CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): A single-arm, open-label, phase 1-2 study

Takashi Seto, Katsuyuki Kiura, Makoto Nishio, Kazuhiko Nakagawa, Makoto Maemondo, Akira Inoue, Toyoaki Hida, Nobuyuki Yamamoto, Hiroshige Yoshioka, Masao Harada, Yuichiro Ohe, Naoyuki Nogami, Kengo Takeuchi, Tadashi Shimada, Tomohiro Tanaka, Tomohide Tamura

Research output: Contribution to journalArticle

413 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)590-598
Number of pages9
JournalThe Lancet Oncology
Volume14
Issue number7
DOIs
Publication statusPublished - Jun 2013

Fingerprint

Non-Small Cell Lung Carcinoma
CH5424802
Japan
Information Centers
Cancer Care Facilities
Maximum Tolerated Dose
Therapeutics
Creatine Kinase
Pharmaceutical Preparations
Disease Progression
Neutrophils
Pharmacokinetics
Safety

ASJC Scopus subject areas

  • Oncology

Cite this

CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study) : A single-arm, open-label, phase 1-2 study. / Seto, Takashi; Kiura, Katsuyuki; Nishio, Makoto; Nakagawa, Kazuhiko; Maemondo, Makoto; Inoue, Akira; Hida, Toyoaki; Yamamoto, Nobuyuki; Yoshioka, Hiroshige; Harada, Masao; Ohe, Yuichiro; Nogami, Naoyuki; Takeuchi, Kengo; Shimada, Tadashi; Tanaka, Tomohiro; Tamura, Tomohide.

In: The Lancet Oncology, Vol. 14, No. 7, 06.2013, p. 590-598.

Research output: Contribution to journalArticle

Seto, T, Kiura, K, Nishio, M, Nakagawa, K, Maemondo, M, Inoue, A, Hida, T, Yamamoto, N, Yoshioka, H, Harada, M, Ohe, Y, Nogami, N, Takeuchi, K, Shimada, T, Tanaka, T & Tamura, T 2013, 'CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): A single-arm, open-label, phase 1-2 study', The Lancet Oncology, vol. 14, no. 7, pp. 590-598. https://doi.org/10.1016/S1470-2045(13)70142-6
Seto, Takashi ; Kiura, Katsuyuki ; Nishio, Makoto ; Nakagawa, Kazuhiko ; Maemondo, Makoto ; Inoue, Akira ; Hida, Toyoaki ; Yamamoto, Nobuyuki ; Yoshioka, Hiroshige ; Harada, Masao ; Ohe, Yuichiro ; Nogami, Naoyuki ; Takeuchi, Kengo ; Shimada, Tadashi ; Tanaka, Tomohiro ; Tamura, Tomohide. / CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study) : A single-arm, open-label, phase 1-2 study. In: The Lancet Oncology. 2013 ; Vol. 14, No. 7. pp. 590-598.
@article{d83e3e36a7c045feb53124834c85007a,
title = "CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): A single-arm, open-label, phase 1-2 study",
abstract = "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.",
author = "Takashi Seto and Katsuyuki Kiura and Makoto Nishio and Kazuhiko Nakagawa and Makoto Maemondo and Akira Inoue and Toyoaki Hida and Nobuyuki Yamamoto and Hiroshige Yoshioka and Masao Harada and Yuichiro Ohe and Naoyuki Nogami and Kengo Takeuchi and Tadashi Shimada and Tomohiro Tanaka and Tomohide Tamura",
year = "2013",
month = "6",
doi = "10.1016/S1470-2045(13)70142-6",
language = "English",
volume = "14",
pages = "590--598",
journal = "The Lancet Oncology",
issn = "1470-2045",
publisher = "Lancet Publishing Group",
number = "7",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=84878347085&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878347085&partnerID=8YFLogxK

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 -