A first-in-human phase I/II study of ALK inhibitor CH5424802 in patients with ALK-positive NSCLC.

Lung Cancer - Non-Small Cell Metastatic
Session Type and Session Title: 
General Poster Session, Lung Cancer - Non-small Cell Metastatic
Abstract Number: 


J Clin Oncol 30, 2012 (suppl; abstr 7602)
Katsuyuki Kiura, Takashi Seto, Nobuyuki Yamamoto, Makoto Nishio, Kazuhiko Nakagawa, Tomohide Tamura; Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan; National Kyushu Cancer Center, Fukuoka, Japan; Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan; Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan; Kinki University School of Medicine, Osaka, Japan; National Cancer Center Hospital, Tokyo, Japan

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Abstract Disclosures


Background: Anaplastic lymphoma kinase (ALK) is a tyrosine kinase constitutively activated in a subset of non-small cell lung cancer (NSCLC) following chromosomal gene translocation. CH5424802 was identified as a potent, selective, and oral ALK inhibitor with a unique chemical scaffold, showing preferential antitumor activity against NSCLC cells expressing EML4-ALK fusion in vitro and in vivo (Cancer Cell, 2011). Our results support the potential of CH5424802 as a new therapeutic opportunity for patients (pts) with ALK-positive NSCLC. Methods: Pts with ALK-positive NSCLC received CH5424802 twice daily orally until progressive disease or toxicity was observed. In the phase I portion, dose was escalated using an accelerated titration scheme. The primary objectives were to investigate the safety, tolerability and pharmacokinetic (PK) parameters under fasting conditions, and to determine the recommended dose (RD) for use in the phase II portion. The primary objectives of the phase II portion were to investigate the efficacy and safety at the RD. The phase I portion was amended to include an investigation under non-fasting conditions in addition to fasting conditions. Results: 15 pts (M/F: 9/6) were treated with CH5424802 under fasting conditions in 6 cohorts (20 mg bid to 300 mg bid) and 9 pts (M/F: 2/7) were treated under non-fasting conditions in 2 cohorts (240 mg bid and 300 mg bid). Median age was 42.5 years. The highest dose level defined in the protocol (300 mg bid) did not reach the MTD. Thus, a DLT was not determined. Toxicities were mild to moderate. The most frequent toxicity was grade 1 myalgia. Grade 3 toxicity (cases) occurred as follows; hypophosphatemia (2), neutropenia (2), blood CPK increased (1) and hypermagnesemia (1). PK data from the fasting cohorts showed dose-dependent increases of Cmax and AUC. All pts at all dose levels achieved tumor regression. At dose levels 240 mg bid or more under fasting conditions, all 7 pts with measurable lesions achieved a partial response. So far, 11 pts have been on study treatment ≥ 6 months. Conclusions: CH5424802 was well tolerated with promising efficacy in pts with ALK-positive NSCLC. The phase II portion is ongoing.