Clinical Research Papers:

Safety and pharmacokinetics of DS-6051b in Japanese patients with non-small cell lung cancer harboring ROS1 fusions: a phase I study

Yutaka Fujiwara _, Masayuki Takeda, Noboru Yamamoto, Kazuhiko Nakagawa, Kaname Nosaki, Ryo Toyozawa, Chihiro Abe, Ryota Shiga, Kenji Nakamaru and Takashi Seto

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Oncotarget. 2018; 9:23729-23737. https://doi.org/10.18632/oncotarget.25263

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Yutaka Fujiwara1, Masayuki Takeda2, Noboru Yamamoto1, Kazuhiko Nakagawa2, Kaname Nosaki3, Ryo Toyozawa3, Chihiro Abe4, Ryota Shiga4, Kenji Nakamaru4 and Takashi Seto3

1Department of Experimental Therapeutics, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan

2Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama-shi, Osaka 589-8511, Japan

3Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Minami-ku, Fukuoka-shi, Fukuoka 811-1395, Japan

4Daiichi Sankyo Co., Ltd., Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan

Correspondence to:

Yutaka Fujiwara, email: [email protected]

Keywords: DS-6051b; non-small cell lung cancer; ROS1; pharmacokinetics; Japanese

Received: December 19, 2017     Accepted: April 06, 2018     Published: May 04, 2018


Oncogenic ROS1 and NTRK fusions were reported in solid tumors, including non-small cell lung cancer (NSCLC). DS-6051b is an oral, potent selective small molecule tyrosine kinase inhibitor. We report the safety, tolerability, efficacy, and pharmacokinetics of DS-6051b in 15 Japanese patients with NSCLC harboring ROS1 fusions. Patients received DS-6051b once daily (400 mg n = 6; 600 mg n = 6; or 800 mg n = 3) for cycles of 3 weeks. Safety, tolerability, maximum-tolerated dose, pharmacokinetics, and recommended dose for phase II were determined. Common treatment-related adverse events were increased: aspartate aminotransferase and alanine aminotransferase (80.0% each), diarrhea (53.3%), and nausea (46.7%). Dose-limiting toxicities (two grade-3 alanine aminotransferase increases) were seen in the 800 mg cohort. The maximum-tolerated dose and recommended phase II dose was 600 mg once daily. Plasma concentrations of free DS-6051b and DS-6051a increased with dose. Compared with a US phase I study, AUC0–24 h on day 15 was higher but narrowed after body weight correction. Objective response rate was 58.3% in patients with target lesions (n = 12) and 66.7% in crizotinib-naïve patients (n = 9). Disease control rate was 100%. DS-6051b is well tolerated and effective in Japanese patients with NSCLC harboring ROS1 fusions and might be a targeted therapy for advanced NSCLC.

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