Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 1

4407 - Phase 0 Trial of Ceritinib in Brain Metastases and Recurrent Glioblastoma


28 Sep 2019


Poster Display session 1


Tumour Site

Central Nervous System Malignancies


Shwetal Mehta


Annals of Oncology (2019) 30 (suppl_5): v143-v158. 10.1093/annonc/mdz243


S. Mehta1, R. Fiorelli1, J. Li2, X. Bao2, A. DeRogatis1, C. Pennington-Krygier1, S. Kim3, N. Sanai1

Author affiliations

  • 1 Ivy Brain Tumor Center, Barrow Neurological Institute, 85013 - Phoenix/US
  • 2 Pharmacology Core, Karmanos Cancer Institute, 48201 - Detroit/US
  • 3 Cancer Biology, Karmanos Cancer Institute, 48201 - Detroit/US


Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 4407


Ceritinib is an orally bioavailable, small molecule inhibitor for ALK/IGFR1/FAK, which are highly expressed in glioblastoma and brain metastases. Preclinical and clinical data suggest that ceritinib has activity in central nervous system (CNS) malignancies, but to date there is no direct evidence in patients. This study assessed the pharmacokinetics (PK) and pharmacodynamics (PD) of ceritinib in recurrent glioblastoma and brain metastasis patients.


Three brain metastasis and 7 glioblastoma patients with high expression of pSTAT5b/pFAK/pIGFR1 were enrolled and treated with oral ceritinib daily (750 mg) for 10 days prior to tumor resection. Plasma, tumor, and cerebrospinal fluid (CSF) samples were collected at ∼ 4 and 24 h following the last dose. Total and unbound drug concentrations were determined using LC-MS/MS. PD response was assessed by immunohistochemical analysis of pALK, pFAK, pIGFR1, and pIRS1 staining in treated tumor and matched archival tissues.


Ceritinib was highly bound to human plasma protein (median fraction unbound (Fu), 1.4%) and to brain tumor tissue (median Fu, 0.073% and 0.14% in enhancing and non-enhancing regions respectively). There was a large interindividual variability in drug CNS penetration, with the median unbound concentrations in enhancing, non-enhancing, and CSF of 0.040, 0.006, and 0.012 µM, respectively. The median unbound tumor-to-plasma ratio was 2.44 and 0.33 in enhancing and non-enhancing areas, respectively. In one patient with brain metastasis, drug binding to enhancing tumor was significantly lower (Fu, 1.62%), resulting in a higher unbound drug tumor concentration and CSF concentration as compared to those in glioblastoma patients. In all patients, no changes in PD markers were detected.


Ceritinib is highly bound to plasma proteins and tumor tissues. Unbound drug concentrations achieved in brain metastasis and glioblastoma are unlikely sufficient for target modulation.

Clinical trial identification


Editorial acknowledgement

Legal entity responsible for the study

The authors.


The Ben and Catherine Ivy Foundation.


All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.