Phase 1 study of the investigational, oral angiogenesis inhibitor motesanib in Japanese patients with advanced solid tumors.
OBJECTIVE
The aim of this study was to investigate the safety and pharmacokinetics of motesanib (AMG 706), a small-molecule antagonist of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptor, and c-Kit in Japanese patients with advanced solid tumors.


METHODS
Patients were administered motesanib orally once daily (QD) at doses of 50, 100, and 125 mg QD. The total study duration for each patient consisted of three cycles of 28 days per cycle. The primary endpoints were the incidence of dose-limiting toxicities (DLTs), estimation of the maximum tolerated dose (MTD), and assessment of pharmacokinetic parameters of motesanib.


RESULTS
Fifteen patients were enrolled and received motesanib. No DLTs were observed and, therefore, the MTD was not reached. Motesanib had acceptable toxicity at doses up to 125 mg QD. The pharmacokinetics of motesanib appears to be dose proportional. No objective responses per RECIST were observed. However, all 15 patients achieved stable disease, and five patients had durable (>24 weeks) stable disease.


CONCLUSIONS
The results of this study demonstrate that motesanib is tolerable in Japanese patients at doses up to 125 mg QD.
Fujisaka
Yasuhito
Y
Division of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan. yfujisaka@gmail.com
Yamada
Yasuhide
Y
Yamamoto
Noboru
N
Shimizu
Toshio
T
Fujiwara
Yutaka
Y
Yamada
Kazuhiko
K
Tamura
Tomohide
T
Watanabe
Hiroyuki
H
Sun
Yu-Nien
YN
Bass
Michael B
MB
Seki
Mitsuo
M
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D007564:Japan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009841:Oligonucleotides; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007211:Indoles; D009841:Oligonucleotides; D009536:Niacinamide; C519562:imetelstat