens M, Ramaiahgari S, de Bont H, Price L, Meerman J, et al. Elevated insulin-like growth factor 1 receptor signaling induces antiestro-gen resistance through the MAPK/ERK and PI3K/Akt signaling routes. Breast Cancer Res 2011;13:R52.
26. Bantscheff M, Eberhard D, Abraham Y, Bastuck S, Boesche M, Hobson S, et al. Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors. Nat Biotechnol 2007;25: 1035–44.
27. Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 2008; 26:1148–59.
28. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228–47.
29. Dienstmann R, Rodon J, Serra V, Tabernero J. Picking the point of inhibition: a comparative review of PI3K/AKT/mTOR pathway inhibitors. Mol Cancer Ther 2014;13:1021–31.
30. Nakanishi Y, Walter K, Spoerke JM, O'Brien C, Huw LY, Hampton GM, et al. Activating mutations in PIK3CB confer resistance to PI3K inhibition and define a novel oncogenic role for p110beta. Cancer Res 2016; 76:1193–203.
31. Pazarentzos E, Giannikopoulos P, Hrustanovic G, St John J, Olivas VR, Gubens MA, et al. Oncogenic activation of the PI3-kinase p110beta isoform via the tumor-derived PIK3Cbeta(D1067V) kinase domain mutation. Oncogene 2016;35:1198–205.
32. Garcia A, Kim S, Bhavaraju K, Schoenwaelder SM, Kunapuli SP. Role of phosphoinositide 3-kinase beta in platelet aggregation and thromboxane A2 generation mediated by Gi signalling pathways. Biochem J 2010;429: 369–77.
33. Hammerman PS, Lawrence MS, Voet D, Jing R, Cibulskis K, Sivachenko A, et al. Comprehensive genomic characterization of squamous cell lung cancers. Nature 2012;489:519–25.
34. Lawrence MS, Sougnez C, Lichtenstein L, Cibulskis K, Lander E, Gabriel SB, et al. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015;517:576–82.
35. Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, et al. Integrative clinical genomics of advanced prostate cancer. Cell 2015;161:1215–28.
36. Bell D, Berchuck A, Birrer M, Chien J, Cramer DW, Dao F, et al. Integrated genomic analyses of ovarian carcinoma. Nature 2011;474:609–15.
37. Ciriello G, Gatza ML, Beck AH, Wilkerson MD, Rhie SK, Pastore A, et al. Comprehensive molecular portraits of invasive lobular breast cancer. Cell 2015;163:506–19.
38. Janku F, Wheler JJ, Naing A, Falchook GS, Hong DS, Stepanek VM, et al. PIK3CA mutation H1047R is associated with response to PI3K/AKT/mTOR signaling pathway inhibitors in early-phase clinical trials. Cancer Res 2013;73:276–84.
39. Dbouk HA, Khalil BD, Wu H, Shymanets A, Nurnberg B, Backer JM. Characterization of a tumor-associated activating mutation of the p110beta PI 3-kinase. PLoS One 2013;8:e63833.
40. Cancer Genome Atlas Research N. The molecular taxonomy of primary prostate cancer. Cell 2015;163:1011–25.