A phase I, pharmacokinetic and pharmacodynamic study of GSK2256098, a focal adhesion kinase inhibitor, in patients with advanced solid tumors

Annals of Oncology

Volumn 27, Issue 12, 2016, Pages 2268-2274

  Soria, J C ^a   Gan, H K ^b,c   Blagden, S P ^d   Plummer, R ^e   Arkenau, H T ^f   Ranson, M ^g   Evans, T R J ^h   Zalcman, G ⁱ   Bahleda, R ^a   Hollebecque, A ^a   Lemech, C ^f   Dean, E ^g   Brown, J ^h   Gibson, D ^j   Peddareddigari, V ^j   Murray, S ^j   Nebot, N ^j   Mazumdar, J ^j   Swartz, L ^j   Auger, K R ^j   Fleming, R A ^j   Singh, R ^j   Millward, M ^k   more..

^a INSTITUT GUSTAVE ROUSSY   (France)

^b OLIVIA NEWTON JOHN CANCER RESEARCH INSTITUTE   (Australia)

^c LA TROBE UNIVERSITY   (Australia)

^d HAMMERSMITH HOSPITAL   (United Kingdom)

^e Northern Centre for Cancer Care   (United Kingdom)

^f SARAH CANNON RESEARCH INSTITUTE   (United Kingdom)

^g UNIVERSITY OF MANCHESTER   (United Kingdom)

^h UNIVERSITY OF GLASGOW   (United Kingdom)

ⁱ CAEN UNIVERSITY HOSPITAL   (France)

^j NC and Upper Providence   (United States)

^k UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

more..

Author keywords

focal adhesion kinase; merlin; mesothelioma; NF2; pharmacodynamics; phase I

Indexed keywords

AMINOPYRIDINE DERIVATIVE; FOCAL ADHESION KINASE; GSK2256098; HYDROXAMIC ACID; MERLIN; PROTEIN KINASE INHIBITOR;

ADULT; ADVERSE DRUG REACTION; AGED; ANTAGONISTS AND INHIBITORS; BIOPSY; BLOOD; CLASSIFICATION; CLINICAL TRIAL; DISEASE FREE SURVIVAL; DOSE RESPONSE; FEMALE; GENETICS; HUMAN; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEOPLASM; PATHOLOGY; PHASE 1 CLINICAL TRIAL; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; AMINOPYRIDINES; BIOPSY; DISEASE-FREE SURVIVAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; FEMALE; FOCAL ADHESION PROTEIN-TYROSINE KINASES; HUMANS; HYDROXAMIC ACIDS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEOPLASMS; NEUROFIBROMIN 2; PROTEIN KINASE INHIBITORS;

EID: 85016954705     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mdw427     Document Type: Article

References (26)

