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

Abstract

Aim

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.

Methods

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

Results

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.

Conclusions

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.

Disclosure

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.