1294P - Phase I study for ceritinib (LDK378) in Japanese patients with ALK genetic alterations

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Pathology/Molecular Biology
Presenter Haruyasu Murakami
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors H. Murakami1, T. Seto2, T. Takahashi3, A. Horiike4, F. Hirai5, N. Suenaga6, T. Tajima7, K. Tokushige8, A.L. Boral9, M. Robson10, M. Nishio11
  • 1Division Of Thoracic Oncology, Shizuoka Cancer Center, 411-8777 - Sunto-gun/JP
  • 2Department Of Thoracic Oncology, National Kyushu Cancer Center, 811-1395 - Fukuoka/JP
  • 3Thoracic Oncology, Shizuoka Cancer Center, JP-411-8777 - Shizuoka/JP
  • 4Thoracic Oncology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 135-8550 - Koto-ku, Tokyo/JP
  • 5Department Of Thoracic Oncology, National Kyushu Cancer Center, 811-1396 - Fukuoka/JP
  • 6Oncology Translational Medicine, Novartis Pharma, Tokyo/JP
  • 7Oncology Clinical Development, Novartis Pharma, Tokyo/JP
  • 8Oncology Biometrics And Data Management, Novartis Pharma, Tokyo/JP
  • 9Oncology Translational Medicine, Novartis Institutes for Biomedical Research, Inc, 02139 - Cambridge/US
  • 10Oncology Clincal Development, Novartis Pharma KK, Tokyo/JP
  • 11Thoracic Medical Oncology, Cancer Institute Hospital of JFCR, 135-8550 - Tokyo/JP



ALK rearranged (ALK+) NSCLC is sensitive to tyrosine kinase inhibitors (TKI) such as crizotinib and alectinib, but resistance develops. A global Phase I trial (Shaw et al, NEJM 2014) of ceritinib, a novel ALK TKI, established 750 mg daily as MTD, with an ORR of 59%. The primary objective of the present study was to estimate MTD in Japanese pts.


The study enrolled Japanese pts with ALK+ advanced tumors. Adaptive dose escalations were guided by a Bayesian model.


19 pts (18 NSCLC) received ceritinib 300-750 mg QD. The most common AEs were gastrointestinal toxicities (nausea 95%, diarrhea, vomiting 74%). Two DLTs occurred; Grade 3 lipase increase at 600 mg and Grade 3 drug-induced liver injury at 750 mg. ORR was 58% (11/19). In 9 crizotinib- and 3 alectinib-pretreated pts, partial responses were achieved by 5 and 2 pts. One alectinib/crizotinib-pretreated pt with disease progression in the brain had a 43% reduction in target tumor lesions.


Ceritinib MTD was 750 mg QD in Japanese pts, with a safety profile comparable to that in the global trial. Antitumor activity was observed in ALK TKI-resistant pts. The dose expansion part to further examine the activity of ceretinib in alectinib resistant pts is ongoing, and preliminary results of this part will be presented.


T. Seto: I have received research funding and honoraria from Novartis Pharma K.K; N. Suenaga: Naoko Suenaga is an employee of Novartis Pharma K.K; T. Tajima: Takeshi Tajima is an employee of Novartis Pharma K.K; K. Tokushige: Kota Tokushige is an employee of Novartis Pharma K.K; A.L. Boral: Anthony Boral is a full time employee of Novartis Pharmaceuticals; M. Robson: Matthew Robson is an employee of Novartis Pharma K.K. All other authors have declared no conflicts of interest.