138TiP - Ceritinib in patients (pts) with anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) metastatic to the brain and/o...

Date 17 April 2015
Event ELCC 2015
Session Poster lunch
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Laura Chow
Citation Annals of Oncology (2015) 26 (suppl_1): 29-44. 10.1093/annonc/mdv050
Authors L.Q. Chow1, F. Barlesi2, E.M. Bertino3, D. Kim4, M.J. van den Bent5, H. Wakelee6, P.Y. Wen7, P. Cazorla Arratia8, J. Shen8, F. Branle9
  • 1Department Of Medicine, University of Washington Seattle Cancer Care Alliance, 98109 - Seattle/US
  • 2Multidisciplinary Oncology & Therapeutic Innovation, Aix Marseille University, 13915 - Marseille/FR
  • 3Internal Medicine – Medical Oncology, The Ohio State University Wexner Medical Center, 43210 - Columbus/US
  • 4Internal Medicine, Seoul National University Hospital, 110-744 - Seoul/KR
  • 5Neurology, Erasmus MC Cancer Institute, 3075 EA - Rotterdam/NL
  • 6School Of Medicine, Stanford University, 94305 - Stanford/US
  • 7Neuro-oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 8Oncology, Novartis Pharmaceuticals Corporation, NJ 07936 - East Hanover/US
  • 9Oncology Global Development, Novartis Pharma AG, CH-4002 - Basel/CH



Although the ALK inhibitor (ALKi) crizotinib (CRZ) achieves high responses in pts with ALK+ NSCLC, disease progression within 1 year often occurs, with the brain/central nervous system (CNS) as a common site of progression and relapse. Ceritinib is a novel oral ALKi with 20-fold greater potency than CRZ in enzymatic assays that crosses the blood-brain barrier with good CNS penetration in preclinical studies. In the pivotal phase I study (NCT01283516), ceritinib was highly active in ALK+ NSCLC pts (regardless of prior CRZ exposure) and achieved intracranial responses in 7 of 14 pts with measurable baseline brain lesions. The adverse events profile in these pts was similar to that of the full study population.

Trial design

This international prospective phase II open-label study is designed to evaluate the antitumor activity of ceritinib in pts with ALK+ NSCLC metastatic to the brain or leptomeninges (ASCEND-7; CLDK378A2205). Eligible pts must have centrally assessed ALK+ NSCLC metastatic to the brain and ≥1 extracranial measurable lesion using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Pts must be neurologically stable ≥1 week prior to study drug and will be allocated to 1 of 5 cohorts depending on prior treatment:

ARMS 1-4 (pts w/active* brain mets, w/o LC) Prior ALKi treatment NO prior ALKi treatment
Prior whole brain radiotherapy (WBRT) ARM 1 ARM 3
NO prior WBRT ARM 2 ARM 4
ARM 5: pts with leptomeningeal carcinomatosis (LC) with or without evidence of active lesion at baseline

*Lesion free of local treatment (stereotactic or WBRT) or lesions in unequivocal progression after radiotherapy. Oral ceritinib 750 mg/day will be dosed on a continuous schedule and study assessments are consistent across cohorts. The primary and key secondary objectives are to evaluate whole body overall response rate and disease control rate, respectively. Other secondary objectives include assessment of intracranial and extracranial responses for all pts and for each cohort 1–4; overall survival and safety for all pts and for each cohort 1–5; and ceritinib pharmacokinetics in all pts. Enrolment is ongoing.

Clinical trial identification NCT02336451


L.Q. Chow: Consultant: Novartis. Funding Other: Research support (funds directly to University of Washington).

F. Barlesi: Consultant: AstraZeneca, Boehringer-Ingelheim, Daichii Saiko, Eli Lilley Oncology, F. Hoffmann-La Roche Ltd, Glaxo-Smithkline, Novartis, Pfizer, Pierre Fabre.

E.M. Bertino: Advisory board: Boehringer-Ingelheim (afatinib). Steering committee: Novartis (ceritinib).

D.-W. Kim: Consultant: Novartis, Pfizer.

M.J. van den Bent: Consultant: Novartis. Advisory board: Novartis.

H. Wakelee: Grant for trial conduct: AstraZeneca. Current consultancy: Peregrine. Ongoing grants: Novartis, BMS, Clovis, Xcovery, Celegene, Roche/Genentech, Medimmune, Pfizer.

P.Y. Wen: Research: AbbVie, Agios, Angiochem, AZ, Cubist, Exelixis, Genetech/Roche, GSK, Karyopharm, Merck, Novartis, Sanofi-Aventis, Vascular Biogenics. Ad board: AbbVie, Celldex, Genetech/Roche, Novartis, Novocure, SigmaTau, Midatech, Momenta, Vascular Biogenics. Speaker: Merck.

P. Cazorla Arratia and J. Shen: Employee of Novartis Pharmaceuticals Corporation.

F. Branle: Employee of Novartis