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
| Autor: | Takatoshi Takubo, Elwyn Loh, Kazuhiro Shibayama, Nozomu Fuse, Junichiro Watanabe, Takayuki Yoshino, Nobuyuki Yamamoto, Satoru Otani, Toshihiko Doi, Atsushi Ohtsu, Narikazu Boku, Haruyasu Murakami |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty medicine.drug_class Antineoplastic Agents Insulin-Like Growth Factor Receptor Antibodies Monoclonal Humanized Toxicology Monoclonal antibody Receptor IGF Type 1 Asian People Japan Clinical trial phase 1 Neoplasms Internal medicine medicine Humans Pharmacology (medical) Insulin-Like Growth Factor I Ganitumab Receptor Aged Insulin-like growth factor 1 receptor Pharmacology Dose-Response Relationship Drug biology business.industry Antibodies Monoclonal Middle Aged Gemcitabine Insulin-Like Growth Factor Binding Protein 3 Treatment Outcome Endocrinology Oncology Tolerability Insulin-like growth factor receptor type 1 Monoclonal Cancer research biology.protein Female Original Article Antibody business medicine.drug |
| Zdroj: | Cancer Chemotherapy and Pharmacology |
| ISSN: | 1432-0843 0344-5704 |
| DOI: | 10.1007/s00280-012-1924-9 |
| Popis: | Purpose 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. |
| Databáze: | OpenAIRE |
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