1. Sulzmaier, F.J., Jean, C., Schlaepfer, D.D., FAK in cancer: mechanistic findings and clinical applications. Nature Rev Cancer 14 (2014), 598–610.
2. 925. Biochem Biophys Res Comm, 1696, 2014, 1701.
3. Zhao, J., Guan, J.L., Signal transduction by focal adhesion kinase in cancer. Cancer Metastasis Rev 28 (2009), 35–49.
4. McLean, G.W., Carragher, N.O., Avizienyte, E., et al. The role of focal adhesion kinase in cancer: a new therapeutic opportunity. Nat Rev Cancer 5 (2005), 505–515.
5. Ozkal, S., Peterson, J.C., Tedoldi, S., et al. Focal adhesion kinase (FAK) expression in normal and neoplastic lymphoid tissues. Path Res Prac 205 (2009), 781–788.
6. Recher, C., Ysebaert, L., Beyne-Rauzy, O., et al. Expression of focal adhesion kinase in acute myeloid leukemia is associated with enhanced blast migration, increased cellularity, and poor prognosis. Cancer Res 64 (2004), 3191–3197.
7. Ding, L., Sun, X., You, Y., Liu, N., Fu, Z., Expression of focal adhesion kinase and phosphorylated focal adhesion kinase in human gliomas is associated with unfavorable overall survival. Trans Res 156 (2010), 45–52.
8. Sood, A.K., Coffin, J.E., Schneider, G.B., et al. Biological significance of focal adhesion kinase in ovarian cancer: role in migration and invasion. Am J Path 165 (2004), 1087–1095.
9. Auger, K.R., Smitheman, K.N., Korenchuk, S., et al. The focal adhesion kinase inhibitor GSK2256098: a potent and selective inhibitor for the treatment of cancer. Eur J Cancer, 48, 2012, 118.
10. Chen, S., Johnson, N., Marszalek, J., et al. Pharmacological inhibition of focal adhesion kinase (FAK) in glioblastoma cell lines: implications for rational drug combination strategies. Cancer Res, 72(Suppl. 8), 2012 abstr 3714.
11. Bottsford-Miller, J., Sanguino, A., Thanapprapasr, D., et al. Enhancing anti-angiogenic therapy by blocking focal adhesion kinase. Cancer Res, 71(8 Suppl.), 2011 abstr LB-230.
12. Doughty, S.D., McLeod, K., Muir, M., et al. Anti-tumour activity of the focal adhesion kinase inhibitor GSK2256098C in ovarian cancer. Eur J Cancer, 48(Suppl 6), 2012, 173.
13. Simon, R., Freidlin, B., Rubinstein, L., et al. Accelerated titration designs for phase I clinical trials in oncology. J Natl Cancer Inst 89 (1997), 1138–1147.
14. Eisenhauer, E.A., Therasse, P., Bogaerts, J., et al. New response evaluation criteria in solid tumors: revised RECIST guideline (version 1.1). Eur J Cancer. 45 (2009), 228–247.
15. Byrne, M.J., Nowak, A.K., Modified RECIST criteria for assessment of response in malignant pleural mesothelioma. Ann Oncol 15 (2004), 257–260.
16. Fizazi, K., Morat, L., Chauveinc, L., et al. High detection rate of circulating tumor cells in blood of subjects with prostate cancer using telomerase activity. Ann Oncol. 18 (2007), 518–521.
17. Taylor, M., Rossler, J., Geoerger, B., et al. High levels of circulating VEGFR2+ bone marrow-derived progenitor cells correlate with metastatic disease in patients with pediatric solid malignancies. Clin Cancer Res 15 (2009), 4561–4571.
18. Jacques, N., Vinmond, N., Conforti, R., et al. Quantification of circulating mature endothelial cells using a whole blood four-color flow cytometric assay. J Immunol Method 337 (2008), 132–143.
19. Arkenau, H.T., Gazzah, A., Plummer, R., et al. A phase Ib dose-escalation study of GSK2256098 (FAKi) plus trametinib (MEKi) in patients with selected advanced solid tumors. J Clin Oncol, 33, 2015 (15 Suppl.): abstr 2593.
20. Sekido, Y., Molecular pathogenesis of malignant mesothelioma. Carcinogenesis 34 (2013), 1413–1419.
21. Poulikakos, P.I., Xiao, G.H., Gallagher, R., et al. Re-expression of the tumor suppressor NF2/merlin inhibits invasiveness in mesothelioma cells and negatively regulates FAK. Oncogene 25 (2006), 5960–5968.
22. Shapiro, I.M., Kolev, V.N., Vidal, C.M., et al. Merlin deficiency predicts FAK inhibitor sensitivity: a synthetic lethal relationship. Science Trans Med, 6, 2014, 237.
23. Krug, L.M., Kindler, H.L., Calvert, H., et al. Vorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Oncol 16 (2015), 447–456.
24. Brastianos, P.K., Horowitz, P.M., Santagata, S., et al. Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. Nat Genet 45 (2013), 285–289.
25. Jones, S.F., Siu, L.L., Bendell, J.C., et al. A phase I study of VS-6063, a second-generation focal adhesion kinase inhibitor, in patients with advanced solid tumors. Invest New Drugs 33 (2015), 1100–1107.
26. Zalcman, G., Mazières, J., Margery, J., et al. Bevacizumab 15 mg/kg plus cisplatin-pemetrexed (CP) triplet versus CP doublet in malignant pleural mesothelioma (MPM): results of the IFCT-GFPC-0701 MAPS randomized phase 3 trial. J Clin Oncol, 33, 2015 (15 Suppl.): abstr 7500.