A phase 1 study of ramucirumab in Japanese patients with advanced solid tumors.
OBJECTIVE
Ramucirumab is a recombinant human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. The aim of this phase 1 study was to evaluate the safety and tolerability of ramucirumab monotherapy in Japanese patients with advanced solid tumors.


METHODS
Patients with solid tumors who had not responded to standard therapy or for whom no standard therapy was available received escalating doses of ramucirumab, administered once every 2 (Q2W) or 3 (Q3W) weeks. The primary objective was to establish the safety and pharmacokinetic profiles of ramucirumab. Secondary and exploratory objectives included assessment of immunogenicity and antitumor activity. ClinicalTrials.gov: NCT01005355.


RESULTS
Fifteen patients were treated with ramucirumab at a dose of 6 mg/kg Q2W (N = 3), 8 mg/kg Q2W (N = 6) or 10 mg/kg Q3W (N = 6). There were no dose-limiting toxicities and the maximum tolerated dose was not reached. The most common ramucirumab-related adverse events were headache, pyrexia, hypertension and increased aspartate aminotransferase. Following single-dose administration of ramucirumab, there appeared to be a dose-proportional increase in maximum observed drug concentration but not in area under the curve. Treatment-emergent anti-ramucirumab antibodies were not detected in any patient.


CONCLUSIONS
Ramucirumab monotherapy was well tolerated and feasible at the doses and schedules used in this study population of Japanese patients with advanced solid tumors.
National Cancer Center Hospital, Tokyo, Japan.
Hiroshi
H
Nokihara
National Cancer Center Hospital, Tokyo, Japan.
Noboru
N
Yamamoto
National Cancer Center Hospital, Tokyo, Japan.
Yasuhide
Y
Yamada
National Cancer Center Hospital, Tokyo, Japan.|Present address: Aichi Cancer Center Hospital, Nagoya, Japan.
Kazunori
K
Honda
National Cancer Center Hospital, Tokyo, Japan.|Present address: Hokkaido University Hospital, Sapporo, Japan.
Hajime
H
Asahina
National Cancer Center Hospital, Tokyo, Japan.|Present address: Osaka Medical College Hospital, Osaka, Japan.
Yosuke
Y
Tamura
Eli Lilly and Company, Indianapolis, IN, USA.
Rebecca R
RR
Hozak
Eli Lilly and Company, Bridgewater, NJ, USA.
Ling
L
Gao
Eli Lilly Japan, Kobe, Japan.
Kazumi
K
Suzukawa
Eli Lilly Japan, Kobe, Japan.
Sotaro
S
Enatsu
National Cancer Center Hospital, Tokyo, Japan.|Present address: St Luke's International Hospital, Tokyo, Japan.
Tomohide
T
Tamura
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D000096662:Ramucirumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D000096662:Ramucirumab
antibodies; clinical trial; monoclonal; phase I; ramucirumab; receptors; solid tumor; vascular endothelial growth factor