title: Phase I study of amatuximab, a novel monoclonal antibody to mesothelin, in Japanese patients with advanced solid tumors.
abstract: 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).
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511, Japan, fujisaka_y@poh.osaka-med.ac.jp.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Fujisaka
authors.forename: Takayasu
authors.initials: T
authors.lastname: Kurata
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tanaka
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kudo
authors.forename: Kunio
authors.initials: K
authors.lastname: Okamoto
authors.forename: Junji
authors.initials: J
authors.lastname: Tsurutani
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kaneda
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Namiki
authors.forename: Chifumi
authors.initials: C
authors.lastname: Kitamura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D000970:Antineoplastic Agents; D044466:Asian People; D004305:Dose-Response Relationship, Drug; D005260:Female; D058851:GPI-Linked Proteins / Q000096:biosynthesis*; D006207:Half-Life; D006801:Humans; D007564:Japan; D008297:Male; D020714:Maximum Tolerated Dose; D000090204:Mesothelin; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D058851:GPI-Linked Proteins; C526187:amatuximab; D000090204:Mesothelin