Phase I study of amatuximab, a novel monoclonal antibody to mesothelin, in Japanese patients with advanced solid tumors

• Published in: Investigational new drugs Vol. 33; no. 2; pp. 380 - 388
• Main Authors: Fujisaka, Yasuhito, Kurata, Takayasu, Tanaka, Kaoru, Kudo, Toshihiro, Okamoto, Kunio, Tsurutani, Junji, Kaneda, Hiroyasu, Okamoto, Isamu, Namiki, Masayuki, Kitamura, Chifumi, Nakagawa, Kazuhiko
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.04.2015; Springer Nature B.V
• Subjects: Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - pharmacology; Antineoplastic Agents; Asian Continental Ancestry Group; Blood; Cancer therapies; Chemotherapy; Clinical trials; Dose-Response Relationship, Drug; Drug dosages; Drug therapy; Female; GPI-Linked Proteins - biosynthesis; Half-Life; Hepatitis; Hospitals; Humans; Japan; Leukopenia; Male; Maximum Tolerated Dose; Medicine; Medicine & Public Health; Mesothelioma; Metabolic Clearance Rate; Metastasis; Middle Aged; Monoclonal antibodies; Neoplasms - drug therapy; Neutropenia; Oncology; Ovarian cancer; Patients; Pharmacokinetics; Pharmacology/Toxicology; Phase I Studies; Statistical analysis; Toxicity; Tumors; Japan; Mesothelin; Phase I study; MORAb-009; Antibody; Amatuximab
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-014-0196-0

Summary Amatuximab is a chimeric monoclonal antibody that targets mesothelin, which is expressed in virtually all mesotheliomas and pancreatic adenocarcinomas. The objective of this study was to determine the dose-limiting toxicity and the maximum tolerated dose. Patients with mesothelioma, pancreatic adenocarcinoma or other mesothelin-positive solid tumors were eligible for this study. Amatuximab was administered weekly as an intravenous infusion in 4-week cycles at progressively increasing doses ranging from 50 to 200 mg/m 2 . Seventeen patients received amatuximab. Two dose-limiting toxicities were observed: one at 50 mg/m 2 and one at 200 mg/m 2 ; the maximum tolerated dose of this study was determined to be 200 mg/m 2 . Of the 17 patients, 13 patients (76.5 %) experienced treatment-related adverse events. The most common adverse events were grade 1 fatigue (29.4 %) and pyrexia (23.5 %). The maximum serum concentration and area under the concentration curve values increased in an almost dose-proportional manner. Three patients had stable disease. Amatuximab was generally well tolerated at doses up to 200 mg/m 2 . The pharmacokinetic profile of amatuximab in the Japanese population was similar to that seen in the United States population (Clinical Trials.gov Identifier: NCT01018784).