Phase 1 study of ganitumab (AMG 479), a fully human monoclonal antibody against the insulin-like growth factor receptor type I (IGF1R), in Japanese patients with advanced solid tumors.
OBJECTIVE
This study was to investigate the safety and tolerability of ganitumab in Japanese patients with advanced solid tumors.


METHODS
Patients were enrolled into 1 of 3 dose cohorts (6, 12, or 20 mg/kg) of single-agent ganitumab administered intravenously every 2 weeks. Dose-limiting toxicity (DLT) was assessed for the first 28 days. The primary objectives were to assess the safety, tolerability, and pharmacokinetics (PK) of ganitumab in Japanese patients with advanced solid tumors. An exploratory pharmacodynamic analysis was done to investigate the relationship between exposure and changes in the level of circulating factors in IGF1R pathway (IGFBP-3 and total IGF-1).


RESULTS
Nineteen patients with ECOG performance status 0-1 (6 in cohort 1 and 3, 7 in cohort 2) received at least 1 dose of ganitumab. Median age was 58.0 years. Tumor types included: breast (4), gastric (3), rectal (2), NSCLC (2), thymic (2), and other cancers (6). No DLTs were observed. The most common grade ≥3 adverse events were neutropenia (21 %), leukopenia (16 %) and lymphopenia (11 %). There was a trend of dose-dependency on severity of thrombocytopenia, but not on that of neutropenia. No neutralizing anti-ganitumab antibodies were detected during this study. Dose-linearity on PK of ganitumab was indicated in the dose range. Tumor response was assessed for 19 patients. Stable disease as best response was reported in 7 patients.


CONCLUSIONS
Ganitumab up to 20 mg/kg was tolerable in Japanese patients with advanced solid tumors. The safety and PK profiles were similar to those previously observed in non-Japanese patients.
Shizuoka Cancer Center, Nagaizumi-cho Sunto-gun, Shizuoka, Japan. ha.murakami@scchr.jp
Haruyasu
H
Murakami
Toshihiko
T
Doi
Nobuyuki
N
Yamamoto
Junichiro
J
Watanabe
Narikazu
N
Boku
Nozomu
N
Fuse
Takayuki
T
Yoshino
Atsushi
A
Ohtsu
Satoru
S
Otani
Kazuhiro
K
Shibayama
Takatoshi
T
Takubo
Elwyn
E
Loh
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007564:Japan; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; C545764:ganitumab; D017526:Receptor, IGF Type 1