TY - JOUR
T1 - CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study)
T2 - A single-arm, open-label, phase 1-2 study
AU - Seto, Takashi
AU - Kiura, Katsuyuki
AU - Nishio, Makoto
AU - Nakagawa, Kazuhiko
AU - Maemondo, Makoto
AU - Inoue, Akira
AU - Hida, Toyoaki
AU - Yamamoto, Nobuyuki
AU - Yoshioka, Hiroshige
AU - Harada, Masao
AU - Ohe, Yuichiro
AU - Nogami, Naoyuki
AU - Takeuchi, Kengo
AU - Shimada, Tadashi
AU - Tanaka, Tomohiro
AU - Tamura, Tomohide
N1 - Funding Information:
This study was designed and funded by the study sponsor (Chugai Pharmaceutical Co, Ltd) and monitored by a clinical research organisation (EPS Corporation). The clinical research organisation collected all data and the study sponsor did all data analysis and interpretation, with input from the authors and investigators. The initial draft of the report was reviewed and commented on by all authors, and by employees of Chugai Pharmaceutical Co, Ltd. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
PY - 2013/6
Y1 - 2013/6
N2 - Background: Currently, crizotinib is the only drug that has been approved for treatment of ALK-rearranged non-small-cell lung cancer (NSCLC). We aimed to study the activity and safety of CH5424802, a potent, selective, and orally available ALK inhibitor. Methods: In this multicentre, single-arm, open-label, phase 1-2 study of CH5424802, we recruited ALK inhibitor-naive patients with ALK-rearranged advanced NSCLC from 13 hospitals in Japan. In the phase 1 portion of the study, patients received CH5424802 orally twice daily by dose escalation. The primary endpoints of the phase 1 were dose limiting toxicity (DLT), maximum tolerated dose (MTD), and pharmacokinetic parameters. In the phase 2 portion of the study, patients received CH5424802 at the recommended dose identified in the phase 1 portion of the study orally twice a day. The primary endpoint of the phase 2 was the proportion of patients who had an objective response. Treatment was continued in 21-day cycles until disease progression, intolerable adverse events, or withdrawal of consent. The analysis was done by intent to treat. This study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-101264. Findings: Patients were enrolled between Sept 10, 2010, and April 18, 2012. The data cutoff date was July 31, 2012. In the phase 1 portion, 24 patients were treated at doses of 20-300 mg twice daily. No DLTs or adverse events of grade 4 were noted up to the highest dose; thus 300 mg twice daily was the recommended phase 2 dose. In the phase 2 portion of the study, 46 patients were treated with the recommended dose, of whom 43 achieved an objective response (93·5%, 95% CI 82·1-98·6) including two complete responses (4·3%, 0·5-14·8) and 41 partial responses (89·1%, 76·4-96·4). Treatment-related adverse events of grade 3 were recorded in 12 (26%) of 46 patients, including two patients each experiencing decreased neutrophil count and increased blood creatine phosphokinase. Serious adverse events occurred in five patients (11%). No grade 4 adverse events or deaths were reported. The study is still ongoing, since 40 of the 46 patients in the phase 2 portion remain on treatment. Interpretation: CH5424802 is well tolerated and highly active in patients with advanced ALK-rearranged NSCLC.
AB - Background: Currently, crizotinib is the only drug that has been approved for treatment of ALK-rearranged non-small-cell lung cancer (NSCLC). We aimed to study the activity and safety of CH5424802, a potent, selective, and orally available ALK inhibitor. Methods: In this multicentre, single-arm, open-label, phase 1-2 study of CH5424802, we recruited ALK inhibitor-naive patients with ALK-rearranged advanced NSCLC from 13 hospitals in Japan. In the phase 1 portion of the study, patients received CH5424802 orally twice daily by dose escalation. The primary endpoints of the phase 1 were dose limiting toxicity (DLT), maximum tolerated dose (MTD), and pharmacokinetic parameters. In the phase 2 portion of the study, patients received CH5424802 at the recommended dose identified in the phase 1 portion of the study orally twice a day. The primary endpoint of the phase 2 was the proportion of patients who had an objective response. Treatment was continued in 21-day cycles until disease progression, intolerable adverse events, or withdrawal of consent. The analysis was done by intent to treat. This study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-101264. Findings: Patients were enrolled between Sept 10, 2010, and April 18, 2012. The data cutoff date was July 31, 2012. In the phase 1 portion, 24 patients were treated at doses of 20-300 mg twice daily. No DLTs or adverse events of grade 4 were noted up to the highest dose; thus 300 mg twice daily was the recommended phase 2 dose. In the phase 2 portion of the study, 46 patients were treated with the recommended dose, of whom 43 achieved an objective response (93·5%, 95% CI 82·1-98·6) including two complete responses (4·3%, 0·5-14·8) and 41 partial responses (89·1%, 76·4-96·4). Treatment-related adverse events of grade 3 were recorded in 12 (26%) of 46 patients, including two patients each experiencing decreased neutrophil count and increased blood creatine phosphokinase. Serious adverse events occurred in five patients (11%). No grade 4 adverse events or deaths were reported. The study is still ongoing, since 40 of the 46 patients in the phase 2 portion remain on treatment. Interpretation: CH5424802 is well tolerated and highly active in patients with advanced ALK-rearranged NSCLC.
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U2 - 10.1016/S1470-2045(13)70142-6
DO - 10.1016/S1470-2045(13)70142-6
M3 - Article
C2 - 23639470
AN - SCOPUS:84878347085
VL - 14
SP - 590
EP - 598
JO - The Lancet Oncology
JF - The Lancet Oncology
SN - 1470-2045
IS - 7
ER -
