Abstract
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.
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