441O - A phase I/II study of ALK inhibitor CH5424802 in patients with ALK-positive NSCLC; safety and efficacy interim results of the phase II portion

Date 29 September 2012
Event ESMO Congress 2012
Session Developmental therapeutics
Topics Drug Development
Non-Small-Cell Lung Cancer, Metastatic
Presenter Makoto Nishio
Authors M. Nishio1, K. Kiura2, K. Nakagawa3, T. Seto4, A. Inoue5, M. Maemondo6, T. Hida7, M. Harada8, H. Yoshioka9, T. Tamura10
  • 1Thracic Oncology Center, Cancer Institute Hospital of JFCR, 135-8550 - Tokyo/JP
  • 2Department Of Respiratory Medicine, Okayama University Hospital, 7008558 - Okayama/JP
  • 3Medical Oncology, Kinki University School of Medicine, JP-589-8511 - Osaka/JP
  • 4Thoracic Oncology, National Kyushu Cancer Center, 811-1395 - Fukuoka/JP
  • 5Department Of Respiratory Medicine, Tohoku University, JP-980-8575 - Sendai/JP
  • 6Department Of Respiratory Medicine, Miyagi Cancer Center, 981-1293 - Natori/JP
  • 7Thoracic Oncology, Aichi Cancer Center, 464-8681 - Nagoya/JP
  • 8Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, Sapporo/JP
  • 9Respiratory, Kurashiki Central Hospital, Kurashiki/JP
  • 10Division Of Internal Medicine And Thoracic Oncology, National Cancer Center Hospital, Tokyo/JP

Abstract

Background

Anaplastic lymphoma kinase (ALK) is a tyrosine kinase constitutively activated following chromosomal gene translocation in a subset of non-small cell lung cancer (NSCLC). CH5424802, an oral ALK inhibitor, was well tolerated with promising efficacy in patients (pts) with ALK-positive NSCLC in the phase I portion (ASCO 2012). Here we report the interim results of the ongoing phase II portion.

Methods

The primary objective of the phase II portion was to investigate the efficacy and safety at the recommended dose (RD) determined in the phase I portion. Pts with ALK-positive NSCLC, measurable disease, and no prior ALK inhibitor therapy were treated with CH5424802 at 300 mg bid until progressive disease or intolerable toxicity.

Results

As of March 23, 2012, 34 pts have been enrolled: median age; 46 years, M/F; 16/18, ECOG PS 0/1; 17/17, never-smoker; 62%, number of prior chemotherapy 1/2/3/ > 4; 18/6/0/10. Among the first 15 pts, the response rate was 73.3% with 1 CR and 10 PRs. Main treatment-related adverse events (AEs) among the 34 pts were AST increased (7 pts), ALT increased (6), neutropenia (5), rash (4), nausea (4), myalgia (3), dysgeusia (3), constipation (3), blood CPK increased (3), blood bilirubin increased (3), and blood ALP increased (3), which were mostly Grade 1 except for neutropenia. Grade 3 treatment-related AEs were two cases of neutropenia. For treatment-related eye disorders which are frequent in crizotinib, only one Grade 1 case (vision blurred) was observed. No treatment-related AEs led to dose reduction. At the time of submission, 30 pts are on study (range 1 - 8 months).

Conclusion

CH5424802 demonstrated clinically meaningful antitumor activity with well tolerated toxicity profile. A phase I/II study in ALK-positive NSCLC pts previously treated with or without crizotinib is ongoing in the US.

Disclosure

M. Nishio: Corporate-sponsored research:Chugai pharmaceutical Co., Ltd., Pfizer.

K. Kiura: Corporate-sponsored research:Chugai pharmaceutical Co., Ltd., Pfizer.

K. Nakagawa: Corporate-sponsored research:Chugai pharmaceutical Co., Ltd., Pfizer.

T. Seto: Corporate-sponsored research:Chugai pharmaceutical Co., Ltd., Pfizer.

A. Inoue: Corporate-sponsored research:Chugai pharmaceutical Co., Ltd., Pfizer.

M. Maemondo: Corporate-sponsored research:Chugai pharmaceutical Co., Ltd.

T. Hida: Corporate-sponsored research:Chugai pharmaceutical Co., Ltd., Pfizer.

M. Harada: Corporate-sponsored research:Chugai pharmaceutical Co., Ltd., Pfizer.

H. Yoshioka: Corporate-sponsored research:Chugai pharmaceutical Co., Ltd.

T. Tamura: Corporate-sponsored research:Chugai pharmaceutical Co., Ltd.